Does DNA evidence refute the Book of Mormon?
Appendix 2: Understanding the Scientific Evidence
This page supports my main Mormon Answers page on DNA Evidence and the Book of Mormon. Here I get into specific scientific issues for those seeking to understand this topic, reviewing a variety of scientific studies and getting into some specific technical issues. This work is my responsibility and does not necessarily reflect official views of the Church. Copyright © 2002-2013 by Jeff Lindsay.
The recent ability of scientists to determine the structure of human DNA has created an explosion of research involving genetics, disease, evolution, and the origins of human population groups. The study of human origins is facilitated by analysis of DNA that is spared the complexity of the recombination. While most genes can come from either parent, such that the DNA from the parents is recombined in the child, some parts of human DNA are free from recombination. The mitochondria, small energy-producing structures in our cells, contain special DNA that is inherited only from the mother, without recombination with the DNA of the father. Analysis of mitochondrial DNA (mtDNA) shows DNA structures that have been passed along purely maternal lines, from mother to daughter over the generations. Such analysis has proven to be a useful tool for many purposes (Richards and Macaulay, 2001). Likewise, the Y chromosome in men is passed along paternal lines only. Analysis of Y chromosomes can be used to link modern humans to male ancestors. Both mtDNA and Y chromosomes are subject to mutations that occur rarely but with presumably constant rates (the rates depend on what portion of the DNA is being examined--some portions mutate frequently, others remain very steady over time). Groups that share many common mutations can be presumed to be closely related. Groups that have very few common mutations may be presumed to come from family lines that diverged long ago.
The typical human mtDNA molecule is a circular molecule comprising 16569 nucleotides in a specific order. These nucleotides, adenine, guanine, cytosine, and thymine are labeled A, G, C, and T, respectively. An arbitrary position has been defined as nucleotide 1. A standard mtDNA sequence, known as the Cambridge Reference, was the first published human mtDNA sequence (S. Anderson et al., 1981). Mutations can result in a variety of changes, such as a substitution of one nucleotide for another, a deletion of a part of the sequence, or the addition of one or more nucleotides.
Several tools are used in DNA studies. Restriction Fragment Length Polymorphism (RFLP) classified DNA by analysis of patterns in DNA that has been cleaved into chunks by enzymes (restriction endonuclease). If two organisms differ in the distance between sites of cleavage achieved with a particular enzyme, the length of the fragments produced by enzymatic attack will differ. The similarity of the patterns generated can be used to distinguish species. Recent studies employ up to 14 different enzymes that can provide high resolution of differences in portions of human DNA. RFLP is often applied to a highly variable portion of non-coding DNA in the mitochondria called either the control region (CR) or the D-loop.
Direct sequencing of portions of human DNA yields series of nucleotides that allow direct comparison of various genes with those of different individuals. The extensive sequence information can be used to map groups of related individuals into clusters or clades.
Genetic analysis can also be done looking at proteins in the blood, the presence of certain genetic diseases or other genetic traits, and so forth.
Evidence for Asian Origins and Arguments against the Book of Mormon
Studies in the 1980s based on analysis of linguistic, dental, and genetic evidence resulted in the hypothesis that there were three genetic groups in the Americas, the Amerinds, the Na-Denes, and the Aleut-Eskimos, apparently due to three separate migrations of ancestral Asian populations across the Bering Strait. Greenberg et al. (1986) suggested that the first migration (beginning 12,000 years ago) eventually resulted in the spread of Amerind-speakers throughout North, Central, and South America, followed by additional migrations that brought the ancestors of the NaDene-speakers and Aleut-Eskimo speakers into the northern part of the continent. Other early genetic studies supported the three-wave model, while mtDNA studies have pointed to as many as four major waves of migration. But in 1995, a commonly-cited study by Merriwether et al. (1995) argued for a single migration from Mongolia or northern China, based on their review of mtDNA evidence. (See also Kolman et al., 1996.)
A critical fact is that the dominant mtDNA haplogroups in the New World, called haplogroups A, B, C, and D, could all be found in Asia and could very well have originated there. Some have argued that only one migration of a founder population could give rise to all four haplogroups in the New World.
The single-migration view is being eroded in the wake of additional recent studies pointing to multiple migrations. An excellent but very brief summary of recent developments in this area is given by Dillehay (2003 - available online), who notes the growing evidence for multiple migrations (from various Asia and the Pacific rim) and concludes by saying, "Slowly, we are realizing that the ancestry of the Americas is as complex and as difficult to trace as that of other human lineages around the world."
Among genetic studies that challenge single-migration views, Karafet et al. (1999) studied Y-chromosome markers from over 2000 DNA samples from around the world, including 62 Inuit Eskimos, 12 Mixe, 29 Mixtecs, 22 Kazakhs, 30 Evenks, 18 Melanesians, and 54 samples from several tribes in Panama. Fifteen indigenous North Asian groups were also included. Based on analysis of the 95 haplotypes they identified, the authors concluded that there were multiple founder haplotypes that entered the Americas, including the possibility of multiple migrations from a region in Siberia.
In addition to citing Merriwether et al. (1995) to support a single Asiatic migration, Book of Mormon critics are regularly citing a recent article by F.R. Santos et al., "The Central Siberian Origin for Native American Y Chromosomes," American Journal of Human Genetics, Vol. 64, 1999, pp. 619-628, as evidence that the Book of Mormon is wrong. Some of them like this study so much that they have plagiarized the entire article on their Web pages. No need to use a plagiarized copy; use the legal electronic full-text version of Santos et al. (1999) at http://www.cell.com/AJHG/fulltext/S0002-9297(07)61769-8 (better yet, use the PDF version).
The study of Santos et al. (1999) was conducted with a worldwide sample of 306 men. The major Y haplogroup present in most (not all) Native Americans suggested common ancestry with some Siberians, especially the Kets and Altaians from the Yanissey River Basin and the Altai Mountains, respectively. As we will see, this region appears to be one of the best candidates for a major source of New World genes, though other studies point to other parts of Asia.
As always, though, the scope of the study included only a small number of individuals. The 306 men included only a minute sampling of New World genes:
Ten samples, from south and central Amerindians and a Nadene, were purchased from the National Institute of General Medical Science, and an additional 10 Native American samples (not Aleut-Eskimo) came from paternity tests in North America. (p. 620)
Rare haplotypes are not likely to be found with such small sample sizes. The study does not and cannot purport to explain the origins of ALL Native Americans or to rule out limited infusion from the Middle East long after 10,000 B.C. But it does provide a plausible case that most Native Americans share common ancestry with some Siberians. The DNA evidence alone, however, does not explain which group migrated where, when, or how--but based on geologic and other evidence, it is reasonable to assume a Bering Strait migration from Asia occurred.
However, the text of Santos et al. (1999) is not nearly so harmful to the Book of Mormon as critics would have us believe. In fact, Santos et al. (1999) provides evidence that the principal ancestors of Native Americans may have Caucasian ties, though much more ancient than would fit the Book of Mormon text, if we accept the accuracy of the evolutionary dating methods used. Let's consider several excerpts from this study:
In all the trees, the Native American Y chromosomes clustered with Kets, Altaians, and Caucasoids (Europeans and Indians). European admixture cannot explain this cluster, because if we exclude in the analysis all haplotypes present in Siberians and Amerindians that are also found in Europe (such as haplotype 1, which appears in four Native Americans), the tree remains very similar. . . . (p. 624)
Although some Siberian and Native American Y chromosomes show remarkably close association with Caucasoid Y chromosomes, other Siberian populations are very distinct, clustering with other Asians. . . . (p. 624)
In addition, these data identify the group of Ket and Altaian Y chromosomes that are related to those among Native Americans and Caucasoids, whereas the Evenki Y chromosomes are related to those of Mongolians. . . . (p. 625)
The major Native American haplotype 31 is present on both sides of Beringia, most likely because of an American or Beringian origin of the mutation in the DYS199 locus (Karafet et al. 1997; Lell et al. 1997). Its immediate ancestor, haplotype 10, is a rare haplotype (11 of 306 individuals) seen only in North America (n = 6), India (n = 4), and Mongolia (n = 1). An old population bearing haplotype 10, a Native American/Siberian/Caucasoid common ancestor, has been placed somewhere in central Eurasia . Haplotypes 1 (Caucasoid), 20 (Siberian and Native American), and 31 (Native American) are derived from this ancestor. The most common European chromosome, haplotype 1, appeared in four Native American samples from paternity tests in North America; thus, they very likely could be due to recent admixture. Haplotype 20, another descendant of haplotype 10 by a simple alphoid locus deletion step, is very frequent in Kets and was found in some Altaians, all of whom were shown to also have the DYS19 A allele (data not shown), which is also present in most individuals with haplotype 31 (Pena et al. 1995; Santos et al. 1995a; Underhill et al. 1996). Recently, the Ket language was suggested to be closely related to the Na-Dene language (Greenberg 1996), and the resemblance of Kets to Native Americans and Caucasoids, with regard to physical appearance (Forsyth 1996) and Y chromosomes (this study), makes them the most likely central Siberian population to share the same recent ancestors. The Altaians, a common denomination for seven formerly distinct Turkic populations, exhibit very diverse Y haplotypes and could have acquired their Y chromosomes from many neighboring tribes, including the Kets (Forsyth 1996). . . . (p. 626, emphasis mine, references to a table and a figure deleted)
The very recent find of the 9,400-year-old skeleton of the Kennewick man, which displays some Caucasoid characteristics, and his contemporary, the Spirit Cave mummy, suggests that the earliest migrants could be distinct from present-day populations (Morell 1998b). Possible genetic relationships between Eurasians and Native Americans are suggested by the presence of the rare mtDNA haplogroup X in both population groups, which apparently is absent in Siberia (Morell 1998a). Alternatively, in our study, the Y chromosome data reveal a common ancestor (haplotype 10) between Native Americans and Europeans, who left some rare descendants in Siberia, among the Kets and Altaians. However, the presence of the most common European haplotype 1 in the Americas can be explained as a recent European admixture more likely than as a remnant of a pre-Columbian migrant. Our Y chromosome data, when compared with morphological and mtDNA data, could imply another migration of typically Mongoloid people, who would have left phenotypic traces in their Native American descendants without contributing many of their Y chromosomes. This pattern of unequal paternal and maternal contributions in the gene pools of several populations has been characterized and discussed in detail by Poloni et al. [E.S. Poloni, Amer. J. Human Genetics, 61: 1015-1035 (1997)]. (p. 626, references to a table deleted)
This study traces the major Native American Y chromosome haplotype to the immediate ancestor shared with present-day Siberians and to an older common ancestor shared with Caucasoids (Europeans and Indians). This common ancestry of Native Americans and Caucasoids could explain the existence of non-Mongoloid skeletons, such as the Kennewick man. (p. 627, emphasis mine)
The authors estimate that first migrants with a proto-Caucasoid Y chromosome entered the New World 30,000 years ago. Of course, the date of entry of these European-related genes is long before Book of Mormon times, if the assumptions behind the dating are correct. Interestingly, the scenario painted here is not one of typical Asians migrating across the Bering Strait, but of a clan with roots in Central Asia who migrated across Asia, leaving little trace except for a few descendants among the Kets and Altaians. And given the diversity of Y chromosomes among the Altaians, the authors speculate that they may have obtained their Y chromosomes from other groups, such as the Kets.
