Genomic Data Reveal a Complex Making of Humans

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Genomic Data Reveal a Complex Making of Humans Jan 3, 2014 16:15:54 GMT

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Post by Admin on Jan 3, 2014 16:15:54 GMT

In a new article published in Molecular Biology and Evolution, authors Jin, et. al., present evidence for the accumulation of a Neanderthal DNA region found on chromosome 3 that contains 18 genes, with several related to UV-light adaptation, including the Hyal2 gene. Their results reveal this region was positively selected and enriched in East Asians, ranging from up to 49 percent in Japanese to 66 percent in Southern Chinese. The new paper (Ding et al. 2013) argues that Neanderthal introgression into European populations resulted from East Asian gene flow. Haplogroup NO of the Finno-Ugric peoples and their descendants spread from Northern China about 12,000–14,000 years ago and haplogroup N is a descendant of Haplogroup NO, which is the most common haplogroup among the Finns (60%) and can also be found at high frequencies in Russia. Most of the Finno-Ugric speaking populations possess amalgamation of West and East Eurasian gene pools supporting the idea of mixed origins in these modern populations as the photo below suggests. The Altai region may have served as the launching point for Neanderthal genes to spread among modern humans and Neanderthal/H. sapience admixture could have occurred exclusively in the region. Ancient Asian migrants who carried haplogroup N could also have spread Neanderthal DNA in Northern Europe, thus making modern European populations around 2-3% Neanderthal.

Two Khanty women in Man uskve nomad camp, Berezovsky, Khanty-Mansia, Russia

Studies of the Neanderthal and Denisovan genomes demonstrate archaic hominin introgression in Eurasians. Here we present evidence of Neanderthal introgression within the chromosome 3p21.31 region, occurring with a high frequency in East Asians (ranging from 49.4% to 66.5%) and at a low frequency in Europeans. We also detected a signal of strong positive selection in this region only in East Asians. Our data indicate that likely candidate targets of selection include rs12488302-T and its associated alleles—among which four are non-synonymous, including rs35455589-G in HYAL2, a gene related to the cellular response to ultraviolet-B irradiation. Furthermore, suggestive evidence supports latitude-dependent selection, implicating a role of ultraviolet-B. Interestingly, the distribution of rs35455589-G suggests that this allele was lost during the exodus of ancestors of modern Eurasians from Africa, and reintroduced to Eurasians from Neanderthals.

Studies of mitochondrial and Y chromosome DNA have provided solid evidence supporting an African origin for all modern Eurasians—known as the out-of-Africa theory of modern human origins (Cann et al. 1987; Hammer et al. 1995). The recent publication of the Neanderthal and Denisovan genomes enables direct comparison between modern human genomes and archaic hominin genomes. Examinations of archaic hominin genomes reveal Neanderthal introgression among modern Eurasians (Green et al. 2010), and Denisovan introgression in modern Oceanians (Reich et al. 2010), but their contributions to modern humans are very limited. Abi-Rached et al. (2011) identified Neanderthal and Denisovan introgression at the HLA loci (MIM142800, 142830, 142840), and suggested that theintrogressed alleles significantly re-shaped the immune system of modern humans, especially those outside Africa. Mendez et al. (2013) found both Neanderthal and Denisovan introgression around the OAS gene cluster (MIM 164350, 603350, and 603351). Mendez et al. (2012b) also found both Neanderthal and Denisovan introgression in the region surrounding STAT2 (MIM 600556). Notably, the results of a neutrality test on the STAT2 region suggest that Neanderthal introgression is under positive natural selection among Papua New Guineans.

In the present study, we analyzed a region of the chromosome 3p21.31 (denoted as the HYAL region), which encompasses eighteen genes, including HYAL1 (MIM 607071), HYAL2 (MIM 603551), and HYAL3 (MIM 604038). These three HYAL genes encode hyaluronoglucosaminidases, which are involved in the cellular response to ultraviolet-B (UV-B). We analyzed data from the 1000 Genomes Project (1KG) Phase 1 (The 1000 Genomes Consortium, 2012)and found archaic hominin introgression in the genomes of contemporary Eurasians, with East Asians showing a high frequency of introgressive haplotypes, ranging from 49.4% in a Japanese population to 66.5% in a Southern Han Chinese population. Both the integrated haplotype score (iHS) and the composite of multiple signals (CMS) tests also revealed a signal of strong positive selection among East Asians. The target of this selection appears to be rs12488402-T—which is exclusively carried by the introgressive haplotypes—or one of the four non-synonymous single-nucleotide polymorphisms (SNPs) found to be in strong linkage disequilibrium (LD) with rs12488302. To conclude, the HYAL region is identified as showing archaic hominin introgression with the introgressive haplotypes under positive selection in East Asian populations.

