Natives or Immigrants: Modern Human Origin in East Asia

East Asia is one of the few regions in the world where a relatively large number of human fossils have been unearthed — a discovery that has been taken as evidence for an independent local origin of modern humans outside of Africa. However, genetic studies conducted in the past ten years, especially using Y chromosomes, have provided unequivocal evidence for an African origin of East Asian populations. The genetic signatures present in diverse East Asian populations mark the footsteps of prehistoric migrations that occurred tens of thousands of years ago.

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A SYNOPSIS OF EXTANT Y CHROMOSOME DIVERSITY IN EAST ASIA AND OCEANIA

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Homo erectus in East Asia: Human Ancestor or Evolutionary Dead-End?

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Using mitochondrial and nuclear DNA markers to reconstruct human evolution

Molecular genetic data have greatly improved our ability to test hypotheses about human evolution. During the past decade, a large amount of nuclear and mitochondrial data have been collected from diverse human populations. Taken together, these data indicate that modern humans are a relatively young species. African populations show the largest amount of genetic diversity, and they are the most genetically divergent population. Modern human populations expanded in size first on the African continent. These findings support a recent African origin of modern humans, but this conclusion should be tempered by the possible effects of factors such as gene flow, population size differences, and natural selection.

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Recent African origin of modern humans revealed by complete sequences of hominoid mitochondrial DNAs

We analyzed the complete mitochondrial DNA (mtDNA) sequences of three humans (African, European, and Japanese), three African apes (common and pygmy chimpanzees, and gorilla), and one orangutan in an attempt to estimate most accurately the substitution rates and divergence times of hominoid mtDNAs. Nonsynonymous substitutions and substitutions in RNA genes have accumulated with an approximately clock-like regularity. From these substitutions and under the assumption that the orangutan and African apes diverged 13 million years ago, we obtained a divergence time for humans and chimpanzees of 4.9 million years. This divergence time permitted calibration of the synonymous substitution rate (3.89 x 10(-8)/site per year). To obtain the substitution rate in the displacement (D)-loop region, we compared the three human mtDNAs and measured the relative abundance of substitutions in the D-loop region and at synonymous sites. The estimated substitution rate in the D-loop region was 7.00 x 10(-8)/site per year. Using both synonymous and D-loop substitutions, we inferred the age of the last common ancestor of the human mtDNAs as 143,000 +/- 18,000 years. The shallow ancestry of human mtDNAs, together with the observation that the African sequence is the most diverged among humans, strongly supports the recent African origin of modern humans, Homo sapiens sapiens.

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Ice Ages and the mitochondrial DNA chronology of human dispersals: a review

Modern DNA, in particular maternally inherited mitochondrial DNA (mtDNA), is now routinely used to trace ancient human migration routes and to obtain absolute dates for genetic prehistory. The errors on absolute genetic dates are often large (50% or more) and depend partly on the inherent evolutionary signal in the DNA data, and partly on our imperfect knowledge of the DNA mutation rate. Despite their imprecision, the genetic dates do provide an independent, consistent and global chronology linking living humans with their ancestors. Combining this chronology with archaeological and climatological data, most of our own mtDNA studies during the past decade strongly imply a major role for palaeoclimate in determining conditions for prehistoric migrations and demographic expansions. This paper summarizes our interpretation of the genetic findings, covering the initial and modest spread of humans within Africa more than 100 ka, the striking re-expansion within Africa 60–80 ka, leading ultimately to the out-of-Africa migration of a single, small group which settled in Australia, Eurasia and America during windows of opportunity at least partly dictated by fluctuations in sea-levels and climatic conditions.

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Understanding Human DNA Sequence Variation

Over the past century researchers have identified normal genetic variation and studied that variation in diverse human populations to determine the amounts and distributions of that variation. That information is being used to develop an understanding of the demographic histories of the different populations and the species as a whole, among other studies. With the advent of DNA-based markers in the last quarter century, these studies have accelerated. One of the challenges for the next century is to understand that variation. One component of that understanding will be population genetics. We present here examples of many of the ways these new data can be analyzed from a population perspective using results from our laboratory on multiple individual DNA-based polymorphisms, many clustered in haplotypes, studied in multiple populations representing all major geographic regions of the world. These data support an ‘‘out of Africa’’ hypothesis for human dispersal around the world and begin to refine the understanding of population structures and genetic relationships. We are also developing baseline information against which we can compare findings at different loci to aid in the identification of loci subject, now and in the past, to selection (directional or balancing). We do not yet have a comprehensive understanding of the extensive variation in the human genome, but some of that understanding is coming from population genetics.