The authors argue against a single migration (p. 627), and speak of multiple minor migrations that would have brought the more recent Na-Dene and Eskimo-Aleut groups (p. 626).
Thus, one of the major studies used to supposedly shut the coffin on the Book of Mormon points to ancient genetic ties to Europe and Central Asia, and supports the possibility of multiple migrations to the New World. The dating of the first major migration, though, does not relate to Book of Mormon peoples.
Many other studies yield similar conclusions, including those showing that most Native Americans fall within one of four major haplogroups, A, B, C, or D, groups which are also typical of Asia. For several years, the mtDNA results appeared to raise insurmountable barriers for some people's understanding of the Book of Mormon. Four major haplogroups dominated the New World, and they all appeared to come from Asia, not the Middle East. It even appears that a few people left the Church because their testimonies were so shaken. Why were there no genetic markers linking modern "Lamanites" with the ancient Middle East?
Then followed an important new development in the mtDNA analysis. Early conclusions had to be revisited in light of new evidence, for there was actually a fifth haplogroup that had been found in several Native American populations, a haplogroup that was not known to exist in Asia but which WAS found throughout Europe and the Middle East, including Israel. This fifth haplogroup was termed the "X haplogroup" (though Parr et al., 1996, speak of a "haplotype N" found in ancient DNA in Fremont Amerindians, which I believe was actually haplotype X). Key studies exploring its implications for New World origins include those of Brown et al. (1998) and Forster et al. (1996).
Virginia Morell (1998) provided some of the early publicity on haplogroup X in an article in the widely read journal Science. Here are a few excerpts:
Anthropologists have long assumed that the first Americans, who crossed into North America by way of the Bering Strait, were originally of Asian stock. But recently they have been puzzled by surprising features on a handful of ancient American skeletons, including the controversial one known as Kennewick Man--features that resemble those of Europeans rather than Asians (Science, 10 April 1998, p. 190). Now a new genetic study may link Native Americans and people of Europe and the Middle East, offering tantalizing support to a controversial theory that a band of people who originally lived in Europe or Asia Minor were among the continent's first settlers.
The new data, from a genetic marker appropriately called Lineage X, suggest a "definite--if ancient--link between Eurasians and Native Americans," says Theodore Schurr, a molecular anthropologist from Emory University in Atlanta, who presented the findings earlier this month at the annual meeting of the American Association of Physical Anthropologists in Salt Lake City....
The team, led by Emory researchers Michael Brown and Douglas Wallace, and including Antonio Torroni from the University of Rome and Hans-Jurgen Bandelt from the University of Hamburg in Germany, was searching for the source population of a puzzling marker known as X. This marker is found at low frequencies throughout modern Native Americans and has also turned up in the remains of ancient Americans. Identified as a unique suite of genetic variations, X is found on the DNA in the cellular organelle called the mitochondrion, which is inherited only from the mother.
Researchers had already identified four common genetic variants, called haplogroups A, B, C, and D, in the mitochondrial DNA (mtDNA) of living Native Americans (Science, 4 October 1996, p. 31). These haplogroups turned up in various Asian populations, lending genetic support for the leading theory that Native Americans descended primarily from these peoples. But researchers also found a handful of other less common variants, one of which was later identified as X.
Haplogroup X was different. It was spotted by Torroni in a small number of European populations. So the Emory group set out to explore the marker's source. They analyzed blood samples from Native American, European, and Asian populations and reviewed published studies. "We fully expected to find it in Asia," like the other four Native American markers, says Brown.
To their surprise, however, haplogroup X was only confirmed in the genes of a smattering of living people in Europe and Asia Minor, including Italians, Finns, and certain Israelis. The team's review of published mtDNA sequences suggests that it may also be in Turks, Bulgarians, and Spaniards. But Brown's search has yet to find haplogroup X in any Asian population. "It's not in Tibet, Mongolia, Southeast Asia, or Northeast Asia," Schurr told the meeting. "The only time you pick it up is when you move west into Eurasia." (emphasis mine)
Haplogroup X is found in several places outside of Asia, including among the Finns, for example (Finnila et al., 2001), who are often thought to be an outlier group in Europe in light of Y chromosome studies, but nevertheless appear to share many mtDNA lineages with other Europeans. Detailed information about the mutations separating the X haplogroup from the Cambridge Reference and other European haplogroups are provided by Finnila et al. (2001)--especially see their Figure 2.
A related article is on the Web: "Europeans Colonised America in 28,000 BC" by Roger Highfield (2000), Science Editor for Britain's Electronic Telegraph news service. Here's an excerpt:
The find has led to some speculation that ancient people crossed the Atlantic from the Old World, because evidence of the group has not so far been found in Asia, though [Schurr] stressed that not all central Asian groups had been analysed. Dr Schurr said: "Haplogroup X was brought to the New World by an ancient Eurasian population in a migratory event distinct from those bringing the other four lineages to the Americas."
The haplogroup X occurs most among Algonkian-speaking groups such as the Ojibwa [sometimes spelled Ojibwe], and has been detected in two pre-Colombian north American populations. Today, haplogroup X is found in between two and four per cent of European populations, and in the Middle East, he said, particularly in Israel. (emphasis mine)
Schurr (2000) points to other evidence of haplotype X in "two Pre-Columbian North American populations" and possibly "a few ancient Brazilian samples." He may be referring to the work of Ribero-dos-Santos et al. (1996), as later clarified (Ribero-dos-Santos et al., 1997).
Now even if haplogroup X could be shown to come from Israel, that would not prove the Book of Mormon to be true. The haplogroup X which links "certain Israelis" and Europeans with Native Americans may have no relation to the Nephites, the Jaredites, or the Mulekites. Indeed, their estimated arrival date is about 10,000 B.C. or earlier, too early to be related directly to Book of Mormon history, if the assumptions behind the dating are correct. But this new study perhaps strengthens the possibility of ancient migrations from the Middle East to the Americas, a possibility that has long been denied by Book of Mormon critics and others.
In discussing haplogroup X and Native American origins, Dr. Theodore G. Schurr (2000) reviews the wide diversity of Native American genotypes and provides many intriguing photographs showing great diversity. He demonstrates that the distribution of mitochondrial DNA (mtDNA) groups in the New World is much more complicated than previously thought, and cannot be explained solely by Siberian genes arriving via the Bering Strait. Schurr estimates haplogroup X has been on this continent for 13,000 to 35,000 years (though I would suggest that a recent migrant group already having a diversity of haplogroup mutations could bring new DNA that appears old). He also discusses other haplogroups, such as H, T, J, and L. Not enough work has been done yet to clearly determine whether these are all due to mixing with Old World peoples since the time of Columbus, or whether these haplogroups were present more anciently.
In spite of the problem with the dating of haplogroup X, several Latter-day Saints, including myself, were excited by the fact that it was found in Israel but NOT anywhere in Asia, suggesting that Siberia-only theories of Native American origins were simply wrong. This changed in 2001.
The lack of the haplogroup X in Siberia posed a problem for "Siberia only" theories of Native American origins--until it was discovered among the Altai people, a minuscule group in south western Siberia. Derenko (2001) reports the discovery and the implications for New World settling. The Altaians, the only group in Asia of many studied now known to have haplogroup X, live in Southern Siberia and comprise 60,000 people divided between seven formerly distinct Turkic-speaking groups: the Altai-Kizhi, Teleuts, and Telenghits (these three are southern Altaians), and the Chelkans, Kumandins, Tubalars, and Maimalars (these four are the northern Altaians). Southern Altaians are said to be typical central Asian Mongoloids, from the viewpoint of anthropology, while "the northern Altaians exhibit some Caucasoid anthropological features" (Derenko, p. 240). According to Derenko et al., over 3% of Altaians have haplogroup X. Its presence cannot be explained by recent admixture with Russians, among whom haplogroup X occurs at very low levels (3 out of 336 subjects tested). (Though unlikely, one could imagine that admixture could have occurred with a group of Russians rich in haplogroup X.) The Altaians not only have haplogroup X, but like many other Asian populations, have the other 4 mtDNA haplogroups that dominate indigenous New World peoples: A, B, C, and D. Thus, one can consider the ancestors of the Altaians as a candidate that could account for New World haplogroups, especially for haplogroup X.
Derenko et al. (2001) imply that the discovery of haplogroup X resolves many questions about Native American origins, stating that, "It is obvious that we have now the genetic evidence that will allow closer determination of which Siberian population was the source of the population expansion leading to modern American Indians. . . ." (p. 240)
But are the Altaians directly tied to Native Americans? The species of haplogroup X found among the Altaians is different than that found in the New World. Derenko's mapping of the relationships based on mutations between various European, New World, and Altaians X haplotypes shows distinct differences. None of the Altaian X mtDNAs had a mutation called the 225A variant, whereas Brown et al. (1998) identify the 225A variant as a major marker for the X haplogroup. In Brown's study, 11 of 22 Native Americans with X mtDNA had the 225A variant, which is also commonly associated with European X mtDNA. Brown et al. (1998) report that the nucleotide at position 225 "appears to be stable, since this variant [225A] has never been seen in populations from Asia, Central and South America, or Africa" (p. 1855, citations deleted). And it has still not been seen among the Altaians. It is true that Native American X mtDNA differs with respect to typical European X mtDNA in some ways, but without the 225A variant among the Altaians, we need not accept the Altaians as the sole source of X mtDNA in the New World.
As discussed above, discovery of haplogroup X in an isolated, tiny group in Asia does not answer many questions. Does the presence of haplogroup X in Siberia really mean that the Altaians crossed the Bering Strait--leaving no trace along their Asian route? Out of all the peoples that could have crossed the Bering Strait, many of whom were closer than the Altaians, why did just this one small group become the alleged primary founders of New World? Isn't it just as likely that a group of Native Americans, X haplotypes and all, migrated into the Old World to join the ancestors of the Altaians? Or couldn't the Altaians, with their ties to Turkic languages, have ancestors that came from the Middle East, bringing their X haplotypes with them?
The discovery of X mtDNA among the Altaians is tantalizing evidence of--well, something. It does not answer many questions or explain the source of the 225A variant in the New World. But there could be a connection that merits further attention.