A phylogenetic tree was reconstructed using all non-recombinant haplotypes of contemporary populations, Altai Neanderthal, and Denisovan, using chimpanzee as outgroup (fig. 2). Trivial monophyletic clusters were collapsed to simplify presentation without losing major structures of the tree. The phylogenetic tree shows that some haplotypes of contemporary populations coalesce first with archaic hominins (Altai Neanderthal and Denisovan) before joining with the rest of the haplotypes of contemporary populations, suggesting archaic hominin introgression. This is supported by the bootstrap value of 98 at Node A in figure 2, which separates all archaic/introgressive haplotypes from other haplotypes of contemporary populations. The introgressive haplotypes first coalesce with Altai Neanderthals (bootstrap value = 99), then with Denisovan (bootstrap value = 96), indicating that Neanderthal is more likely to be the source of introgression than Denisovan. We inferred the ancestral sequence of all introgressive haplotypes using a maximum likelihood procedure implemented in MEGA 5 (Tamura et al. 2011), and further compared it with archaic genomes. The ancestral sequence of introgressive haplotypes shares 99.3% (731/736) of alleles with Altai Neanderthal, 98.6% (726/736) with Vindija Neanderthal, and 97.2% (716/736) with Denisovan. This result also supports that the introgressive haplotypes observed in contemporary populations are closer to Neanderthal than Denisovan.

In addition to this phylogenetic approach, we also searched for Type 2 derived alleles on the putative introgressive haplotypes (see Material and Methods). Type 2 derived alleles were originated from mutations in the archaic hominin linage after their divergence withancestors of modern humans. We obtained the polymorphism table for all non-recombinant haplotypes (supplementary table S5). We found that the Type 2 derived alleles existed in the putative introgressive haplotypes, which fit the allele pattern of introgressive haplotypes. Furthermore, of the Type 2 alleles, 90.3% (28/31) are identical to the Altai Neanderthal alleles and 16.1% (5/31) to the Denisovan alleles. This suggests that the putative introgressive haplotypes are not false positives originated inside the modern human linage, since the haplotypes of contemporary populations would have similar sequence divergence with Neanderthal and Denisovan. Additionally, the high sequence similarity to Neanderthal indicates a likelihood that the putative introgressive haplotypes are of Neanderthal origin.

The 1KG and the International Haplotype Map Project Phase 3 (HapMap 3; the International HapMap 3 Consortium, 2010) datasets were used to investigate the global distribution of introgressive haplotypes. We observed high frequencies of the introgressive haplotypes in East Asian populations, ranging from 49.4% in JPT to 66.5% in the Han Chinese from Southern China (CHS; fig. 3, supplementary table S2), consistent with the pattern observed in figure 2. The introgressive haplotypes are also present at low frequencies in CEU (0.57%, a singleton), in the British population in England and Scotland (GBR; 0.56%, a singleton), and in the Finnish population in Finland (FIN; 3.7%, 7 haplotypes), as well as in four New World populations, including the population with Mexican Ancestry in Los Angeles, CA (MXL; 34.8%), Puerto Ricans in Puerto Rico (PUR; 11.8%), Columbians in Medellin, Columbia (CLM; 20.0%), and the population of Americans with African ancestry in the Southwest USA (ASW; 1.64%).

Since the frequency of introgressive haplotypes is higher in East Asians than in Europeans, it is possible that archaic introgression occurred in the ancestral population shared by East Asians and Native Americans, while the introgressive haplotypes in Europeans might be the result of recent gene flow from East Asia to Europe. To examine this hypothesis, we obtained the sequence of the 500-kb regions flanking the HYAL region to the left and right (chr3: 49,725,029–50,225,028 and chr3: 50,420,555–50,920,554) for Eurasians. We divided the Eurasian haplotypes into four groups: (1) European non-introgressive haplotypes (EUR-N); (2) European introgressive haplotypes (EUR-I); (3) East Asian non-introgressive haplotypes (ASN-N); and (4) East Asian introgressive haplotypes (ASN-I). If the introgressive haplotypes in Europeans resulted from East Asian gene flow, the flanking regions should be more similar to East Asians than to Europeans. We calculated the average sequence similarities among the four groups (supplementary table S7), analyzing a total of 9180 polymorphic sites. Interestingly, EUR-I shows significantly higher sequence similarity with ASN-N (0.9611) and ASN-I (0.9683) than with EUR-N (0.9538), with a P value of 0.0000 (right-tailed Student’s t-test). This observation is consistent with our hypothesis that the introgressive haplotypes in Europe resulted from recent East Asian gene flow.

Here we present evidence of the introgression of a Neanderthal segment encompassing 18 genes into the genomes of contemporary populations. We further find evidence that the introgressive haplotypes are subjected to strong positive selection in East Asian populations. Interestingly, the introgressive haplotypes are almost East Asian specific, except for some sporadic distribution in Europe and South Asia. Our findings suggest the introgression occurred within the ancestral population shared by East Asians and Native Americans, and the introgressive haplotypes in Europe resulted from recent East Asian gene flow. This “Asian-specific” Neanderthal introgression is consistent with a previous report of higher levels of Neanderthal ancestry in East Asians than in Europeans (Wall et al. 2013).

Interestingly, rs35455589, a non-synonymous SNP located in the fourth exon of HYAL2, is found to be in strong LD with rs12488302 (r2 = 0.97) in East Asian populations. Changing from ancestral allele (G) to derived allele (T) has resulted in the replacement of leucine with isoleucine at the 418th amino acid of HYAL2. In mice, all Hyal genes have four exons, and exons 2–4 show highest level of sequence conservation (Shuttleworth et al. 2002). Both SiPhy and GERP algorithms predicted rs35455589 as conservative. Furthermore, EHH analyses (fig. 4D, E, and F) revealed that rs35455589-G might be the target of positive selection.

