Research Article

Insights into human genetic variation and population history from 929 diverse genomes

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Science  20 Mar 2020:
Vol. 367, Issue 6484, eaay5012
DOI: 10.1126/science.aay5012

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Genomes from around the globe

Genomic sequencing of diverse human populations to understand overall genetic diversity has lagged behind in-depth examination of specific populations. To add to our understanding of human genetic diversity, Bergström et al. generated whole-genome sequences surveying individuals in the Human Genome Diversity Project, which is a panel of global populations that has been instrumental in understanding the history of human populations. The authors' study adds data about African, Oceanian, and Amerindian populations and indicates that diversity tends to result from differences at the single-nucleotide level rather than copy number variation. An analysis of archaic sequences in modern populations identifies ancestral genetic variation in African populations that likely predates modern humans and has been lost in most non-African populations.

Science, this issue p. eaay5012

Structured Abstract

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.

Structure of genetic variation across worldwide human populations.

Shown is a schematic illustration of the approximate amounts of four different classes of genetic variation found in different geographical regions. The origins of the populations included in the study are indicated by dots.

Abstract

Genome sequences from diverse human groups are needed to understand the structure of genetic variation in our species and the history of, and relationships between, different populations. We present 929 high-coverage genome sequences from 54 diverse human populations, 26 of which are physically phased using linked-read sequencing. Analyses of these genomes reveal an excess of previously undocumented common genetic variation private to southern Africa, central Africa, Oceania, and the Americas, but an absence of such variants fixed between major geographical regions. We also find deep and gradual population separations within Africa, contrasting population size histories between hunter-gatherer and agriculturalist groups in the past 10,000 years, and a contrast between single Neanderthal but multiple Denisovan source populations contributing to present-day human populations.

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