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Has the Combination of Genetic and Fossil Evidence Solved the Riddle of Modern Human Origins?

Debate over the origin of modern humans continues without a clear end in sight. Currently, the genetic and fossil evidence is still used to support two different interpretations of the origin of modern humans. Some researchers claim that the genetic evidence is compatible with either an Out-of-Africa or a Multiregional model, while other scientists argue that the evidence supports only a Multiregional model of evolution. I argue that the fossil record and archeological evidence constrain interpretation of the genetic evidence and imply that very little, if any, admixture with Eurasian archaic hominins such as the Neanderthals occurred during the spread of modern humans out of Africa.

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The Y Chromosome Pool of Jews as Part of the Genetic Landscape of the Middle East

A sample of 526 Y chromosomes representing six Middle Eastern populations (Ashkenazi, Sephardic, and Kurdish Jews from Israel; Muslim Kurds; Muslim Arabs from Israel and the Palestinian Authority Area; and Bedouin from the Negev) was analyzed for 13 binary polymorphisms and six microsatellite loci. The investigation of the genetic relationship among three Jewish communities revealed that Kurdish and Sephardic Jews were indistinguishable from one another, whereas both differed slightly, yet significantly, from Ashkenazi Jews. The differences among Ashkenazim may be a result of low-level gene flow from European populations and/or genetic drift during isolation. Admixture between Kurdish Jews and their former Muslim host population in Kurdistan appeared to be negligible. In comparison with data available from other relevant populations in the region, Jews were found to be more closely related to groups in the north of the Fertile Crescent (Kurds, Turks, and Armenians) than to their Arab neighbors. The two haplogroups Eu 9 and Eu 10 constitute a major part of the Y chromosome pool in the analyzed sample. Our data suggest that Eu 9 originated in the northern part, and Eu 10 in the southern part of the Fertile Crescent. Genetic dating yielded estimates of the expansion of both haplogroups that cover the Neolithic period in the region. Palestinian Arabs and Bedouin differed from the other Middle Eastern populations studied here, mainly in specific high-frequency Eu 10 haplotypes not found in the non-Arab groups. These chromosomes might have been introduced through migrations from the Arabian Peninsula during the last two millennia. The present study contributes to the elucidation of the complex demographic history that shaped the present-day genetic landscape in the region.

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High-resolution Y chromosome haplotypes of Israeli and Palestinian Arabs reveal geographic substructure and substantial overlap with haplotypes of Jews

High-resolution Y chromosome haplotype analysis was performed in 143 paternally unrelated Israeli and Palestinian Moslem Arabs (I&P Arabs) by screening for 11 binary polymorphisms and six microsatellite loci. Two frequent haplotypes were found among the 83 detected: the modal haplotype of the I&P Arabs (~14%) was spread throughout the region, while its one-step microsatellite neighbor, the modal haplotype of the Galilee sample (~8%), was mainly restricted to the north. Geographic substructuring within the Arabs was observed in the highlands of Samaria and Judea. Y chromosome variation in the I&P Arabs was compared to that of Ashkenazi and Sephardic Jews, and to that of North Welsh individuals. At the haplogroup level, defined by the binary polymorphisms only, the Y chromosome distribution in Arabs and Jews was similar but not identical. At the haplotype level, determined by both binary and microsatellite markers, a more detailed pattern was observed. Single-step microsatellite networks of Arab and Jewish haplotypes revealed a common pool for a large portion of Y chromosomes, suggesting a relatively recent common ancestry. The two modal haplotypes in the I&P Arabs were closely related to the most frequent haplotype of Jews (the Cohen modal haplotype). However, the I&P Arab clade that includes the two Arab modal haplotypes (and makes up 32% of Arab chromosomes) is found at only very low frequency among Jews, reflecting divergence and/or admixture from other populations.