Rs11130248-G (in strong LD with rs35455589-G, r2 = 1.00) has also been identified by a genome-wide association study as being related to keloid susceptibility in Japanese populations (Nakashima et al. 2010). Keloid results from overgrowth of granulation tissue, and is most prevalent in Africa and Asia. Reduced hyaluronan levels have been observed in keloid tissue (Meyer et al. 2000). Since HYAL2 encodes an enzyme that degrades hyaluronan, we suspect that the increased keloid risk in African and Asian populations might be related to the polymorphism at rs35455589, although the same allele had different evolutionary history in these two groups. Further studies should be carried out to focus on the effect of the allele change at rs35455589 on HYAL2 expression, hyaluronan metabolism, and keloid pathogenesis.

Ding, Qiliang, et al. "Neanderthal Introgression at Chromosome 3p21. 31 was Under Positive Natural Selection in East Asians." Molecular biology and evolution (2013): mst260.

Last Edit: Jan 4, 2014 6:16:05 GMT by Admin

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Genomic Data Reveal a Complex Making of Humans Jan 8, 2014 22:43:44 GMT

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Post by Admin on Jan 8, 2014 22:43:44 GMT

Canfield et al. (2013) found that the mutated segment of DNA was derived from two other mutated segments commonly found in East Asian populations and modern Europeans' genetic ancestry could be traced back to East Asians. The Kalash with blond hair or light eyes, who are residing in the Hindu Kush mountain range between central Afghanistan and northern Pakistan, were thought to have descended from the members of Alexander the Great's army but the Kalash could be the direct descendants of the proto-European population that had split from East Asians with the A111T mutation. It has also been found that 56 per cent of villagers in Liqian, on the fringes of the Gobi Desert in north-western China, were Caucasian in origin and the villagers may also be genetically related to the proto-European population who emerged in Asia, contrary to the speculation that he may be a descendant of Roman mercenaries who allegedly fought the Han Chinese 2,000 years ago. After the split, most of the proto-European population gradually left West Asia for Europe but some of them may have stayed behind as unique tribes.

A Kalash girl in Afghanistan.

A new study has shown how a specific mutation in the SLC24A5 gene provides evidence of shared ancestry of Asians with Europeans.

While the genetics of skin color is largely unclear, past research using zebrafish by Pennsylvania State University College of Medicine’s Keith Cheng identified that the SLC24A5 gene is a key contributor to the skin color difference between Europeans and West Africans.

In this study, Victor Canfield, assistant professor of pharmacology, together with Cheng, studied a specific mutation in SLC24A5, called A111T. The researchers found that all individuals from the Middle East, North Africa, East Africa and South India who carry the A111T mutation share a common “fingerprint” – traces of the ancestral genetic code – in the corresponding chromosomal region, indicating that all existing instances of this mutation originate from the same person.

The pattern of proportions of people with this lighter skin color mutation indicates that the A111T mutation occurred somewhere between the Middle East and the Indian subcontinent.
“This means that Middle Easterners and South Indians, which includes most inhabitants of India, Pakistan and Bangladesh, share significant ancestry,” said Cheng.

This mutated segment of DNA was itself created from a combination of two other mutated segments commonly found in Eastern Asians – traditionally defined as Chinese, Japanese and Korean. “The coincidence of this interesting form of evidence of shared ancestry of East Asians with Europeans, within this tiny chromosomal region, is exciting,” said Cheng. “The combining of segments occurred after the ancestors of East Asians and Europeans split geographically more than 50,000 years ago; the A111T mutation occurred afterward.”

These findings were reported in the journal G3. Cheng plans to next look at more genetic samples to better understand what genes play the most important role in East Asian skin color. He will then use zebrafish to test those suspected genes. The article can be found at: Canfield V et al. (2013) Molecular Phylogeography of a Human Autosomal Skin Color Locus Under Natural Selection.

Last Edit: Jan 2, 2019 21:57:24 GMT by Admin

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Genomic Data Reveal a Complex Making of Humans Jan 16, 2014 15:08:43 GMT

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Post by Admin on Jan 16, 2014 15:08:43 GMT

This expanded study of mtDNA and Y-chromosome variation in the Caucasus extends previous results (Nasidze et al. 2001, 2003). To increase the accuracy of measurements of genetic diversity among populations, it is desirable to increase the number of populations rather than the number of individuals per population (Nei, 1978; Pons & Petit, 1995). Therefore, we added 11 new populations to the 14 previously studied groups from the Caucasus, with overall sample sizes adequate for estimating genetic diversity (Nei, 1978; Pons & Petit, 1995). Overall, the Caucasus groups are genetically heterogeneous, suggesting large genetic differences among populations. More than 27% of the Y chromosome genetic variance occurs between populations, and 79.7% of the pairwise Fst values between populations are significantly different from zero (P < 0.05). By contrast, there is much lower heterogeneity between populations based on mtDNA; less than 5% of the mtDNA genetic variance occurs between populations, and 56.5% of the pairwise Fst values are significantly different from zero (P < 0.05).