Brown's work (1998) also suggested that Native American haplotype X mtDNA differed from Old World haplotype X DNA with respect to nucleotide position 16213, but new information on this issue comes from Malhi et al. (2002):
Brown et al. (1998) demonstrated that Europeans assigned to haplogroup X lack a mutation at np 16213 in the HVSI [hypervariable segment I] that all Native Americans exhibit. However, the larger sample size of individuals assigned to haplogroup X in the present study reveals that a substantial number of Native Americans in multiple geographic regions also lack the np 16213G mutation and therefore have haplotypes identical to those of European (Brown et al. 1998) and Asian (Derenko et al. 2001) members of haplogroup X.
Thus, at least with regard to the mutation at np 16213, it is possible that Native American haplotype X mtDNA could have Asian or European origins (which need not rule out entry by Jewish ancestors).
Nov. 2003 Update: The recent work of Reidla et al. (2003) confirms the statements above indicating that the haplogroup X DNA in the Americas is not directly related to the unusual little pocket haplogroup X DNA in Siberia (the Altai region). In fact, their study of X DNA is consistent with the idea that the general region of the Middle East (West Eurasia) ultimately could have been the source of the haplogroup X DNA found in the Americas, though they give dates (based on standard dating assumptions) that are many thousands of years too early to explain haplogroup X in the Americas by an appeal to the Book of Mormon. According to Reidla et al.:
The results of this study point to the following conclusions. First, haplogroup X variation is completely captured by two ancient clades that display distinctive phylogeographic patterns--X1 is largely restricted to North and East Africa, whereas X2 is spread widely throughout West Eurasia. Second, it is apparent that the Native American haplogroup X mtDNAs derive from X2 by a unique combination of five mutations. Third, the few Altaian (Derenko et al. 2001) and Siberian haplogroup X lineages are not related to the Native American cluster, and they are more likely explained by recent gene flow from Europe or from West Asia. [emphasis mine]
Here is the abstract for Reidla et al. (2003):
A maximum parsimony tree of 21 complete mitochondrial DNA (mtDNA) sequences belonging to haplogroup X and the survey of the haplogroup-associated polymorphisms in 13,589 mtDNAs from Eurasia and Africa revealed that haplogroup X is subdivided into two major branches, here defined as "X1" and "X2." The first is restricted to the populations of North and East Africa and the Near East, whereas X2 encompasses all X mtDNAs from Europe, western and Central Asia, Siberia, and the great majority of the Near East, as well as some North African samples. Subhaplogroup X1 diversity indicates an early coalescence time, whereas X2 has apparently undergone a more recent population expansion in Eurasia, most likely around or after the last glacial maximum. It is notable that X2 includes the two complete Native American X sequences that constitute the distinctive X2a clade, a clade that lacks close relatives in the entire Old World, including Siberia. The position of X2a in the phylogenetic tree suggests an early split from the other X2 clades, likely at the very beginning of their expansion and spread from the Near East.
Interestingly, a search of Reidla et al.'s dataset for Old World matches for some of the five unique mutations defining the North American haplotype X clade X2a found a match for only one of the mutations and that came from Iran. This may point to the Near East as the source for a common ancestor for Native American haplotype X mtDNA, but the authors suggest that the match is more likely due to recurrence of mutations rather than common origins:
The Native American-specific clade X2a appears to be defined by five mutations, three in the coding region (8913, 12397, and 14502) and two in the control region (200 and 16213) (fig. 1). The transition at np 200 was seen in virtually all previously analyzed Native American haplogroup X mtDNAs, whereas the transition at np 16213 was absent in some of the Ojibwa described by Brown et al. (1998). We surveyed our Old World haplogroup X mtDNAs for the five diagnostic X2a mutations (table 2) and found a match only for the transition at np 12397 in a single X2* sequence from Iran. In a parsimony tree, this Iranian mtDNA would share a common ancestor with the Native American clade (fig. 2). Yet, the nonsynonymous substitution at np 12397 converting threonine to alanine cannot be regarded a conservative marker, as it has also been observed in two different phylogenetic contexts--in haplogroups J1 and L3e--among 794 complete mtDNA sequences [citations omitted]. Therefore, the scenario that the threonine to alanine change in the haplogroup X background is indeed due to recurrence appears most plausible.
They also suggest that the haplotype X among the Altain people of Siberia is likely due to a relatively recent flow of genes from Eurasia, which may also have brought some of the other European haplotypes found among the Altains.
The possibility that haplotype X in Native Americans comes from recent admixture can be rules out on several grounds, especially the fact that haplotype X has been detected in pre-Columbian ancient DNA from the Americas (Malhi and Smith, 2002):
The most convincing evidence that haplogroup X is not the result of Viking or even more recent European admixture would be its presence in ancient Native Americans. Ancient samples from the Norris Farms site (Stone and Stoneking, 1998), the Windover site (Hauswirth et al., 1994), and the Amazon Basin (Ribeiro-Dos-Santos et al., 1996) exhibit the characteristic HVSI control region markers found in individuals assigned to haplogroup X, but they could not be confidently assigned that haplogroup because they were not tested for the AccI restriction site at np 14,465. We confirmed the presence of haplogroup X in one prehistoric sample excavated at a site on the Columbia River near Vantage, Washington and radiocarbon dated to 1,340 40 years BP.
Regardless of the origins of the major mtDNA haplotypes (A, B, C, D, and X), not all ancient Americans carried these haplotypes. Salzano (2002) reviews several studies of pre-Columbian mtDNA and notes that there have been samples found that cannot be classified within these groups. For samples from Florida (Windower), 69% could not be classified as A, B, C, or D. For samples from ancient Amazon Indians, 39% were outside the major haplotypes, and less than half of those could have been X (Riberos-dos-Santos, 1996 and 1997).
All in all, the expectations that studies in ancient DNA could provide new insights in the Amerindian evolutionary histories have not yet been fulfilled. It is not clear whether the new mtDNA sequences observed in prehistoric skeletons and mummies belong to lineages previously present but now extinct, or are methodological artifacts.
Given the existence of haplotype X (not directly related to Asian genes) and other mitochondrial haplotypes besides Asian A, B, C, and D in the ancient Americas, it is scientifically unsound to claim that DNA evidence points to Asia as the sole source of the ancient inhabitants of the Americas.
As an example of other haplotypes besides A, B, C, D, and X, and previously unknown haplotype has been found in the oldest ancient DNA sample from the Americas, see National Geographic's article, "First Americans Arrived Recently, Settled Pacific Coast, DNA Study Says," Feb. 2, 2007, which reports that DNA from a tooth sample over 10,000 years old does not belong to the five dominant haplotypes, and represents a previously unknown form that is related to a very small number of modern Native Americans along the Pacific Coast. This evidence may require significant revision of previously taught versions of the settling of the Americas.
A recent post at Mormanity discusses an outstanding essay on the FAIRBlog, "Current Biology, SMGF, and Lamanites" by Dr. Ugo Perego, a scientist with a Ph.D. in human genetics and Director of Operations and Study Research Coordinator at the Sorenson Molecular Genealogy Foundation, Dr. Perego shows proper discipline in not making unfounded conclusions and in warning that much more work remains to be done in understanding Book of Mormon issues. Here is one example, where a potentially exciting report from other respected scientists is put in proper perspective:
Much can still be said about haplogroup X2 in the Americas. In our paper, two sub-branches of the Native American haplogroup X2a have been classified as X2a1 with an estimated age of 9200-9400 years and as X2a2 with an estimated age of 2300-3800 years. A possible third X2a sub-branch (X2a3?) was identified among the indigenous groups of British Columbia in Canada, but there is not sufficient data at this time to confirm this hypothesis. Furthermore, we reported in this paper the discovery of a previously unidentified X2 lineage in an Ojibwa sample -- which we named X2g -- that has never been previously observed in Native American populations or elsewhere.
Lastly, a paper published on PLoS One in 2008 (Shlush et al.) provides important clues about the possible origin of haplogroup X: "No population or geographic region has been identified to date, in which haplogroup X and its major subhaplogroups are found at both high frequency and high diversity, which could provide a potential clue as to their geographic origin. Here we suggest that the Druze population of northern Israel may represent just such a population."
Our paper in Current Biology does not discuss (and does not dismiss) a potential ancient origin for haplogroup X in the ancient Near East, as proposed by Shlush and Reidla (and their co-authors, including important names in population genetics such as Michael Hammer, Doron Behar, Toomas Kivisild, Richard Villems, Antonio Torroni, Alessandro Achilli, etc.), but we emphasize how this haplogroup marked a separate migratory event that characterized the history of Native American populations. Apart from anyone who believes haplogroup X to be the ultimate proof marking the arrival of Lehi's group to the Americas (something that neither Woodward, nor myself advocate), the bottom line is that there is still much to research about the origin and dispersal of this and the other pre-Columbian lineages.(Emphasis added.)
So while there is data from respected scientists suggesting a relatively recent link between Israel and a DNA marker in the Americas, it is far too early to get overly excited. But it may be fair to say that those who say that DNA evidence utterly refutes the Book of Mormon are in an even less defensible position. Haplotype X may have some relevance to the debate, though that remains to be seen. It's still tentative, even speculative, but interesting.
In addition to providing a brief update about recent developments in relevant DNA studies, Dr. Ugo Perego's essay also shows some of the troubling tactics used by some anti-Mormons trying to use the DNA issue to attack the Church. It's very insightful and consistent with some of my experiences.
Let's assume for a moment that the Book of Mormon record is factual and that Lehi, Mulek, and their cohorts brought DNA from the Middle East into the New World around 600 B.C. Given that there were many people already in the hemisphere, then it is likely that modern traces of that Middle Eastern DNA will be found only rarely using techniques that require a pure, unbroken line of maternal or paternal descent from the tiny bands reported in the Book of Mormon. Those Native Americans with mtDNA directly inherited from Sariah, for example, or those with Y chromosomes directly inherited from Lehi, Mulek, Ishmael, or Zoram, may stand out as unusual outliers in genetic testing. In fact, it is possible that their DNA may resemble haplogroups typically found in Europe--especially if that is where the lost tribes of Israel ended up after the Assyrian conquest of the Northern Kingdom around 700 B.C. (Lehi was of the tribe of Joseph, not Judah, making him a fortunate remnant of one of the lost tribes of Israel. We may expect his DNA to resemble that of various peoples who may be found in Europe or Asia.)
Unfortunately, in their struggle to avoid samples contaminated with modern genetic matter and to avoid using Native American subjects who appear to have genes brought by Europeans after the time of Columbus, scientists may discard any evidence of relatively recent introduction of European haplogroups. And 600 B.C. is recent compared to the assumed time frame for settling of the Americas, which spans 12,000 to 40,000 years ago.