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The Two Common Mutations Causing Factor XI Deficiency in Jews Stem From Distinct Founders: One of Ancient Middle Eastern Origin and Another of More Recent European Origin

Previous studies showed that factor XI (FXI) deficiency commonly observed in Ashkenazi Jews is caused by two similarly frequent mutations, type II (Glu117stop) and type III (Phe283Leu) with allele frequencies of 0.0217 and 0.0254, respectively. In Iraqi Jews, who represent the ancient gene pool of Jews, only the type II mutation was observed with an allele frequency of 0.0167. In this study we sought founder effects for each mutation by examination of four FXI gene polymorphisms enabling haplotype analysis in affected Jewish patients of Ashkenazi, Iraqi, and other origins and in Arab patients. Initial population surveys of 387 Middle Eastern Jews (excluding Iraqi Jews), 560 North African/Sephardic Jews, and 382 Arabs revealed allele frequencies for the type II mutation of 0.0026, 0.0027, and 0.0065, respectively. In contrast, the type III mutation was not detected in any of these populations. All 60 independent chromosomes bearing the type III mutation were solely observed in Ashkenazi Jewish patients and were characterized by a relatively rare haplotype. All 103 independent chromosomes bearing the type II mutation in patients of Ashkenazi, Iraqi, Yemenite, Syrian, and Moroccan Jewish origin and of Arab origin were characterized by another distinct haplotype that was rare among normal Ashkenazi Jewish, Iraqi Jewish, and Arab chromosomes. These findings constitute the first example of a mutation common to Ashkenazi Jews, non-Ashkenazi Jews, and Arabs and are consistent with the origin of type II mutation in a founder before the divergence of the major segments of Jews. Our findings also indicate that the type III mutation arose more recently in an Ashkenazi Jewish individual.

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The Natural History of Ashkenazi Intelligence

We develop the hypothesis that the unique demography and sociology of Ashkenazim in medieval Europe selected for intelligence. Ashkenazi literacy, economic specialization, and closure to inward gene flow led to a social environment in which there was high fitness payoff to intelligence, specifically verbal and mathematical intelligence but not spatial ability. As with any regime of strong directional selection on a quantitative trait, genetic variants that were otherwise fitness reducing rose in frequency. In particular we propose that the well-known clusters of Ashkenazi genetic diseases, the sphingolipid cluster and the DNA repair cluster in particular, increase intelligence in heterozygotes. Other Ashkenazi disorders are known to increase intelligence. Although these disorders have been attributed to a bottleneck in Ashkenazi history and consequent genetic drift, there is no evidence of any bottleneck. Gene frequencies at a large number of autosomal loci show that if there was a bottleneck then subsequent gene flow from Europeans must have been very large, obliterating the effects of any bottleneck. The clustering of the disorders in only a few pathways and the presence at elevated frequency of more than one deleterious allele at many of them could not have been produced by drift. Instead these are signatures of strong and recent natural selection.

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Reconstruction of Patrilineages and Matrilineages of Samaritans and Other Israeli Populations From Y-Chromosome and Mitochondrial DNA Sequence Variation

The Samaritan community, which numbered more than a million in late Roman times and only 146 in 1917, numbers today about 640 people representing four large families. They are culturally different from both Jewish and non-Jewish populations in the Middle East and their origin remains a question of great interest. Genetic differences between the Samaritans and neighboring Jewish and non-Jewish populations are corroborated in the present study of 7,280 bp of nonrecombining Y-chromosome and 5,622 bp of coding and hypervariable segment I (HVS-I) mitochondrial DNA (mtDNA) sequences. Comparative sequence analysis was carried out on 12 Samaritan Y-chromosome, and mtDNA samples from nine male and seven female Samaritans separated by at least two generations. In addition, 18–20 male individuals were analyzed, each representing Ethiopian, Ashkenazi, Iraqi, Libyan, Moroccan, and Yemenite Jews, as well as Druze and Palestinians, all currently living in Israel. The four Samaritan families clustered to four distinct Y-chromosome haplogroups according to their patrilineal identity. Of the 16 Samaritan mtDNA samples, 14 carry either of two mitochondrial haplotypes that are rare or absent among other worldwide ethnic groups. Principal component analysis suggests a common ancestry of Samaritan and Jewish patrilineages. Most of the former may be traced back to a common ancestor in the paternally-inherited Jewish high priesthood (Cohanim) at the time of the Assyrian conquest of the kingdom of Israel.