One possible explanation for much lower Fst values for mtDNA than for the Y chromosome might be the difference in mutation rates, as the mtDNA HV1 sequences evolve much more rapidly than the Y-SNPs. However, differences in mutation rate will influence total levels of diversity, but not the apportioning of genetic diversity within vs. among populations, as measured by Fst values. Empirical evidence for this assertion was demonstrated recently by Excoffier & Hamilton (2003), who show that the components of genetic variance for global human populations due to variability between groups, between populations within groups, and between individual populations, did not differ for several genetic systems with widely varying mutation rates. A more likely explanation for the observed pattern of greater differentiation between Caucasus populations for the Y chromosome than for mtDNA, which is often observed in human populations (Seielstad et al. 1998), is a higher female migration rate due to patrilocality (Oota et al. 2001).

This genetic heterogeneity does not correlate with either linguistic diversity or geographic barriers in the Caucasus. In particular, Indo-European speaking Armenians and Turkic-speaking Azerbaijanians are genetically most closely related (for both mtDNA and the Y-chromosome) to other Caucasus groups and not to other Indo-European or Turkic-speaking groups (Figures 2A, 2B). Moreover, linguistic classifications of the Caucasus groups correspond poorly with their genetic structure (Table 4).

Although geographic classifications do provide a better fit to the genetic structure (Table 4), correlations between genetic and geographic distances between groups were statistically non-significant. We also did not detect any influence of the Caucasus Mountains as a significant geographic barrier; the average genetic distances between North and South Caucasus groups for mtDNA (Fst= 0.019) and Y-haplogroups (Fst= 0.190) were comparable to the average genetic distances within geographic groups (North Caucasus: mtDNA Fst= 0.024, Y-haplogroup Fst= 0.185; South Caucasus: mtDNA Fst= 0.026, Y-haplogroup Fst= 0.195). Instead, the spatial analysis of molecular variance (Figure 3 and Table 5) identified a few outlier populations for each genetic system that partially overlapped. Almost all of these outliers are small, isolated populations residing in the highland region of the Caucasus and hence are likely to have undergone genetic drift. In sum, there is no evidence that the Caucasus Mountains have served as a barrier to gene flow.

The primary difference between this study and previous studies lies in the genetic relationships of the Caucasus populations with European and West Asian populations. Previously, mtDNA indicated a closer relationship of the Caucasus with Europe (Nasidze et al. 2001), while the Y chromosome indicated a closer relationship with West Asia (Nasidze et al. 2003). However, the present study finds that the Caucasus is slightly closer genetically to West Asian than to European populations (Table 6) with respect to mtDNA. The reason for this discrepancy appears to be the inclusion of new data from Iranian (this study) and Kurdish (Comas et al. 2000) groups, which associate more closely with the Caucasus groups than do the previously studied West Asian groups (Figure 2A). When the Iranians and Kurds were removed from the analysis, Caucasian groups were much closer to European than to West Asian groups with respect to mtDNA (average Fst between Caucasus and West Asia is 0.033, vs. 0.021 between Caucasus and Europe). When we included these populations, the average Fst value between the Caucasus and West Asia dropped to 0.026. These results emphasize the importance of obtaining data from all relevant neighbouring groups when investigating the genetic relationships of Caucasus groups; we are currently expanding our sampling of Iranian and Kurdish groups to further study their relationships with the Caucasus groups.

With respect to the Y-chromosome relationships of the Caucasus with Europe and West Asia, the present study reinforces previous results (Nasidze et al. 2003) in that we find that the Caucasus are more closely related to West Asia than to Europe. In particular, the most common Y chromosome haplogroups in the Caucasus (F*, G* and J2*) are all probably of West Asian origin (Semino et al. 2000), suggesting a strong West Asian paternal influence on the Caucasus region. This interpretation is supported by the MDS plot based on Y-haplogroups (Figure 2b); Caucasus and West Asian groups are intermingled, whereas European populations form distinct and separate clusters. Moreover, these conclusions do not change when the South and North Caucasus are compared separately with Europe and West Asia; there are no significant differences between average pairwise Fst values for North and South Caucasus comparisons with Europe and West Asia (t-tests, t =−0.74, P = 0.466, and t =−2.86, P = 0.06 for comparing North vs. South Caucaus to West Asia and to Europe, respectively). We suggest that the Y-chromosome results may reflect recent “invading” migrations from the Near East that probably mostly involved males. Different Near Eastern groups invaded the Caucasus numerous times during the last two millennia, including the occupation of Georgia by Arab calips after 654 AD, the Seljuc Turks invasion of the South Caucasus in the 11th century, and repeated invasions by Turks and Persians (Muskhelishvili, 1977 and references therein).