But whether the source is recent admixture or admixture from Lehi's group in 600 B.C., one point needs to be made that contradicts common claims of Book of Mormon critics: there IS direct evidence of Jewish ancestry among some modern Native Americans. Of course, this evidence will be assumed to be due to modern admixture--but can we really be sure of that?
One recent example is that of Carvajal-Carmona et al. (2000 - available online), who studied the Antioquian population of Colombia:
A number of the Antioquian Y-microsatellite haplotypes shown in table 4 carry large alleles at locus DYS388 (alleles with >14 repeats). These alleles are absent or have low frequencies in European and African populations but reach high frequencies in Middle Eastern populations (Kayser et al. 1997; Thomas et al. 2000). Large alleles were detected in the Basque and Catalan populations, at frequencies of 3.9% and 3.7%, respectively, and, in Antioquia, at a frequency of 16.2%. Among the Arabs, Berbers, Saharawis, and Tachelhits, such alleles were found at frequencies of 8.9%, 0%, 10%, and 11%, respectively. This suggests some Semitic ancestry for Antioquia and is consistent with the genetic distance analysis of table 3. Interestingly, haplotype 4, which carries a DYS388 allele with 16 repeats, corresponds to the Cohen modal haplotype (CMH) of Thomas et al. (1998). This haplotype has frequencies >10% among Jewish populations but seems to be rare in Arab populations and has been proposed as an indicator of Jewish ancestry (Thomas et al. 2000). Two other haplotypes (12 and 29) are one mutational step away from the CMH. Haplotypes 3 and 5 also match haplotypes detected among Jewish populations; they correspond to haplotypes 2 and 27 in Thomas et al. (2000). In that survey, Antioquian haplotype 3 was observed only among Sephardic Jews. These matches occur in haplogroup C and, on aggregate, imply that ~14% of the Antioquian haplotypes could have a Jewish ancestry.
This Jewish ancestry is assumed to be due to Jews living in the Iberian peninsula who came to the Americas with the Spaniards, but it is difficult to conclusively prove that given the lack of significant documentary evidence. But the blood types of the Antioquians points to heavy European influence (again apparently modern) and we know that Europeans are among their ancestors. But even if we grant that some of their genes came from modern Jews, do we have the tools to identify genes brought by a group like Lehi's in 600 B.C., if they have survived as mtDNA or Y-chromosomes? Would they not be classified as of modern origin or become part of a neglected "other" category? NOTE: I don't think the Antioquians have Y chromosomes from Lehi, but use them as an illustration of the reality of "Jewish" DNA in the Americas and the difficulty in properly identifying its source.
In studying the genetics of Native Americans, the problem with admixture is real, of course. European genes as well as African genes (Green et al., 2000) have been introduced since Columbus. But automatically discarding apparently "recent" genetic ties to Europe may be premature in some cases. To better understand this issue, below are several examples of how European-like genetic features are discarded because of fear of recent admixture. First, I quote from Forster et al. (1996), p. 936:
Three of these 574 sequences were discarded for the analyses because they represent obvious cases of admixture: one Chilean, already identified as an outlier by Horati et al. (1993), differs by only one unique mutation from a common European/Middle Eastern sequence, and a Haida, and a West Greenland Inuit (35 and 83 in Shields et al. 1993) are not found in any other American or Siberian sample but reveal two exact matches with two of the most-common European sequences.
Forster et al. (1996) also note that the criteria of Torroni et al. for identifying founding haplotypes could miss minor founding haplotypes (p. 938), a reminder that small groups of migrants are likely to be overlooked as scientists characterize the genetic origins of Native Americans, even when the unusual groups aren't thrown out.
Torroni et al. (1993b) discusses haplogroups that do not fit the 4 main haplogroups of Native American mtDNAs:
Haplotypes Am28, AM29, and AM74-76 lacked characteristic Amerind mutations and probably represent European mtDNAs. For example, haplotype Am28 was found in one Maya. . . . The same haplotype has been found in about 10% of Caucasian mtDNAs, and if haplotypes deriving from AM28 are included, the frequency of this group of haplotypes increases to about 30%.
Later, Torroni et al. (1995) take a less tentative stance in referring to their previous work: "The Maya haplotype (AM28) lacking Native American markers is of European origin." What was "probably" in their earlier paper is now stated in absolute terms, though no new evidences supports the bolder statement. They may be right, of course, but are they really sure?
Santos et al. (1999), already discussed above, provides another typical example. In the following quote, look how casually and quickly recent ties to Europe are discarded. It is understandable, but perhaps important evidence is conveniently overlooked:
The major Amerindian haplotype . . . is described here as haplotype 31. . . . Haplotype 10, differing from haplotype 31 only by [a single mutation], was very frequent (30%) in our Native American sample and was found exclusively among North American Indians; in addition, it was also observed in a Mongolian and four Indians. Haplotype 20, which is similar to haplotypes 10 and 31, was seen in a single North American Indians and in some populations from the central region of Siberia. It was particularly frequent in a sample of the rapidly disappearing Ket population (70%) and also was found in some Altaians (17.4%) and a single Mongolian. Haplotype 23, which is very different from haplotypes 31, 10, and 20, was seen in a single Na-Dene and could be a more recent haplotype from Asia, since it is most frequent in Mongolia (42%) and is also seen in many Siberians. . . . Haplotype 1, also similar to haplotype 10 and the most frequent in Europe (53%), is also present in India (14.5%) and was found in 20% of the Native Americans, exclusively in the samples collected for paternity tests in North America, but is absent from Siberia or central East Asia. European ancestry was confirmed for at least one of these  Native American samples with haplotype 1 in the paternity-test report. Therefore, the presence of haplotype 1 in North American Indians can be explained as a result of recent admixture with Europeans, whereas haplotypes 10, 20, and 23 cannot be explained in the same way, because they are absent from Europe.
One of four people with an unusual European haplotype could be shown to have some presumably modern European ancestry--how that was shown is not stated--and thus the authors dismiss all occurrences of this haplotype as being due to recent admixture. Was this ancestry strictly paternal, so that a Y-chromosome had been inherited from a European? Did the other 3 individuals with haplotype 1 also have paternal European ancestry? The authors may be right in their conclusion, but have other possibilities been considered carefully enough?
The risk of ignoring apparent outliers and the incomplete nature of the "Asia only" model for Native American origins is discussed by David A. McClellan (2003), assistant professor of integrative biology at Brigham Young University:
Another haplotype, C10, [Rickards et al., 1999] is found only among the Cayapa people of Ecuador, who possess it in relatively high frequencies (30 percent). C10 does not appear to be closely related to any other extant human haplotype, although it appears that it may be loosely related to haplogroup C to the exclusion of haplogroups B and A. At best, haplotype C10 represents a lineage that has a questionable origin.
Mitochondrial studies have also been performed with the remains of ancient Maya from the Postclassic period of a.d. 900-1521, just prior to European colonization. [González-Oliver, 2001] Findings include the identification of a single individual (1 out of 16) whose mitochondrial haplotype failed to correspond to any of the known extant haplogroups (A-D). Although another unidentified haplotype was isolated among contemporary Maya, it was discounted as the product of modern European admixture. [Torroni et al., 1992] However, the presence of a similarly unidentified haplotype in ancient Maya may call this conclusion into question.
Although the preponderance of mitochondrial genome data supports the hypothesis that the Americas were originally peopled by humans from eastern Asia, the exact location of the source population and the number of migration waves remains controversial, [Neel et al., 1994; Kolman et al., 1996; Bonatto and Salzano, 1997b] despite claims to the contrary. [Derenko, 2001] The presence of haplotypes X and C10 and the "unknown" Maya haplotypes (both ancient and modern), however, emphasize the fact that much that has been discovered is yet to be explained. A hypothesis for the diversity of Native American mitochondrial genome haplotypes that relies exclusively on an out-of-Asia origin falls short of a complete explanation.
There are further indications that the "Asia-only" model is incomplete, and that hints of non-Asian origins may be too easily ignored. For example, in the work of Karafet et al. (1999), several Y-chromosome haplogroups were studied. Interestingly, a minority of the Native Americans displayed haplogroup 4 (1 Cheyenne and 2 Zapotecs). This haplogroup was one of the two major haplogroups for Greeks and the most common one reported for Egyptians, but was absent from Asians, Eskimos, and other North Americans. The work of Hammer et al. (2000) shows that haplotype 4 is also one of the most common haplotypes among Jews. Several other haplotypes may link scattered Native American individuals with Africans or Europeans (including the Mediterranean), though the genes in question occur to a small degree in some Asian populations as well.
Speaking of haplotype 4 and 5, which are grouped as YAP+ haplotypes, the authors state the following:
Only two of four YAP+ haplotypes (i.e., 4 and 5) were present in our survey of Native Americans. Because these haplotypes are limited almost entirely to Africa and Europe, the presence of YAP+ haplotypes in the New World is most likely due to admixture between Native Americans and people of African and European descent. (p. 823)
How do we distinguish genes introduced from the Middle East since Columbus from those introduced after Columbus? The key may be to examine pre-Columbian human remains. Though extremely rare, such remains may ultimately answer the question. One study has been reported of such remains. It is that of Stone and Stoneking (1998), who investigated a burial site with many pre-Columbian skeletons dating to about 1300 A.D. Of 152 individuals, 102 could be assigned to one of the four primary haplogroups (A,B,C,D), and 6 "did not possess any of the characteristic markers and were designated as belonging to a group designated "other"." The remaining 44 samples did not yield enough DNA for analysis. The HV1 [hypervariable region I of the control region in the mtDNA] was sequenced in 52 individuals (34%) from the total sample.
The individuals included 12 with mtDNA classified as group A, 7 as group B, 25 as group C, 5 as group D, and 3 as "other." Twenty-five distinct lineages were found. Two of these lineages (2 and 25) were excluded from further analysis, as likely cases of contamination (despite multiple independent extractions of these samples). The sequence of lineage 25 (from burial 200) matched the sequence of the primary author (A.S.). The lineage 2 sequence was identical to one found in two Finnish individuals (Lahermo et al., 1996) and segregates with the reference sequence in phylogenic analyses (data not shown). Although this sequence does not match the author's sequence of that of the primary osteologist involved with the sample, this lineage may be the result of contamination from an unknown source. Additional investigation of the mtDNA sequences of individuals involved with the skeletal collection may reveal the possible source for this sequence. Lineage 25 was from the "other" group (as is the primary author), whereas extracts from the individual with lineage 2 did have the gain of the HaeIII site that characterizes haplogroup A in Native Americans; however, this mutation has also been found in Caucasians (Cann et al. 1987). (Stone and Stoneking, 1998, emphasis mine)
Fascinating! The authors describe great care in the extraction procedures used. They examined a string of 31 nucleotides, most of which are unchanged relative to a reference sample. Sample 24, rejected for having the same sequence as the author's, differs by only two mutations from the reference series and by only 1 mutation from line 11 that is grouped with haplogroup B. Line 25 differs by only one mutation from the line 11 as well and by only two mutations from the reference sequence. It's not impossible that either of these sequences labeled as "other" were genuine Native American sequences. But since one corresponds to two published Finnish nucleotide sequences, it assumed that contamination somehow occurred. But could it also be that there was some European blood that showed up in a rare DNA sequence?
