High Res Modern DNA Sheds Light On Archaic Admixture

New high precision whole genomes from a diverse global sample is removing Eurocentric biases of earlier lower precision studies. One thing that this does is reveal more relatively young and less widespread mutations that can shed light on the relationships and admixture histories of modern human populations.

This has also shed light on modern human admixture with archaic hominins including Neanderthals and Denisovans. Neanderthal admixture either happened early with a small number of individuals, or homogeneous group of individuals, or both. Denisovan admixture, in contrast, shows signs of multiple admixture events with regionally distinct genetic populations of Denisovans.

[T]he new high-quality whole-genome analysis of the HGDP dataset is finally published in Science, Insights into human genetic variation and population history from 929 diverse genomes. The HGDP dates back 30 years, so this is the culmination of a long line of research. The authors in this paper looked at nearly 1,000 HGDP individuals at high coverage sequencing, meaning that they had extremely good confidence in their calls of the state of a base across all 3 billion pairs. 

This is in contrast to the ~600,000 markers in the original HGDP analyses from the 2000s, which came from results of a “SNP-array.” A SNP-array of this form focuses on the variation by looking at polymorphic sites (sites which vary in the population). How did they originally determine what was polymorphic? Unfortunately, they had to rely on European populations, so the original analyses were using a quite skewed measuring stick. . . .

The Neanderthals who mixed into early humans were quite homogeneous, or, there were not many of them. The haplotypes are not too numerous, and, they don’t exhibit the patterns you’d expect from different admixtures and source populations. The diversity is too great to be a single individual, but it could have been a small number. The main caution I would suggest here is that Neanderthals seem to often be quite homogeneous on the local scale. 

The Denisovans are a different story. They detect the difference between Oceanian and non-Oceanian Denisovan ancestry (the Oceanian source Denisovans were quite distinct from the Altai Denisovans). But they also detect a different Denisovan contribution to the genomes of the Cambodians. The indigenous people of the Philippines also harbor different Denisovan ancestry (not in this paper). The “Denisovans” seem to have been a cluster of different lineages that persisted in parallel for a long time.

From Razib Khan. 

The abstract of the new paper is as follows:

INTRODUCTION 

Large-scale human genome-sequencing studies to date have been limited to large, metropolitan populations or to small numbers of genomes from each group. Much remains to be understood about the extent and structure of genetic variation in our species and how it was shaped by past population separations, admixture, adaptation, size changes, and gene flow from archaic human groups. Larger numbers of genome sequences from more diverse populations are needed to answer these questions. 

RATIONALE 

We sequenced 929 genomes from 54 geographically, linguistically, and culturally diverse human populations to an average of 35× coverage and analyzed the variation among them. We also physically resolved the haplotype phase of 26 of these genomes using linked-read sequencing. 

RESULTS 

We identified 67.3 million single-nucleotide polymorphisms, 8.8 million small insertions or deletions (indels), and 40,736 copy number variants. This includes hundreds of thousands of variants that had not been discovered by previous sequencing efforts, but which are common in one or more population. We demonstrate benefits to the study of population relationships of genome sequences over ascertained array genotypes, particularly when involving African populations. 

Populations in central and southern Africa, the Americas, and Oceania each harbor tens to hundreds of thousands of private, common genetic variants. Most of these variants arose as new mutations rather than through archaic introgression, except in Oceanian populations, where many private variants derive from Denisovan admixture. Although some reach high frequencies, no variants are fixed between major geographical regions.

We estimate that the genetic separation between present-day human populations occurred mostly within the past 250,000 years. However, these early separations were gradual in nature and shaped by protracted gene flow. All populations thus still had some genetic contact more recently than this, but there is also evidence that a small fraction of present-day structure might be hundreds of thousands of years older. Most populations expanded in size over the past 10,000 years, but hunter-gatherer groups did not.

The low diversity among the Neanderthal haplotypes segregating in present-day populations indicates that, while more than one Neanderthal individual must have contributed genetic material to modern humans, there was likely only one major episode of admixture. By contrast, Denisovan haplotype diversity reflects a more complex history involving more than one episode of admixture.

We found small amounts of Neanderthal ancestry in West African genomes, most likely reflecting Eurasian admixture. Despite their very low levels or absence of archaic ancestry, African populations share many Neanderthal and Denisovan variants that are absent from Eurasia, reflecting how a larger proportion of the ancestral human variation has been maintained in Africa.

CONCLUSION 

The discovery of substantial amounts of common genetic variation that was previously undocumented and is geographically restricted highlights the continued value of anthropologically informed study designs for understanding human diversity. The genome sequences presented here are a freely available resource with relevance to population history, medical genetics, anthropology, and linguistics.