To explain why mtDNA variation (but not the Y-chromosome) places the Caucasus in an intermediate position between Europe and West Asia, we suggest that this reflects a common ancestry of Caucasus and European populations. This common ancestry could date back to pre-Neolithic times, as suggested by Renfrew (Renfrew, 1992) who considered Caucasian languages to reflect human dispersal over 15,000 years ago. Or, it could reflect a route for Neolithic farmers from the Near East to Europe via the Caucasus. There are several securely-dated Neolithic sites in the Caucasus that are 6,000-7,000 years old (Masson & Merpert, 1982; Muskhelishvili, 1977), which pre-date or coincide with the appearance of agriculture in Europe. Regardless of whether the close relationship between European and Caucasian groups reflects pre-Neolithic or Neolithic events, more recent, primarily male-mediated migrations from West Asia to the Caucasus would have reduced the signature of a common Europe-Caucasus genetic ancestry for the Y-chromosome, but not for mtDNA (Nasidze et al. 2003).

In conclusion, the major aspect of the Caucasus population structure seems to be high overall levels of genetic differentiation, much higher for the Y chromosome than for mtDNA. The genetic structure of Caucasian groups is more accurately represented by geographic than linguistic classifications of populations. Overall, it appears that isolation and small population sizes, especially in the highland areas, have led to genetic drift and enhanced genetic differentiation. We also find evidence of different demographic histories for the Y chromosome vs. mtDNA, with the Y chromosome indicating a predominantly West Asian influence, whereas mtDNA variation in the Caucasus seems to reflect a more complex interaction of European and West Asian influences.

Nasidze, I., et al. "Mitochondrial DNA and Y‐chromosome variation in the Caucasus." Annals of human genetics 68.3 (2004): 205-221.

Last Edit: Jan 2, 2019 22:01:06 GMT by Admin

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Genomic Data Reveal a Complex Making of Humans Jan 17, 2014 4:39:48 GMT

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Post by Admin on Jan 17, 2014 4:39:48 GMT

Haplogroups: Their Phylogenesis and Geographic Distributions. The original nomenclature system of Y chromosome genotypes standardized in 2002 defined 18 haplogroups, labeled A through R (12). There are now 20 main haplogroups, designated A through T (13). Their basic phylogenetic relationships are shown in Fig. 1. Two deep branches, unifying haplogroups IJK and MNOPS, are shown. The geographic distributions of frequencies of each haplogroup were calculated on the basis of published data (listed in Table S1) and are shown in Fig. 2 for the 15 numerically and geographically most important haplogroups. The K, M, and S haplogroup distributions are not shown because they occupy rather unique space, mostly in Oceania. The F* and P* haplogroups are paraphyletic and often rare, except for F* in India, which codistributes with H, and are also omitted.

Fig. 1. Current phylogenetic relationships of the 20 major haplogroups of the global Y chromosome gene tree. Star denotes the new topology formed by the M522 and M523 SNPs that now join the previously independent IJ-M429 and KT-M9 haplogroups. Diamond indicates position of M526 SNP that now unifies haplogroups KMNOPS. M522,

Haplogroups A and B are the deepest branches in the phylogeny and are essentially restricted to Africa, bolstering the evidence that modern humans first arose there (14, 15). Haplogroup A is mainly found in the Rift Valley from Ethiopia to Cape Town, mostly but not exclusively in some of the oldest hunter-gatherers who still survive and speak Khoikhoi and San languages, proposed by some to be the oldest languages. The interruption of its distribution in the middle of the Rift Valley is possibly the consequence of replacement by Bantu-speaking farmers who settled the region starting in the first millennium of the Christian era. Haplogroup B is found mainly among African Pygmies, who live in the central African forest and are still predominantly hunters-gatherers but speak Bantu languages borrowed from farmers who arrived in the area between 2,000 and 3,000 years ago. The third predominantly African haplogroup, E, diversified some time afterward, probably descending from the East African population that generated the Out of Africa expansion. The geographic distributions of the major branches of this haplogroup, given in Fig. S1b, suggest that most of the settlement outside of Africa by haplogroup E members involves the later mutant E-M35 varieties like M78, M81, and M123 that extended to Arabia and the northern Mediterranean coast.

Although the precise phylogenetic relationships among haplogroups F–H remain uncertain (Fig. 1), 3 phylogenetic unifying relationships in the interior framework of the phylogeny reveal shared patterns of common molecular heritage. First, the CF-P143 common ancestor shows an ancient split from the DE-YAP clade, clarifying the earliest diversification events outside Africa (Fig. S2a). Second, the unification of haplogroups IJK by M522 and M523 now creates evolutionary distance from F–H representatives, as well as supporting the inference that both IJ-M429 (Fig. S3a) and KT-M9 arose closer to the Middle East than central Asia or eastern Asia. Third, the very successful and widespread MNOPS-M526 (Fig. S3a) ancestor indicates that haplogroups L and T have individual ancestry consistent with their current distinctive geography (Fig. S3a). The phylogeographic patterns shown in the 4 last rows in Fig. 2 are consistent with the Out of Africa expansion approximately 60,000 years ago, characterized by rapid dispersal across Eurasia and Oceania and followed by subsequent isolation (16).