Based on the information published in this article, and comparing it with that of Finnila (2001), I find that one of Finnila's Finnish individuals (#112) of haplogroup X differs from ten of Brown et al.'s (1998) haplogroup X Native Americans (NA 12-21) by only one or two mutations. Specifically, both the native Americans and the Finn have mutations relative to the Cambridge Reference Sequence in nucleotides at positions 73, 153, 195, 225, 263, 16183, 16189, 16223, and 16278. Brown does not appear to provide information about nucleotide 329, where the Finn has a mutation. The Finn has a mutation at position 226 that is found in none of Brown et al.'s Native American samples. Thus, based on the published information, there are nine shared mutations, one mutation in the Finn not found in the Native Americans, and one in the Finn for which I have no information. Differing by only one or two mutations when nine mutations are shared strikes me as interesting. To put this in perspective, there were three other Finns sharing haplogroup X with individual 112, and in spite of their common haplogroup, they still differed from individual 112 by either 4 or 5 mutations. Finns with other haplogroups differed from individual 112 by larger numbers of mutations, with some differing by more than 20 mutations.
Interestingly, I've encountered another example of a respected researcher encountering Finnish-like genes in Native Americans and ascribing that to presumably recent European admixture. Torroni and Wallace (1995) discuss the "other" haplogroups that don't fall within the primary mtDNA haplogroups A, B, C, and D, which have been found in over 3% of Native Americans. After dismissing the previously discussed unusual Mayan haplotype (Am28) as European, they make the following statements:
An analogous case of admixture with Europeans is represented by the "anomalous" Ojibwa and the Navajo mtDNAs (AM29 and AM74-76). All of these haplotypes are defined by both a DdeI site loss as nt [nucleotide] 1715 and the lack of a DdeI site at nt 10394. This association was not observed in any of 411 Siberians and 207 Asians, suggesting that this haplogroup is not of Asian ancestry. The European ancestry of the anomalous Ojibwa and Navajo mtDNAs was initially suggested by the presence of two similar haplotypes in 2 of 175 Caucasians from North America and recently has been confirmed by the finding of mtDNAs with the same characteristic mutations in the Finnish population (author's unpublished data). (Torroni et al., 1995, p. 1235, references deleted, emphasis mine)
As if that weren't puzzling enough, a study of diabetes in Mexican Americans again points to a possible Finnish connection (Horikawa et al., 2000), though European admixture is certainly present.
Are the repeated genetic connections with Finns just coincidence? Torroni et al. (1995) find a close tie between some Finns and some unusual mtDNAs in Native Americans, allegedly "confirming" that they are due to recent admixture with Europeans. Stone and Stoneking (1998) investigate a pre-Columbian burial site and, in spite of extremely cautious procedures, feel that contamination from an unknown source must have occurred in one of their samples because it shows a sequence identical to that reported in two Finnish individuals, even though this sequence did not match that of the two researchers most likely to have accidentally contributed genetic matter. A study of diabetes suggests an association between Mexican Americans and some Finns. Finally, my comparison of data in Finnila et al. (2001) and Brown et al. (1998) shows that the connections between one Finnish individual and several modern X haplotypes in Native Americans may be surprisingly close, even though recent admixture is not suspected.
The origins of the Finns, by the way, are rather obscure. Some have speculated about lost tribes of Israel, but a Central Asian origin may be more plausible. If there is a connection with Native Americans, it may be through the ancient Jaredites rather than Hebrews--or it could be through the Vikings long after Book of Mormon times. For now, we don't know enough to make any firm conclusions.
The unusual outliers we encounter remind us of the significant diversity in genetic markers. Statements based on averages and typical features of groups may obscure important details, such as the similarity between a Finn and several Native Americans. And if there were a link between modern Finns and pre-Columbian settlers in the New World--such as both sharing genes from the lost tribe of Joseph, to give a radical example--would such a link ever be found if evidence for it were immediately but erroneously discarded due to apparent modern admixture? I'm not saying the Finn's have anything to do with Native American populations--but they might.
The problem in applying DNA analysis to the Book of Mormon goes beyond the likelihood of discarding the most relevant evidence. There is also the possibility of attributing evidence of pre-Columbian migrations to recent admixture. Worse, there is the possibility of missing the date of entry of the most relevant genes, and thus eliminating them from the scope of the Book of Mormon, as we shall discuss below.
All this is compounded by the fact that researchers are understandably interested in explaining the dominant genetic origins of Native Americans, which will likely correspond to the dominant population groups that were already on the continent when Lehi's little boatload of people landed. There is typically little interest in understanding or even studying the origins of unusual haplotypes in Native Americans (e.g., Bonatto and Salzano, 1997a and Malhi et al. 2002).
An excellent discussion of the very real problem of contamination of ancient DNA samples is provided by Kolman and Tuross (2000), who also provide an interesting example in which pre-Columbian genetic material from a Native American appears to provide reproducible evidence of European origins. In spite of numerous efforts to exclude contamination, this result, identically reproduced in multiple careful trials, is presented as a case of "obvious" contamination because it was non-Asian:
The data presented here can be used to illustrate the dangers of imprudent inclusion of data. The DNA sequence identified in sample 5 had never been detected in our laboratory or in New World indigenous populations. All associated extraction and PCR controls were negative. Multiple extractions resulted in the same RFLP/deletion haplotype. Therefore, it could be proposed that this haplotype represents a new founding lineage for the New World. However, the fact that this haplotype is found at high frequency in European populations (17%, Richards et al., 1996) and is not found in presumably ancestral Asian populations argues against this interpretation and against the inclusion of this sequence in a NewWorld database.
In total, seven different non-New World sequences were identified in the current study. They are most likely all European in origin and may represent a minimum of seven independent sources of contamination. . . .
In sum, there is no easy, objective method of identifying contaminating sequences other than to painstakingly analyze them within the genetic framework of the ancient population under study.
The conclusion is understandable, if one is constrained by the paradigm that all ancient Native Americans must have DNA originating from Asia. But when an ancient human's DNA comes up as European, in trial after trial with great precautions taken to prevent contamination, and then that data is simply excluded as a fine example of the dangers of contamination because it is not Asian, what chance do we have to find non-Asian genes in ancient human samples from the Americas? Ancient DNA that does not fit the out-of-Asia paradigm is repeatedly discarded from consideration because of "obvious" contamination.
There is no evidence in the paper by Kolman and Tuross that any of the other samples discarded for "contamination" had contamination from any of the researchers conducting the study. The approach appears to be that anything unexpected will be discarded as due to contamination. Is it any surprise that this approach - apparently a common approach - consistently suppresses surprises, surprises like the presence of non-Asian groups in ancient America?
Further work with the typically neglected outliers still needs to be done, and done without instantly assuming that modern contamination or admixture is the source of genes that appear to have a non-Asian origin. While contamination can be a serious problem, it is still possible to get good results with ancient DNA if proper procedures are followed, as shown by Gilbert et al. (2003). More recently, Matthew Spencer and Christopher J. Howe (Spencer and Rowe, 2004) have established statistical tools and recommended procedures to help researchers determine the probability that an amplified DNA sequence from an ancient sample actually corresponds to ancient DNA or modern contamination. Their discussion of the problem of contamination is also helpful.
Guthrie (2000/2001) notes examples in which genetic data were excluded due to incorrectly assumed admixture. Admixture is a problem, but there is also a real risk of errantly disregarding genetic data by assuming recent admixture, when in fact a gene with ties to the Old World may have arrived well before Columbus. And part of the difficulty is the uncertainty in assigning a date to the entry of a gene.
Much of the analysis assumes that diversity within a haplogroup is due to mutations occurring at slow, predictable rates that occurred since migration to the New World. However, Malhi et al. (2002) note that, "If multiple haplotypes within a haplogroup were successful colonizers of the New World, modern values of within-haplogroup diversity would overestimate the accumulated variation since contact." They further note that in the HVSI portion of the control region of mtDNA used to make estimates of dates, the entire region itself may be hypervariable, resulting "in a nonlinear accumulation of mutations within a haplogroup, thereby further impairing the utility of molecular diversity for the dating of the colonization event. Diversity estimates are also strongly affected by both sampling and population historic and demographic events that have occurred since colonization."
Further, comparison of haplogroups does not reveal travel routes. Finding DNA in a small group in southwest Siberia that resembles DNA from many Native Americans DOES NOT indicate who traveled where and when. Even if we know that the two groups have been separated by 12,000, years, for example, it is possible that the small Siberian group descended from ancient New World peoples who migrated to Siberia.
To illustrate the impossibility of precisely dating events with DNA analysis alone, consider this statement from Karafet et al. (1999):
Haplotypes constructed from Y-chromosome markers were used to trace the origins of Native Americans. Our sample consisted of 2,198 males from 60 global populations, including 19 Native American and 15 indigenous North Asian groups. . . . Contra previous findings based on Y- chromosome data, our new results suggest the possibility of more than one Native American paternal founder haplotype. We postulate that, of the nine unique haplotypes found in Native Americans, haplotypes 1C and 1F are the best candidates for major New World founder haplotypes, whereas haplotypes 1B, 1I, and 1U may either be founder haplotypes and/or have arrived in the New World via recent admixture. Two of the other four haplotypes (YAP+ haplotypes 4 and 5) are probably present because of post-Columbian admixture, whereas haplotype 1G may have originated in the New World, and the Old World source of the final New World haplotype (1D) remains unresolved. The contrasting distribution patterns of the two major candidate founder haplotypes in Asia and the New World, as well as the results of a nested cladistic analysis, suggest the possibility of more than one paternal migration from the general region of Lake Baikal to the Americas.
Those findings illustrate an important point. Using state-of-the-art techniques, Karafet et al. (1999) were unable to state whether haplogroups ("haplotypes" in their paper) 1B, 1I, and 1U were founder haplogroups (entered the New World many thousands of years ago) or have arrived in the New World via recent admixture. YAP+ haplogroups 4 and 5, with strong ties to European genes, are said to be "probably present because of post-Columbian admixture"--but that is an assumption, not the result of any precise dating methodology. Interestingly, of the Old World population groups studied by Karafet et al., those with the highest concentration of YAP+ haplogroups were in the Mediterranean. Could it be that the YAP+ haplogroups in the New World were due to admixture, but pre-Columbian admixture from Middle Easterners? That possibility cannot be ruled out.