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Testing hypotheses of language replacement in the Caucasus: evidence from the Y-chromosome

A previous analysis of mtDNA variation in the Caucasus found that Indo-European-speaking Armenians and Turkic-speaking Azerbaijanians were more closely related genetically to other Caucasus populations (who speak Caucasian languages) than to other Indo-European or Turkic groups, respectively. Armenian and Azerbaijanian therefore represent language replacements, possibly via elite dominance involving primarily male migrants, in which case genetic relationships of Armenians and Azerbaijanians based on the Y-chromosome should more closely reflect their linguistic relationships. We therefore analyzed 11 bi-allelic Y-chromosome markers in 389 males from eight populations, representing all major linguistic groups in the Caucasus. As with the mtDNA study, based on the Y-chromosome Armenians and Azerbaijanians are more closely-related genetically to their geographic neighbors in the Caucasus than to their linguistic neighbors elsewhere. However, whereas the mtDNA results show that Caucasian groups are more closely related genetically to European than to Near Eastern groups, by contrast the Y-chromosome shows a closer genetic relationship with the Near East than with Europe.

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Mitochondrial DNA variation and language replacements in the Caucasus

Sequences of the first hypervariable segment of the mitochondrial DNA (mtDNA) control region were obtained from 353 individuals representing nine groups and four major linguistic families (Indo-European, Altaic and North and South Caucasian) of the Caucasus region. The diversity within and between Caucasus populations exceeded the diversity within Europe, but was less than that in the Near East. Caucasus populations occupy an intermediate position between European and Near Eastern populations in tree and principal coordinate analyses, suggesting that they are either ancestral to European populations or derived via admixture from European and Near Eastern populations. The genetic relationships among Caucasus populations reflect geographical rather than linguistic relationships. In particular, the Indo-European-speaking Armenians and Altaic-speaking Azerbaijanians are most closely related to their nearest geographical neighbours in the Caucasus, not their linguistic neighbours (i.e. other Indo-European or Altaic populations). The mtDNA evidence thus suggests that the Armenian and Azerbaijanian languages represent instances of language replacement that had little impact on the mtDNA gene pool.

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Alu insertion polymorphisms and the genetic structure of human populations from the Caucasus

An analysis of 8 Alu insertion loci (ACE, TPA25, PV92, APO, FXIIIB, D1, A25, B65) has been carried out in six populations from the Caucasus, including Indo-European-speaking Armenians; Altaic-speaking Azerbaijanians; North Caucasian-speaking Cherkessians, Darginians, and Ingushians; and South Caucasian (Kartvelian)-speaking Georgians. The Caucasus populations exhibit low levels of within-population variation and high levels of between-population differentiation, with the average F_st value for the Caucasus of 0.113, which is almost as large as the F_st value of 0.157 for worldwide populations. Maximum likelihood tree and principal coordinate analyses both group the Caucasus populations with European populations. Neither geographic nor linguistic relationships appear to explain the genetic relationships of Caucasus populations. Instead, it appears as if they have been small and relatively isolated, and hence genetic drift has been the dominant influence on the genetic structure of Caucasus populations.

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Mitochondrial DNA and Y-Chromosome Variation in the Caucasus

We have analyzed mtDNA HVI sequences and Y chromosome haplogroups based on 11 binary markers in 371 individuals, from 11 populations in the Caucasus and the neighbouring countries of Turkey and Iran. Y chromosome haplogroup diversity in the Caucasus was almost as high as in Central Asia and the Near East, and significantly higher than in Europe. More than 27% of the variance in Y-haplogroups can be attributed to differences between populations, whereas mtDNA showed much lower heterogeneity between populations (less then 5%), suggesting a strong influence of patrilocal social structure. Several groups from the highland region of the Caucasus exhibited low diversity and high differentiation for either or both genetic systems, reflecting enhanced genetic drift in these small, isolated populations. Overall, the Caucasus groups showed greater similarity with West Asian than with European groups for both genetic systems, although this similarity was much more pronounced for the Y chromosome than for mtDNA, suggesting that male-mediated migrations from West Asia have influenced the genetic structure of Caucasus populations.

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Genetics and Population History of Caucasus Populations

We describe aspects of genetic diversity in several ethnic populations of the Caucasus of Daghestan using mitochondrial DNA sequences and a sample of 100 polymorphic ALU insertion loci. The mitochondrial DNA sequences are like those of Europe. Principal coordinates and nearest neighbor statistics show that there is little detectable structure in the distances among populations computed from mtDNA. The ALU frequencies of the Caucasus populations suggest that they have undergone more genetic drift than most other groups since the dispersal of modern humans. Genetic differences among these populations are not large; instead they are of the same order as distances among populations of Europe. We compare two methods of inference about the demography of ancient colonizing populations from Africa, one based on conventional Fst statistics and one based on mean ALU insertion frequencies. The two approaches agree reasonably well if we assume that there was demographic growth in Africa before the diaspora of ancestors of contemporary regional human groups outside Africa.

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