Haplogroups G–J, T, and L generally are constrained geographically near Europe, the Middle East, and parts of western Asia with various extensions, especially to Arabia and India. Haplogroups D, H, T, and L have more localized distributions and often lower frequencies. The haplogroups with the greatest spatial distribution are those associated with widespread haplogroups NO and PQR ancestry. Haplogroup R peopled central and western Asia and a great part of Europe. Haplogroup N is frequent across boreal and northwest Asia and O in southeast Asia including the islands and part of New Guinea.

Haplogroups C and Q display Asian ancestry and hold the unique privilege of having settled America. Not surprisingly their origin seems to have been in northeast Asia. The absence of haplogroup N in the Americas indicates that its spread across Asia happened after the submergence of the Bering land bridge. It is likely that haplogroup C entered America after Q, even though C originated phylogenetically earlier than Q. In fact, C is found only in the northern part of North America, limited to the area where the family of languages by American Indians called Na-Dene (17) is spoken.

Inferring the Place of Origin of Haplotypes or Haplogroups. Haplogroup centroids with their standard deviations are given in Tables S2 and S3 and their location in Fig. S4b. Standard deviations measure the spread of each haplogroup as average distance from the mean and are calculated on straight-line distances from the means. Several geographic distributions have multiple modes. These may be due to geographic barriers and/or secondary migrations or expansions, but also to later arrivals of other haplogroups that replaced/displaced earlier settlements in the regions between 2 widely separated modes. This may have happened specifically, for instance for haplogroup A, which probably at the beginning occupied continuously the Ethiopia–South Africa region, but in the first millennium after Christ much of it was subsequently replaced because of occupation by various waves of expanding Bantu farmers from Cameroon across all southern Africa. Another phenomenon is the presence of small propagules far away from the rest of the distribution, as in haplogroups B, G, I, J, L, H, and Q. In part this phenomenon is due to the small size of many samples. Sometimes there is complete geographic separation between areas showing fairly important presence of the haplogroup, as in G, H, Q, and T. For example, haplogroup H in Europe is often confined to ethnic Roma. Another phenomenon possibly responsible for some of these irregularities, especially in the early part of the expansion, is the surfing effect described later.

If migrations were random, the geographic distribution of individuals with a specific haplogroup would be approximately normal (Gaussian) around the place of origin of the oldest mutation defining the haplogroup, apart from irregularities due to vagaries of the environment: obstacles, like mountains and deserts, or favored routes, like coasts and rivers. Below we list the most prominent 16 haplogroups by the number of major modes (i.e., the local geographic maxima of the gene frequencies of each haplogroup), which are easily observable on the maps as the darkest blue areas (Fig. 2): haplogroups B, D, G, J, L, M, and O are largely unimodal geographically, apart from isolated propagules (e.g., in B). The presence of haplogroup O in remote Madagascar is consistent with a well-known part of the Polynesian expansion. Most of these haplogroups have a clear, major mode and a relatively symmetric geographic distribution around it. Some like G, L, S, M, and T do not reach very high frequencies and/or have a very limited geographic distribution. Haplogroups A, E, and H are sharply bimodal, whereas C, I, N, Q, R, and T are clearly multimodal and several of them have a wide and abundant world representation. By subdividing each haplogroup into a tree showing the geographic distributions of its subclades, one can distinguish within-haplogroup paths of expansions and their mutational hierarchy. Examples are shown in Figs. S1–S3, S4a, and S5 for the most interesting cases of complicated distributions: A, B, E, I, J, O, and R. Even for superficially unimodal haplogroups like J and R this analysis reveals interesting complexity. The similarity of patterns of different mutants indicates some secondary expansions. It is also interesting to sum the distributions of different haplogroups descending from the same mutation, as for example D and E, which both descend from DE-YAP, the first mutation that split into the E branch that perhaps returned to Africa (or arose there), whereas the other branch, D, is found today mainly in the Himalayas and Japan.

For unimodal haplogroups, centroids are not far from the modes of the geographic distribution of the population represented by the haplogroup. Their approximately spatial (bidimensional) Gaussian distribution suggests that the populations carrying the haplogroup may have expanded relatively slowly and relatively homogenously in all directions around their place of origin. This is more likely to happen if the local environment has no major barriers or irregularities. Under these assumptions, the centroid or the mode or some intermediate position are reasonable estimates of the place of origin of the earliest mutation(s) marking the haplogroup. Such a geographic assignment of the place of origin of the mutation leading each haplogroup allows superimposing a phylogenetic tree on a geographic map of the origin of each haplogroup, producing an approximate space and time display of major migrations of the human species in the past.

DNA variation among human populations seems to have less adaptive significance than drift, reinforcing earlier results (10, 11). On the other hand, natural selection has favored an enormous advance to our species in competition with other species, allowing a sheer numbers increase by a factor of ≈1,000 (32) between approximately 60,000 and 10,000 years ago, because of expansion of a small African tribe to the whole world, and another 1,000× factor because of the transition from food collection to food production initiated probably independently in several parts of the world, beginning 12,000 to 6,000 years ago, which involved many new challenges probably very different from place to place. There is wide agreement that the first phase was due to the generalization of linguistic skills, favoring sociological developments and, with it, very rapid spread of innovations, and another type of cultural evolution that became even stronger, although more localized, with the exploitation of local domesticated plants and animals. One would expect little increase of genetic variation between populations in the first phase, except for some adaptation to different climates (which was, however, often met by cultural adaptations like housing and clothing). There probably was more need of biologic adaptations, and therefore of natural selection in the second phase, to meet challenges due to profound differences in diet and increased contact with domesticated animals and their contagious diseases. Examples in different parts of the world are pigmentation (33), lactose tolerance (34–36), and increase of genetic resistances to malaria (37, 38). Cultural evolution became much more effective than biologic evolution in meeting perceived needs, and may have almost replaced it, but every novelty has costs in addition to benefits, and thus much of natural selection may now be directed to take care of specific costs generated by cultural evolution, which were, however, not too severe, at least so far.