Karafet et al. also found that haplogroup 1C "was also widely distributed in North, Central, and South America. In the Old World, the highest frequencies of haplotype 1C were found in the Kets (83.3%) and the Selkups (76.2%)" (p. 821). However, the second highest Old World frequency for haplogroup 1C was in Britain, with 68.8% frequency. The European group as a whole had this haplogroup at only a 37.7% frequency. Could there be a tie to Britain?Adachi and Hasegawa, 1995), I began to wonder just how much verifiable science went into the estimated dates of separation of various human lines. Could human lines be mutating much faster than had been assumed or estimated? If there are major errors in the mutation rates that are used to date genetic separation of human groups, then our application of the DNA evidence to New World origins could be wildly misleading. In fact, there is reason to doubt the standard mutation rates used.
I first encountered this evidence on a Web page by David A. Plaisted, "Mitochondrial DNA Mutation Rates," which refers to the work of Parsons et al. (1997), who provide the following summary:
The rate and pattern of sequence substitutions in the mitochondrial DNA (mtDNA) control region (CR) is of central importance to studies of human evolution and to forensic identity testing. Here, we report a direct measurement of the intergenerational substitution rate in the human CR. We compared DNA sequences of two CR hypervariable segments from close maternal relatives, from 134 independent mtDNA lineages spanning 327 generational events. Ten substitutions were observed, resulting in an empirical rate of 1/33 generations, or 2.5/site/Myr. This is roughly twenty-fold higher than estimates derived from phylogenetic analyses. This disparity cannot be accounted for simply by substitutions at mutational hot spots, suggesting additional factors that produce the discrepancy between very near-term and long-term apparent rates of sequence divergence. The data also indicate that extremely rapid segregation of CR sequence variants between generations is common in humans, with a very small mtDNA bottleneck. These results have implications for forensic applications and studies of human evolution.
Further, the authors (Parsons et al., 1997) state:
The observed substitution rate reported here is very high compared to rates inferred from evolutionary studies. A wide range of CR substitution rates have been derived from phylogenetic studies, spanning roughly 0.025-0.26/site/Myr, including confidence intervals. A study yielding one of the faster estimates gave the substitution rate of the CR hypervariable regions as 0.118 +- 0.031/site/Myr. Assuming a generation time of 20 years, this corresponds to ~1/600 generations and an age for the mtDNA MRCA of 133,000 y.a. Thus, our observation of the substitution rate, 2.5/site/Myr, is roughly 20-fold higher than would be predicted from phylogenetic analyses. Using our empirical rate to calibrate the mtDNA molecular clock would result in an age of the mtDNA MRCA of only ~6,500 y.a., clearly incompatible with the known age of modern humans. Even acknowledging that the MRCA of mtDNA may be younger than the MRCA of modern humans, it remains implausible to explain the known geographic distribution of mtDNA sequence variation by human migration that occurred only in the last ~6,500 years.
While our results are at odds with those of phylogenetic studies, they are in excellent agreement with a recent report that also directly measured the CR substitution rate." (op. cit. p. 365; footnotes omitted; the report mentioned in the last paragraph is Howell, N. et al., in Am. J. Hum. Genet. 59, 501-509, 1996).
Plaisted notes that the control region is an unimportant part of human DNA, as far as we know (part of the "junk DNA" that does not code for proteins), so the observed high rate of mutation is not likely to be reduced by an order of magnitude in effect by sudden death caused by 90% or so of the mutations being harmful. The mutations in the unimportant control region DNA are likely to persist from generation to generation. The bottom line is that human mutation in that region occurs much faster than we have previously assumed. See also Gibbons (1998), who states:
Mitochondrial DNA appears to mutate much faster than expected, prompting new DNA forensics procedures and raising troubling questions about the dating of evolutionary events.
Some people are using the work of Parsons et al. to reduce the estimated age of "mitochondrial Eve" from 200,000 years ago to, oh, about 6500 years ago. See, for example, the Web page at http://www.mhrc.net/mitochondria.htm. I remain skeptical of this approach and am much more comfortable with the analysis of, say, Rana et al. (1999), where I feel the reality of fossil evidence is better understood.
Nevertheless, based on what Parsons et al. have demonstrated, dates of genetic entry in the New World based on genetic evidence may be off by an order of magnitude. If this holds up, then haplogroup X and other European haplogroups X in the Americas really may point to a Middle Eastern entry from about the time of Lehi, rather than 12,000 to 30,000 years ago. Time will tell.
Recently, Sean D. Pitman, M.D., published an article (Pitman, 2003) exploring the scientific problems behind using DNA analysis as a clock to date human origins. He summarizes a variety of scientific findings pertaining to mutation rates and the methods used to date DNA. I highly recommend his article as a resource on this topic. It is available at http://naturalselection.0catch.com/Files/dnamutationrates.html.
The above-mentioned work of Howell et al. (1996) merits further mention. Here is the abstract:
The results of an empirical nucleotide-sequencing approach indicate that the evolution of the human mitochondrial noncoding D-loop is both more rapid and more complex than is revealed by standard phylogenetic approaches. The nucleotide sequence of the D-loop region of the mitochondrial genome was determined for 45 members of a large matrilineal Leber hereditary optic neuropathy pedigree. Two germ-line mutations have arisen in members of one branch of the family, thereby leading to triplasmic descendants with three mitochondrial genotypes. Segregation toward the homoplasmic state can occur within a single generation in some of these descendants, a result that suggests rapid fixation of mitochondrial mutations as a result of developmental bottlenecking. However, slow segregation was observed in other offspring, and therefore no single or simple pattern of segregation can be generalized from the available data. Evidence for rare mtDNA recombination within the D-loop was obtained for one family member. In addition to these germ-line mutations, a somatic mutation was found in the D-loop of one family member. When this genealogical approach was applied to the nucleotide sequences of mitochondrial coding regions, the results again indicated a very rapid rate of evolution.
\ In my opinion, Howell et al. (1996) show that common assumptions about mtDNA mutation do not hold up. Not only can the rate of change be faster than expected, but recombination of mtDNA can occur (meaning that some mtDNA from the father is inherited). Though rare (see Elson et al., 2001), such a possibility could jeopardize the accuracy of conclusions drawn from mtDNA work.
The issue of unusually frequent mutations in mtDNA also arose in a study of Russian Tsar Nicholas II and family members, conducted by Ivanov et al. (1996) and discussed by Gibbons (1998). Both the tsar and his brother inherited two mtDNA sequences from their mother, a mutation-induced condition called heteroplasmy. Heteroplasmy was assumed to be a rare and unusual event, but "new studies suggest that [it] may in fact be a frequent event," found in at least 10% of humans, according to the summary of Gibbons (1998). Such frequent mutations may invalidate the assumptions behind previous DNA-based dating, according to Gibbons.
More recently, Denver et al. (2000) conducted a study of mtDNA mutations in one of biologists' favorite creatures, Caenorhabditis elegans, a nematode which, in spite of its simplicity, shares many essential biological features of relevance to human biology. Using a long-term study of mutations in these creatures, they found that the mtDNA mutation rate was roughly 100 times greater than previously used rates based on indirect estimates. The authors state:
The mutational patterns observed in the MA lines of C. elegans are similar to those associated with human mitochondrial diseases, including the replacement of highly conserved amino acids, large deletions, and the high incidence of frameshift mutations at coding homopolymer stretches. The mitochondrial mutations isolated in this study can serve as models for future studies on the fitness effects of mitochondrial genetic disorders. Furthermore, the high rate and strongly biased pattern of mtDNA mutations detected here increase the probability of parallel mutations. The high potential for homoplasmy must be considered when using mtDNA for evolutionary studies and when investigating the occurrence of recombination in mitochondrial genomes. (pp. 2343-2344)Multiple recent studies point to the possibility that human mutation rates in mtDNA are much greater than previously supposed. Such studies, typically based on direct measurement of mutation rates, may be more accurate for dating the divergence of human haplogroups than anything based on the assumption of steady evolution from a common ancestor with other primates--even if basic evolutionary assumptions are true.
The uncertainty in dating has been further compounded, in my opinion, by mtDNA analysis of Cheddar Man (see Kahn and Gibbons, 1997). Rana et al. (1999) make this observation about the analysis:
To add even more weight to the finding [that Neanderthals are not part of human evolutionary lineage], scientists have also analyzed mtDNA from an ancient modern human skeleton. A British team analyzed a portion of mtDNA in a 10,000 year old human skeleton found near Cheddar, England. The mtDNA from this skeleton differed from that of modern Europeans by only one nucleotide base pair--essentially identical to that of modern humans. The lack of "evolution" for humans over the last 10,000 years stands in sharp contrast to the differences seen between modern humans and Neanderthals.
So while mtDNA rates observed in modern humans is higher than expected, analysis of mtDNA in an ancient human has shown almost no sign of evolutionary change (mutations) over a 10,000 year period. At the moment, it seems fair to question that dating of human origins or human migrations based on DNA analysis alone. For example, Nei and Glazko (2002) state that "mtDNA evolves so erratically that the estimates obtained using mtDNA appear unreliable" and they therefore turn to analysis of nuclear proteins instead, though this also requires calibration points based on the assumption that distinct species evolved from common ancestors with a known divergence date. Though they refer to their own unpublished data to support the claim that mtDNA dating is unreliable, they also cite Gissi et al. (2000), who found that mtDNA mutation rates appear to vary unpredictably between orders and even closely related species. However, Gissi et al. also conclude that the variation between mammals was low, with a variability of no more than a factor of 1.8 between rates.
To be fair, some previously published concerns about dating due to recombination in mtDNA were due to errant work of one scientist, Erika Hagelberg, who published a paper indicating that rapid mtDNA changes in some Pacific Islanders must have been due to recombination (see Strauss, 1999, for a discussion of implications). Bryan Sykes, in his popular book, The Seven Daughters of Eve (2001, pp. 155-168), delves into the tense conflict between Hagelberg and him, in which Hagelberg finally retracted her conclusions since the apparent mutations were due to a technical error on her part. Sykes argues that the many previously expressed concerns over dating with mtDNA (see, for example, Strauss, 1999) were ill-founded, and that mtDNA dating has proven reliable after all. On the other hand, there are other issues that Sykes does not address, such as the observation with electron microscopy that male mitochondria can enter an egg and possibly recombine with mtDNA from the mother (see Strauss, 1999).
