The distinct morphological phenotypes of Southeast Asian aborigines are shaped by novel mechanisms for adaptation to tropical rainforests.

Southeast Asian aborigines, the hunter-gatherer populations living in tropical rainforests, exhibit distinct morphological phenotypes, including short stature, dark skin, curly hair and a wide and snub nose. The underlying genetic architecture and evolutionary mechanism of these phenotypes remain a long-term mystery. We conducted whole genome deep sequencing of 81 Cambodian aborigines from eight ethnic groups. Through a genome-wide scan of selective sweeps, we discovered key genes harboring Cambodian-enriched mutations that may contribute to their phenotypes, including two hair morphogenesis genes (TCHH and TCHHL1), one nasal morphology gene (PAX3) and a set of genes (such as ENTPD1-AS1) associated with short stature. The identified new genes and novel mutations suggest an independent origin of the distinct phenotypes in Cambodian aborigines through parallel evolution, refuting the long-standing argument on the common ancestry of these phenotypes among the worldwide rainforest hunter-gatherers. Notably, our discovery reveals that various types of molecular mechanisms, including antisense transcription and epigenetic regulation, contribute to human morphogenesis, providing novel insights into the genetics of human environmental adaptation.

A Genetic Mechanism for Convergent Skin Lightening during Recent Human Evolution.

Skin lightening among Eurasians is thought to have been a convergence occurring independently in Europe and East Asia as an adaptation to high latitude environments. Among Europeans, several genes responsible for such lightening have been found, but the information available for East Asians is much more limited. Here, a genome-wide comparison between dark-skinned Africans and Austro-Asiatic speaking aborigines and light-skinned northern Han Chinese identified the pigmentation gene OCA2, showing unusually deep allelic divergence between these groups. An amino acid substitution (His615Arg) of OCA2 prevalent in most East Asian populations-but absent in Africans and Europeans-was significantly associated with skin lightening among northern Han Chinese. Further transgenic and targeted gene modification analyses of zebrafish and mouse both exhibited the phenotypic effect of the OCA2 variant manifesting decreased melanin production. These results indicate that OCA2 plays an important role in the convergent skin lightening of East Asians during recent human evolution.

Y-chromosome diversity suggests southern origin and Paleolithic backwave migration of Austro-Asiatic speakers from eastern Asia to the Indian subcontinent.

Analyses of an Asian-specific Y-chromosome lineage (O2a1-M95)--the dominant paternal lineage in Austro-Asiatic (AA) speaking populations, who are found on both sides of the Bay of Bengal--led to two competing hypothesis of this group's geographic origin and migratory routes. One hypothesis posits the origin of the AA speakers in India and an eastward dispersal to Southeast Asia, while the other places an origin in Southeast Asia with westward dispersal to India. Here, we collected samples of AA-speaking populations from mainland Southeast Asia (MSEA) and southern China, and genotyped 16 Y-STRs of 343 males who belong to the O2a1-M95 lineage. Combining our samples with previous data, we analyzed both the Y-chromosome and mtDNA diversities. We generated a comprehensive picture of the O2a1-M95 lineage in Asia. We demonstrated that the O2a1-M95 lineage originated in the southern East Asia among the Daic-speaking populations ~20-40 thousand years ago and then dispersed southward to Southeast Asia after the Last Glacial Maximum before moving westward to the Indian subcontinent. This migration resulted in the current distribution of this Y-chromosome lineage in the AA-speaking populations. Further analysis of mtDNA diversity showed a different pattern, supporting a previously proposed sex-biased admixture of the AA-speaking populations in India.

An updated phylogeny of the human Y-chromosome lineage O2a-M95 with novel SNPs.

Though the Y-chromosome O2a-M95 lineage is one of the major haplogroups present in eastern Asian populations, especially among Austro-Asiatic speaking populations from Southwestern China and mainland Southeast Asia, to date its phylogeny lacks structure due to only one downstream SNP marker (M88) assigned to the lineage. A recent array-capture-based Y chromosome sequencing of Asian samples has yielded a variety of novel SNPs purportedly belonging to the O2a-M95 lineage, but their phylogenetic positions have yet to be determined. In this study, we sampled 646 unrelated males from 22 Austro-Asiatic speaking populations from Cambodia, Thailand and Southwestern China, and genotyped 12 SNP makers among the sampled populations, including 10 of the newly reported markers. Among the 646 males, 343 belonged to the O2a-M95 lineage, confirming the supposed dominance of this Y chromosome lineage in Austro-Asiatic speaking populations. We further characterized the phylogeny of O2a-M95 by defining 5 sub-branches: O2a1*-M95, O2a1a-F789, O2a1b*-F1252, O2a1b1*-M88 and O2a1b1a -F761. This updated phylogeny not only improves the resolution of this lineage, but also allows for greater tracing of the prehistory of human populations in eastern Asia and the Pacific, which may yield novel insights into the patterns of language diversification and population movement in these regions.

Analysis of mitochondrial genome diversity identifies new and ancient maternal lineages in Cambodian aborigines.

Cambodia harbours a variety of aboriginal (and presumably ancient) populations that have largely been ignored in studies of genetic diversity. Here we investigate the matrilineal gene pool of 1,054 Cambodians from 14 geographic populations. Using mitochondrial whole-genome sequencing, we identify eight new mitochondrial DNA haplogroups, all of which are either newly defined basal haplogroups or basal sub-branches. Most of the new basal haplogroups have very old coalescence ages, ranging from ~55,000 to ~68,000 years, suggesting that present-day Cambodian aborigines still carry ancient genetic polymorphisms in their maternal lineages, and most of the common Cambodian haplogroups probably originated locally before expanding to the surrounding areas during prehistory. Moreover, we observe a relatively close relationship between Cambodians and populations from the Indian subcontinent, supporting the earliest costal route of migration of modern humans from Africa into mainland Southeast Asia by way of the Indian subcontinent some 60,000 years ago.