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Genomic Data Reveal a Complex Making of Humans Jan 17, 2014 21:29:45 GMT

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Post by Admin on Jan 17, 2014 21:29:45 GMT

Although the frequency of R1 lineages is currently the highest in Europe, the phylogeographic argument for their origin outside Europe, likely somewhere in West Asia, arises from the geographic distribution of the primary splits in the R1 phylogeny: at least three basic R-M207-derived haplogroups – R1a-M420*, R1b-M343* and R2 – occur mostly outside Europe. Figure 1b shows approximate locations of the 118 populations studied and proportional sample sizes. As the intensity of sampling is thin relative to the expanse of West Asia, the spatial-frequency surfaces for this region should be viewed as preliminary. Of the total of 193 R1b-M73 chromosomes detected, all except two Russians occurred outside Europe, either in the Caucasus, Turkey, the Circum-Uralic and North Pakistan regions (Figure 1c), in contrast to its considerably more widespread companion R1b-M269 clade (Figure 1d). With the exception of rare incidences of R1b-V88 in Corsica, Sardinia13 and Southern France (Supplementary Table S4), there is nearly mutually exclusive patterning of V88 across trans-Saharan Africa vs the prominence of P297-related varieties widespread across the Caucasus, Circum-Uralic regions, Anatolia and Europe. The detection of V88 in Iran, Palestine and especially the Dead Sea, Jordan (Supplementary Table S4) provides an insight into the back to Africa migration route.

(a) Phylogenetic relationships of haplogroup R binary polymorphisms studied. The names of six polymorphisms whose phylogenetic positions were determined in representative-derived samples, but not surveyed in the entire sample collection are indicated in italics. Dashed lines indicate basal haplogroup branches that were not observed. The YCC nomenclature labels reflect the exclusion of the P25 SNP from the phylogeny given its innate instability.44 The asterisk (*) refers to the unresolved status of the phylogenetic haplogroups beyond the specified marker. (b) Approximate locations of the 118 studied populations appear as circles on the map that are proportional to sample sizes, the smallest n=9 and the largest n=522. (c–o). Spatial-frequency distributions of haplogroup-frequency data. Each map was obtained by applying the frequencies from Supplementary Table S4 for 10355 individuals distributed in 118 population samples that are either new or updated to the present phylogenetic-resolution level from literature (references listed in the Supplementary Table 4) plus R-M269 data from Cruciani et al13 for North African points. Data concerning the strong U152 founder effect signal with identical haplotypes in Northern Bashkirs is excluded from the plots. The frequency data were converted to spatial-frequency maps using Surfer software (version 7, Golden software Inc., Cold Spring Harbor, NY, USA), following the Kriging procedure.

The frequency data for 13 major R1b1-P297 components with minimum frequency ≥10% were used to create spatial distribution maps (Figure 1c–o), whereas the phylogenetic relationships of the haplogroups are shown in Figure 1a. Besides the obvious differences in the geographic spreads of the M73, M269 and V88 branches that stem out of the R1b-M343 node as noted above, there are apparent geographic patterns also in the downstream branches, between markers M412 and M222 (Figure 1f–o). Although it is likely that additional sub-haplogroups within the more numerous L23*(xM412) assemblage currently remain hidden, it is instructive that these chromosomes often exceed 10% frequency in the Caucasus, Turkey and some SE Europe and Circum-Uralic populations (Supplementary Table S4; Figure 1e), whereas conversely they typically display frequencies ≤5% in Western Europe (except for an instance of 27% in Switzerland's Upper Rhone Valley) in contrast to the prominent spread of derived M412 varieties in West Europe (Figure 1f).

Major R1b Founder Effect in West Europe

R1b-M412 appears to be the most common Y-chromosome haplogroup in Western Europe (>70%), while being virtually absent in the Near East, the Caucasus and West Asia (Figure 1f). Recent founder effects could explain why the M412-L11 assemblage of chromosomes is abundant and restricted to Western parts of Europe (Figure 1f and g).

Examples of additional founder effects and subsequent demographic expansions are evident among the more prominent L11-related, S116 (Figure 1i) and U106 (Figure 1k) components that generally distribute West and East of the Rhine river basin, respectively. Within the three major sub-haplogroups of the S116 assemblage further geographic localization is evident. Specifically, S116*(xU152, M529) occurrence is maximal in Iberia (Figure 1j), whereas the U152 branch is most frequent (20–44%) in Switzerland, Italy, France and Western Poland, with additional instances exceeding 15% in some regions of England and Germany (Figure 1l). Last, the M529 clade is highest (25–50%) in England and Ireland (Figure 1m and n), with the M222 sub-clade (Figure 1o) mainly restricted to Ireland.

