No abstract

It has recently been shown that ancestors of New Guineans and Bougainville Islanders have inherited a proportion of their ancestry from Denisovans, an archaic hominin group from Siberia. However, only a sparse sampling of populations from Southeast Asia and Oceania were analyzed. Here, we quantify Denisova admixture in 33 additional populations from Asia and Oceania. Aboriginal Australians, Near Oceanians, Polynesians, Fijians, east Indonesians, and Mamanwa (a "Negrito" group from the Philippines) have all inherited genetic material from Denisovans, but mainland East Asians, western Indonesians, Jehai (a Negrito group from Malaysia), and Onge (a Negrito group from the Andaman Islands) have not. These results indicate that Denisova gene flow occurred into the common ancestors of New Guineans, Australians, and Mamanwa but not into the ancestors of the Jehai and Onge and suggest that relatives of present-day East Asians were not in Southeast Asia when the Denisova gene flow occurred. Our finding that descendants of the earliest inhabitants of Southeast Asia do not all harbor Denisova admixture is inconsistent with a history in which the Denisova interbreeding occurred in mainland Asia and then spread over Southeast Asia, leading to all its earliest modern human inhabitants. Instead, the data can be most parsimoniously explained if the Denisova gene flow occurred in Southeast Asia itself. Thus, archaic Denisovans must have lived over an extraordinarily broad geographic and ecological range, from Siberia to tropical Asia.

We describe a PCA-based genome scan approach to analyze genome-wide admixture structure, and introduce wavelet transform analysis as a method for estimating the time of admixture. We test the wavelet transform method with simulations and apply it to genome-wide SNP data from eight admixed human populations. The wavelet transform method offers better resolution than existing methods for dating admixture, and can be applied to either SNP or sequence data from humans or other species.

BackgroundGenome-wide scans of hundreds of thousands of single-nucleotide polymorphisms (SNPs) have resulted in the identification of new susceptibility variants to common diseases and are providing new insights into the genetic structure and relationships of human populations. Moreover, genome-wide data can be used to search for signals of recent positive selection, thereby providing new insights into the genetic adaptations that occurred as modern humans spread out of Africa and around the world.MethodologyWe genotyped approximately 500,000 SNPs in 255 individuals (5 individuals from each of 51 worldwide populations) from the Human Genome Diversity Panel (HGDP-CEPH). When merged with non-overlapping SNPs typed previously in 250 of these same individuals, the resulting data consist of over 950,000 SNPs. We then analyzed the genetic relationships and ancestry of individuals without assigning them to populations, and we also identified candidate regions of recent positive selection at both the population and regional (continental) level.ConclusionsOur analyses both confirm and extend previous studies; in particular, we highlight the impact of various dispersals, and the role of substructure in Africa, on human genetic diversity. We also identified several novel candidate regions for recent positive selection, and a gene ontology (GO) analysis identified several GO groups that were significantly enriched for such candidate genes, including immunity and defense related genes, sensory perception genes, membrane proteins, signal receptors, lipid binding/metabolism genes, and genes involved in the nervous system. Among the novel candidate genes identified are two genes involved in the thyroid hormone pathway that show signals of selection in African Pygmies that may be related to their short stature.

Genome-wide scans for positive selection in humans provide a promising approach to establish links between genetic variants and adaptive phenotypes. From this approach, lists of hundreds of candidate genomic regions for positive selection have been assembled. These candidate regions are expected to contain variants that contribute to adaptive phenotypes, but few of these regions have been associated with phenotypic effects. Here we present evidence that a derived nonsynonymous substitution (370A) in EDAR, a gene involved in ectodermal development, was driven to high frequency in East Asia by positive selection prior to 10,000 years ago. With an in vitro transfection assay, we demonstrate that 370A enhances NF-κB activity. Our results suggest that 370A is a positively selected functional genetic variant that underlies an adaptive human phenotype.

The Australian continent holds some of the earliest archaeological evidence for the expansion of modern humans out of Africa, with initial occupation at least 40,000 y ago. It is commonly assumed that Australia remained largely isolated following initial colonization, but the genetic history of Australians has not been explored in detail to address this issue. Here, we analyze large-scale genotyping data from aboriginal Australians, New Guineans, island Southeast Asians and Indians. We find an ancient association between Australia, New Guinea, and the Mamanwa (a Negrito group from the Philippines), with divergence times for these groups estimated at 36,000 y ago, and supporting the view that these populations represent the descendants of an early “southern route” migration out of Africa, whereas other populations in the region arrived later by a separate dispersal. We also detect a signal indicative of substantial gene flow between the Indian populations and Australia well before European contact, contrary to the prevailing view that there was no contact between Australia and the rest of the world. We estimate this gene flow to have occurred during the Holocene, 4,230 y ago. This is also approximately when changes in tool technology, food processing, and the dingo appear in the Australian archaeological record, suggesting that these may be related to the migration from India.

Although the Austronesian expansion had a major impact on the languages of Island Southeast Asia, controversy still exists over the genetic impact of this expansion. The coexistence of both Asian and Papuan genetic ancestry in Eastern Indonesia provides a unique opportunity to address this issue. Here, we estimate recombination breakpoints in admixed genomes based on genome-wide SNP data and date the genetic admixture between populations of Asian vs. Papuan ancestry in Eastern Indonesia. Analyses of two genome-wide datasets indicate an eastward progression of the Asian admixture signal in Eastern Indonesia beginning about 4,000–3,000 y ago, which is in excellent agreement with inferences based on Austronesian languages. The average rate of spread of Asian genes in Eastern Indonesia was about 0.9 km/y. Our results indicate that the Austronesian expansion had a strong genetic as well as linguistic impact on Island Southeast Asia, and they significantly advance our understanding of the biological origins of human populations in the Asia–Pacific region.

Studies of Native South American genetic diversity have helped to shed light on the peopling and differentiation of the continent, but available data are sparse for the major ecogeographic domains. These include the Pacific Coast, a potential early migration route; the Andes, home to the most expansive complex societies and to one of the most widely spoken indigenous language families of the continent (Quechua); and Amazonia, with its understudied population structure and rich cultural diversity. Here, we explore the genetic structure of 176 individuals from these three domains, genotyped with the Affymetrix Human Origins array. We infer multiple sources of ancestry within the Native American ancestry component; one with clear predominance on the Coast and in the Andes, and at least two distinct substrates in neighboring Amazonia, including a previously undetected ancestry characteristic of northern Ecuador and Colombia. Amazonian populations are also involved in recent gene-flow with each other and across ecogeographic domains, which does not accord with the traditional view of small, isolated groups. Long-distance genetic connections between speakers of the same language family suggest that indigenous languages here were spread not by cultural contact alone. Finally, Native American populations admixed with post-Columbian European and African sources at different times, with few cases of prolonged isolation. With our results we emphasize the importance of including understudied regions of the continent in high-resolution genetic studies, and we illustrate the potential of SNP chip arrays for informative regional-scale analysis.