It is not just non-coding mtDNA where unexpectedly high mutation rates have been encountered. Adam Eyre-Walker and Peter D. Keightley's article, "High Genomic Deleterious Mutation Rates in Hominids," published in the prestigious journal, Nature (Eyre-Walker and Keightley, 1999) shows that mutations in the coding DNA of the nucleus occur at a much higher rate than previously realized, so high that it poses serious problems for standard evolutionary models. The reported conservative estimate is 4.2 mutations per person per generation, with 38% being deleterious--though the actual number might be significantly higher. While I do not think that this study calls Y-chromosome analysis directly into question, it seems to require that human genes are not as old as previously assumed. I recommend the report of Rana et al. (1999) for further information on human origins and DNA analysis. Regarding the work of Eyre-Walker and Keightley, Rana et al. state:
The authors had to rely upon a rare association of mutations, termed synergistic epistasis to explain why the numerous hypothesized deleterious mutations have not overwhelmed our genome. Instead of postulating the obvious (that the human genome is not as old as evolution would teach), evolutionists must rely upon the improbable to retain the evolutionary paradigm.
Eyre-Walker's and Keightley's finding regarding deleterious mutations in human genes was strengthened by the work of Nachman and Crowell (2000). They estimated a mutation rate for humans based on the genetic differences between chimpanzees and humans and based on an assumed initial population size of 10,000, an assumed divergence time of 5 million years, and a generation time of 20 years. If evolution produced chimps and man from a common ancestor according to these assumptions, calculated apparent mutation rates may range from 2 x 10-7 per nucleotide per generation for transitions at certain sites (CpG sites) to 2 x 10-9 for other types of mutations (length mutations), with an estimate of average mutation rate being estimated at about 2.5 x 10-8 per nucleotide per generation. The total mutation rate for humans would be about 175 new mutations in human DNA per generation (the calculated range would be from 91 to 238). The roughly estimated deleterious mutation rate U is about 3, meaning that there typically may be 3 harmful mutations per generation in humans, obtained by using a probably low estimate of 1.7% of the genome being functional ("subject to constraint"), giving the deleterious mutation rate of 175 x 0.017 = about 3. This value is nearly twice as high as the U value of 1.6 obtained by Eyre-Walker and Keightley (1999). In light of their calculations, Nachman and Crowell (2000) point out a problem for evolutionary theory:
The high deleterious mutation rate in humans presents a paradox. If mutations interact multiplicatively, the genetic load associated with such a high U would be intolerable in species with a low rate of reproduction [references omitted]. The reduction in fitness (i.e., the genetic load) due to deleterious mutations with multiplicative effects is given by 1 - e-U. For U = 3, the average fitness is reduced to 0.05, or put differently, each female would need to produce 40 offspring for 2 to survive and maintain the population at current size.
As a possible solution for the problem, Nachman and Crowell also appeal to the hypothesized mechanism of synergistic epistasis, wherein each additional mutation leads to a larger decrease in relative fitness, allowing accumulated mutations to be removed more readily by natural selection. However, little is known about this speculative mechanism and it may be an example of wishful thinking. It is reasonable to question the framework of evolutionary biology if the expected mutation rate is likely to lead to destructive levels of harmful mutations that accumulated in a species. The purely evolutionary paradigm is not fully consistent with the data.
What do we know about the mutation rate in Y chromosomes? In spite of a high mutation rate in coding DNA overall, the mutation rate of Y chromosomes is generally assumed to be known and to be small. For example, a rate of 1.5 x 10-4 for tetranucleotide loci was reported by Jin et al. (1994). In a study of Native American Y chromosomes, Underhill et al. (1996) concluded that the appearance of a mutation shared by many Native Americans and not shared outside of the Americas probably occurred about 30,000 years ago, providing a date for an ancestral population in agreement with mtDNA studies. However, they noted that Weber and Wong (1993) obtained a higher mutation rate of 2.1 x 10-3 which, if used in their study, would date the mutation to 2147 years ago, "which obviously represents an underestimate." The authors state that, "Knowledge of the mutation rate of this particular tetranucleotide would be important for validating this dating." We must realize that estimates of dates ascribed to Native American DNA types may be wildly incorrect, and that calculations leading to estimates in a Book of Mormon time frame will not be given a chance because that would "obviously represent an underestimate."
While further work needs to be done, it may be that the mutation rate for Y chromosomes is and always has been low, allowing for accurate dating of divergence in paternal lines. Such methods point to very ancient entry of founders in the Americas. (Indeed, Sykes states that Y-chromosome dating methods have generally validated mtDNA dating methods (Sykes, 2001, pp. 193-194)--but both sets of dating methods are based on evolutionary assumptions that naturally favor very old dates, in my opinion.) For example, Bianchi et al. (1998) directly estimated the mutation rate in Y-chromosomes by looking at 1,743 sets of DNA from father-son pairs and combined that with other data in the literature to yield a mutation rate of .0012. They applied this rate to estimate the age of a founding haplogroup in Native American DNA they call OA, a haplogroup shared by 5.7% of Native Americans, a haplogroup involving several mutations, including a mutation of C to T in the DYS199 allele which is found in many Native Americans but not in other populations. Using the estimated mutation rate and the existence of other Native American haplotypes that appear to be derived by mutations from a founding OA haplotype, the estimated time that the OA haplogroup has been in the New World--the time required for mutations to produce the divergent haplotypes--is about 22,770 years (minimum 13,500 years, maximum 58,700 years).
Bianchi et al. provide date estimates that appear to nicely fit standard Bering Strait theories. However, it is fair to question the accuracy of the mutation rate they obtain. There were zero relevant mutations in the father-son pairs they examined (something encountered in a different study by Dorit et al., 1995, and discussed by Pääbo et al., 1995). To obtain a mutation rate that they were comfortable with, they turned to other sets of data:
Thus, the rate of mutation [from the father-son pairs analyzed by Bianchi et al.] was 0, with a 95% upper confidence-interval limit of .0025. Two other direct estimations of mutation rates for Y-specific microsatellites have been reported in the literature. Heyer et al. (1997) found three mutations in nine Y-specific microsatellite loci (which include the seven loci analyzed in the present report) and in 213 independent meiotic events; this combination of loci and meioses represents a total of 1,917 generations. In addition, Kayser et al. (1997) found two DYS19 slippage mutation events in 626 father-son pairs. If we pool the data from the present report with the data from the reports by Heyer et al. (1997) and Kayser et al. (1997), the average mutation rate is .0012, with 95% Poisson confidence-interval limits of .00046 - .0028.
The estimated mutation rate is based on 5 apparent mutations grouped from several studies. I doubt if the sample size is large enough to provide real accuracy. One can also question whether the mutation rates in modern Caucasians (all of the father-son pairs Bianchi et al. observed were Caucasian) really applies to ancient New World populations. The small handful of mutations that Bianchi et al. study would have required 22,700 years if they occurred at a low, steady, random rate. On the other hand, it is possible that the mutations occurred in a few closely spaced steps. There is a possibility that environmental factors (UV exposure, pollutants, diet, exposure to radioactive minerals, etc.) may have been responsible for high bursts of mutations for some groups in ancient times, leading to mutations at much higher rates than we see today. (Perhaps all the mutagens from ancient flame-broiled mastodon resulted in mutation rates hundreds of times higher than see in modern humans.) While the dating methods for Y-chromosomes and mtDNA may have been done fairly and reasonably, the assumptions built into them are open to question.
Ruiz-Linares et al. (1999) studied Y-chromosomes in Colombia with improved methods and found evidence that appears to challenge the conclusions of those who claim that Amerind genes show evidence of only a single migration to the New World well over 20,000 years ago. According to their abstract:
Recently, Y chromosome markers have begun to be used to study Native American origins. Available data have been interpreted as indicating that the colonizers of the New World carried a single founder haplotype. However, these early studies have been based on a few, mostly complex polymorphisms of insufficient resolution to determine whether observed diversity stems from admixture or diversity among the colonizers. Because the interpretation of Y chromosomal variation in the New World depends on founding diversity, it is important to develop marker systems with finer resolution.
Their more refined methods pointed to two founding migrations at later dates than previously supposed, estimated to be between 5,675 and 18,462 years for one group, and 9,334 and 11,456 years ago for another group. Recognizing that these dates are much less than the dates obtained from mtDNA, they simply hint that their numbers may be biased downward by their exclusive use of Colombian samples, but offer little reason to support this hopeful suggestion. (If Y-chromosome evidence can sustain a migration on the order of 5,000 years ago, we may be able to consider evidence of the Jaredites in the Americas--a people that Hugh Nibley has suggested were of Asiatic origin many decades before DNA evidence was available.)
On a more global scale, the recent Y chromosome work of Thomson et al. (2000) may require a further revision to previously proposed dates for the most recent common male ancestor of humans. Prior work had proposed dates greater than 100,000 years (sometimes greater than 500,000 years), but improved methods applied by Thomson put the date closer to 50,000 years. But even this is based on an assumed evolutionary split between humans and chimpanzees at 5 million years ago. If chimps and humans were created using different pathways (but common building blocks), then the assumption is incorrect and the dates obtained are meaningless. As the date for a common ancestor for all humans gets moved forward, the date for entry of founding chromosomes into the Americas could be expected to follow. (2014 update: evidence for common ancestry and not just common building blocks comes from the study of ERVs. Complex topic, but a useful and popular article is "Three Layers of Endogenous Retroviral Evidence for the Evolutionary Model". For another perspective, also see "Do Shared ERVs Support Common Ancestry?" which argues that these common elements in human and primate genomes may be due to chance after all and do not necessarily require common ancestry. But some of the supporting evidence may not be accurate, as explained in the response from EvolutionaryModel.com. Interesting!)
Clearly, we must wait for further refinements, even if we tentatively accept the conclusions of these studies at the moment.
Finally, mtDNA mutation may not be the result of neutral mutations, as is often assumed, but may be subject to the influence of natural selection, possibly challenging the accuracy of dating techniques. One interesting discussion of this point is offered by John Woodmorappe in his essay, "Upsetting Pet Theories: Surprising New Evidence that Molecular Clocks Can Run Very Fast," which discusses two scientific publications that point to the reality of natural selection in mtDNA and the possibility that this may result in inflated mtDNA dates.http://www.talkorigins.org/faqs/homs/mtDNA.html. An excerpt follows:
The use of mitochondrial mtDNA to investigate human history is not without drawbacks.
The rate of mtDNA mutation is not well known. A study by Parsons et al. (1997) found a rate 20 times higher than that calculated from other sources. In an article reviewing mtDNA research, Strauss (1999a) reports that mtDNA mutation rates differ in some groups of animals, and can even vary dramatically in single lineages. Although there are many agreements, some divergence dates for modern animals calculated from mtDNA do not match with what is known from the fossil record. There are suggestions from a few sources that paternal mtDNA can sometimes be inherited, which could affect analyses based on mtDNA.