Principal component analysis by haplogroup R1b sub-clades: (a) M269*, L23, M412*, L11*, U106, S116*, U152 and M529 sub-haplogroups with respect to total M269, and (b) by collapsing the 118 populations into 34 regionally defined populations. We excluded populations when the total R1b frequency was <5% or the count was less than n=5. Population codes: Austria (AUT); Belarus (BLR); Crete (CRE); Croatia (CRO); Czech Republic (CZE); Denmark (DNK); England (ENG); Estonia (EST); France (FRA); Germany (GER); Greece (GRC); Hungary (HUN); Ireland (IRL); Italy (ITA); Komis from Perm Oblast, Russia (KOM); Kosovo (KOS); Northeast Caucasus (NEC); Netherlands (NLD); Poland (POL); Portugal (PRT); Romania (ROM); Russians from Russia (RUS); Serbia (SER); Southern Bashkirs from Bashkortostan, Russia (SB); Southeastern Bashkirs from Bashkortostan, Russia (SEB); Southwestern Bashkirs from Bashkortostan, Russia (SWB); Slovakia (SVK); Slovenia (SVN); South Sweden (SSW); Spain (ESP); Switzerland (SWI); Tatars from Russia (TAT); Turkey (TUR); Ukraine (UKR).

The initial arrival of farmers from Southwest Asia to the present-day Greece occurred ca 9000 years BP.38 Outside of Southeast Europe, two episodes of early farming are attested archeologically.39 The first involved a maritime colonization of Crete ca 9000 years BP and Southern Italy ca 8000 years BP and subsequently spread to coastal Mediterranean France and Spain, as exemplified by impressed/cardial pottery. The second involved a migration to Central Europe, from Hungary to France, characterized by LBK (ca 7500 years BP). Within a 3k-year period, the agricultural economy spread across Europe, terminating in Britain and Scandinavia ~6000 years BP.39

This study has evaluated the spatial and temporal distributions of sub-clades of Y-chromosome haplogroup R1b-M269 in Europe, the Near East, the Circum-Uralic region and the Caucasus, revealing the major M412-defined phylogenetic dichotomy between the Central/Western Europe and more easterly distributed representatives (Figure 1e and f, respectively). In addition, several additional sub-haplogroup varieties, especially those in Central and Western Europe, display patterns with geographic locality (Figure 1g–o) and clinality (Supplementary Figure 1). The enhanced resolution of M412-related lineages permits a finer-grained view of the proposal that R1b-M269 coincides with the arrival and spread of farming into Europe. A recent analysis of 9 Y-STR loci associated with 840 R1b chromosomes resolved just to the level of M269 concluded that all such chromosomes in Europe reflect a recent genetic heritage that was uniformly introduced by exogenous farmers migrating from Western Anatolia.23 Our high-resolution SNP genotype results show that the majority of Central and Western European haplogroups relate to common M412 founders whose sub-clades display phylogeographic and temporal patterns consistent with allele surfing at the periphery of expansions.40, 41 Opportunities for the establishment of new varieties on a regional basis would be enhanced if preexisting population densities were not excessive. Estimates of population densities in the early Neolithic suggest that they were low, 0.6 per square kilometer.42 Such low population densities would have helped to promote founder effects such as those seen for the more prominent L11-related, S116 (Figure 1j) and U106 (Figure 1i) components and their respective sub-haplogroups. This is shown in part as the inversely related decreasing expansion times of S116-related haplogroups with increased distance from high-diversity areas coincident with the establishment of the early Danubian Neolithic LBK horizon in Europe (Figure 2a and b).

Our results implicate complexity in the post-glacial formation and expansion of populations in Europe during the past ca 10 000 years. The narrow temporal window between potential expansions by Mesolithic foragers at the onset of the Holocene (10k years ago) and pioneer farmers from the Near East during the early Neolithic into Central Europe (7.5k years ago) is exceedingly difficult to discern with genetic tools.22 Thus, invoking the pronounced transformation of the pre-Neolithic European gene pool by intrusive pioneer farmers from the Near East must be viewed cautiously especially when such an argument is based on just a single incompletely resolved haplogroup. Although the transition to agriculture was a pivotal event in human history, the spread of specific haplogroups can occur in more than one migration event. Evidence of trade networks based on the exchange of commodities (eg salt, amber) along northwest to south and southeast directions, eg the Iron Age Hallstatt Culture,43 provided opportunities for potential gene dispersion. However, the magnitude of such putative commodity-driven gene flows remains uncertain until direct evidence from ancient DNA is provided in combination with potentially even more high-resolution and informative sub-haplogroup fractions relevant to particular trade routes or cultural horizons are detected and used to test hypotheses concerning post-Neolithic histories.

Myres, Natalie M., et al. "A major Y-chromosome haplogroup R1b Holocene era founder effect in Central and Western Europe." European Journal of Human Genetics 19.1 (2010): 95-101.

Last Edit: Jan 2, 2019 22:01:31 GMT by Admin