In 1999 Awadalla et al. published a study suggesting that mtDNA could sometimes be inherited from fathers. If mtDNA is inherited only from mothers, the correlation between different mutations should not depend on how far apart on the genome they were. Instead, their measurements showed that mutations at distant sites on the mtDNA genome were less likely to be correlated than nearby mutations, suggesting that mtDNA from mothers and fathers could sometimes get mixed. However, there is no explanation so far as to how this recombination could be occurring, and the possibility that other phenomena could be causing this effect has not yet been disproved. If it occurs, mixing would mean that the dates from current mtDNA studies would be too old. If mixing is common enough, it could even mean that there was no mitochondrial Eve, because different parts of the mtDNA molecule would have different histories. (Awadalla et al. 1999, Strauss 1999b) Other studies, however, have contradicted these results and argued for strictly maternal mtDNA inheritance (Elson et al., 2001).
The possibility of paternally inherited mtDNA was fortified with a recent report in the prestigious New England Journal of Medicine by Marianne Schwartz and John Vissing entitled "Paternal Inheritance of Mitochondrial DNA" (Schwartz and Vissing, 2002). They report a case study in which a 28-year-old man was found to have a mutation in his mtDNA that was paternal in origin and was found in about 90% of the patient's muscle DNA. This is surely a rare event, but it does point to the possibility of unusual events in mtDNA transmission.
With both mtDNA and Y-chromosome analysis, we need to remember that there are multiple scenarios that can explain the observed results. Barbujani and Bertorelle (1998) explain:
One difficulty with modern genes lies in the fact that any given pattern of variation may potentially be explained by several different evolutionary phenomena. A cline or gradient, for example, may reflect adaptation to variable environments, or a population expansion at one moment in time, or continuous gene flow between groups that initially differed in allele frequencies. However, it is possible to discard at least some implausible models by jointly analyzing many loci (selection tends to affect single genes, whereas demographic changes determine similar patterns across the genome), and by exploiting nongenetic information, such as archeological and paleobiological data.
Thus, DNA evidence on its own must be approached with a recognition that several alternate scenarios could give rise to the observed results. Caution is always needed in interpreting the data.
Scientists have increasingly warned of the need for caution now that DNA evidence has posed tough new questions for previous evolutionary assumptions. For example, mtDNA analysis of Neandertals suggests that we are not descended from them, contrary to previous assumptions (see the BBC news item of March 29, 2000, "Neanderthals Not Human Ancestors"; see also Krings et al., 1997; Gee, 2000; Ovchinnikov et al., 2000). But, some scientists warn, mtDNA analysis may not reflect the actual relationship between us and Neanderthals. Though I have no trouble discarding the Neanderthals as our ancestors, I agree that great caution must be used in drawing conclusions based on DNA analysis alone. Here, for example, is a cautionary statement from Adcock et al. (2001):
Different regions of the genome appear to have different evolutionary histories, and the idea that the pattern of human evolution can be deduced solely from the pattern of contemporary mitochondrial genome diversity is becoming increasingly untenable....
[mtDNA] results have been widely argued as evidence that Neandertals did not contribute genes to contemporary Europeans, thus supporting the recent out of Africa model. This interpretation may not be justified. mtDNA is a small component of the total genome, and the failure of a mitochondrial lineage to survive to the present does not imply a similar failure for the remainder of the genome. (emphasis mine)
In addition, there has been much recent publicity about errors in mtDNA databases, though these errors seem unlikely to change broad conclusions being drawn about the Americas. Carina Dennis reports news about these errors in the news story, "Error Reports Threaten to Unravel Databases of Mitochondrial DNA," Nature, Vol. 421, Feb. 20, 2003, pp. 773-774:
More than half of all published studies of human mitochondrial DNA (mtDNA) sequences contain mistakes, according to a geneticist at the University of Cambridge.
To the occasional chagrin of his peers, Peter Forster has repeatedly pointed out errors in published mtDNA sequences. . . . But his commentary in the latest issue of Annals of Human Genetics argues that the problem is far bigger than researchers had imagined.
The mistakes may be so extensive that geneticists could be drawing incorrect conclusions in the studies of human populations and evolution, says Forster.
However, some scientists question the impact of these errors, and suspect that only a small number of studies are seriously jeopardized by them.
I am finding that some of our critics get riled when I suggest that DNA studies have limitations that must be considered. I suppose that they are used to thinking that everything they see in their anti-Mormon videos is clearcut and known, as if genetic science had the same fundamentalist flavor that some critics seem to favor.
Recent work with mtDNA in Iceland sheds even further light on how mtDNA lines can vanish. Here is an excerpt from Ugo Perego's excellent article, "The Book of Mormon and the Origin of Native Americans from a Maternally Inherited DNA Standpoint" (Perego, 2010):
Using the mtDNA mutations as a guide, it is possible to trace all modern mtDNA lineages back to a single African female ancestor. Geneticists have named this ancestor the African "Eve," but despite this name, she was not necessarily the only woman on the planet. The mtDNA lineages corresponding to other women simply disappeared because their offspring failed to produce additional continuous female lineages (a phenomenon known in population genetics as genetic drift), because of natural or manmade calamities that wiped out a significant portion of the population (an event referred to as a population bottleneck), or because they were selected against due to the detrimental effect of specific mutations. This African "Eve" was the only one that was successful in perpetuating her mtDNA lineage through the generations. Therefore, because of genetic drift, population bottlenecks, or natural selection, the mtDNA lineages observed in today's population do not reflect the full range of mtDNA variation that occurred throughout human history. A recent example from a study in Iceland based on genetic and genealogical data clearly demonstrated how the majority of people living in that country today are just a small representation of people that lived just three hundred years ago. [Helgason et al., 2003] This work is a powerful illustration and a rare example of a controlled study where genealogical, historical, and genetic data are available to unequivocally demonstrate the effect of genetic drift and natural selection in a fairly isolated population. The effect of these population genetics processes occur globally (including in organisms other than humans) and are not exclusive to the Icelandic population. Most relevant to our current discussion, these principles have also affected populations in the Western Hemisphere. Although some would like to dismiss the Icelandic model and suggest that it is more an exception than the rule [Southerton], these population genetics laws cannot be ignored: they are the fundamental force that shaped the modern genetic landscape worldwide. It is a well-known fact that mtDNA lineages have disappeared in the past and that they will continue to disappear in modern times. This process has occurred everywhere in the world, and the Americas are no exception.
Suppose a couple boatloads of Hebrews from 600 B.C. landed in the Americas (Lehi's group and the people that came with Mulek at about the same time). Even if they represented a minute fraction of the human genetic matter on the continent, shouldn't we still see traces of Hebrew genes in Native Americans today?
There are simple but unlikely scenarios that could allow for Hebrew genes to be all over the continent, but not in the form of readily detectable mtDNA or Y chromosomes. For example, suppose none of Lehi's group had any daughters that survived in the New World, resulting in the next generation of men taking local women as wives. In one generation, all Hebrew mtDNA would have been lost, even though Lehi's descendants remained on the continent, still rich in Hebrew DNA. Such an effect could be achieved in several steps, rather than all at once, including the effects of war, disease, and so forth. (On this issue, see the statistical analysis of Stacey et al., 2008.) The same could happen to the Y-chromosomes. But it's much more likely that some purely paternal or purely maternal lines remained intact, at least for many centuries. And they may be present today. But if the Hebraic immigrants to the Americas represented far less than 0.1% of the population of the New World, as they surely did, one would expect to find far less than 0.1% of modern Native Americans having Y chromosomes or mtDNA from Lehi's group. Now there may be some groups where Lehi's genes are more concentrated, and they may or may or may not have been measured yet. If they have been measured, would we know what to look for, not knowing the makeup of Lehi's or Sariah's genes? And if a single unusual outlier were found with remarkable resemblances to, say, modern Europeans, wouldn't it be rejected as a case of either obvious admixture or contamination of the sample?
Some ancient Native American genes have apparently gone extinct. mtDNA analysis of ancient Native American brains from Florida show genes that may have been lost from the Americas (Schurr et al., 1990, p. 619; see also Pääbo et al., 1988). Similar conclusions come from analysis of blood groups. Genes for the B and AB blood types have been largely lost in the Americas, but these genes were present in pre-Columbian humans in Peru. The blood groups found among modern Native Americans led A.E. Mourant (1983, p. 109) to state that:
the Amerinds appear to have possessed only the A and O genes before the coming of the Europeans. South of the USA-Mexican border only O appears to have been present. Most if not all the B genes in the northern zone and the A and B in the south can be accounted for by interbreeding with post-Columbian immigrant populations from across the Atlantic, but it is possible that some of the A and B genes in Andean populations are due to trans-Pacific immigration.
Actually, non-O genes were certainly in the Andes before Columbus, based on the study of ancient Peruvian mummies by M.J. Allison et al. (1978), who found all ABO blood group types (A, B, AB, and O) in mummies dating from 3000 B.C. to 1400 A.D., but in mummies dating after that period to 1650 A.D. only types A and O were found in their work. Clearly, some genes were lost in the Americas.
One obvious source for genetic loss was the massive eradication of Native Americans following the European Conquest, particularly due to widespread disease introduced by the Europeans. Scholars estimate that over 90% of the indigenous inhabitants of the Americas were wiped out in the years following 1492. There is reason to believe that there was a loss in genetic diversity in the Americas due to "the 'bottleneck' introduced by the European colonization, which reduced the population to less than 5% of its original size" (Ribeiro-dos-Santos et al., 1997). For example, Ribeiro-dos-Santos (1996) examined mtDNA in ancient South American Amerindians and found that 39% of the samples were not in the four major mtDNA haplotypes that dominate modern Native Americans, and less than half of these other types could have been haplotype X (Ribeiro-dos-Santos et al., 1996 and 1997). They state that the evidence "permits us to suggest that, in addition to the postulated bottleneck effect during the migration from Asia to the Americas, the depopulation effect started by European colonization in the 16th century contributed to the reduction in genetic variability of Amerindians" (abstract, Ribeiro-dos-Santos et al., 1996). O'Rourke et al. (2000) also discuss the extinction of genes, noting that other authors have called the nineteenth century the "extinction period" for southern South America, and state that it "is not obvious that samples obtained from populations undergoing decimation and extinction would be representative of precontact groups. Indeed, reduced populated size during this period would be expected to be accompanied by reduced genetic variability" (p. 232).
This is a key issue: it appears that mtDNA haplotypes other than A, B, C, D, or X may have been selectively lost or greatly reduced in extent by the massive depopulation of Native Americans. Monsalve (1997) also discusses several other studies supporting the concept of other ancient haplotypes in the Americas. Thus, there is a possible disconnect between modern DNA studies of surviving populations and ancient Native Americans.
Finally, for both mtDNA and Y-chromosome analysis, we need to realize that the science of human origins is still in its infancy. Rather than having firmly settled the nature of ancient human migrations with DNA studies, science is just scratching the surface, leaving many questions unanswered. Patience!