Global human genome study reveals our complex evolutionary history

Uncovering a large amount of previously undescribed genetic variation, the study provides new insights into our evolutionary past, and highlights the complexity of the process through which our ancestors diversified, migrated and mixed throughout the world.

Published in the journal Science, the work involved the University of Cambridge, the Wellcome Sanger Institute, the Francis Crick Institute and other collaborators. It is the first to apply the latest high-quality sequencing technology to such a large and diverse set of humans, covering 929 genomes from 54 geographically, linguistically and culturally diverse populations from across the globe. 

The results provide unprecedented detail of our genetic history, and highlights how it is characterised by multiple layers of complexity. Although genetic differences between populations reflect their diversity, many patterns are shared across continents, revealing both ancient and recent connections between populations.

Researchers in the University of Cambridge’s Department of Genetics analysed the sequencing data to investigate evidence of interbreeding between the ancestors of modern humans and extinct human lineages such as Neanderthals and Denisovans, which occurred 40,000 to 60,000 years ago. 

They found evidence that the Neanderthal ancestry of modern humans can be explained by just one major ‘mixing event’, most likely involving several Neanderthal individuals coming into contact with modern humans shortly after the latter had expanded out of Africa. 

"Studying the patterns of Neanderthal ancestry in present-day humans hints at the structure of human communities more than 50,000 years ago. It is remarkable that patterns of Neanderthal ancestry are so similar in populations around the world today, and may have derived from a single Neanderthal population," said Dr Aylwyn Scally, a researcher in the University of Cambridge’s Department of Genetics who was involved in the study.

In contrast, several different sets of DNA segments inherited from Denisovans were identified in people from Oceania and East Asia, suggesting at least two distinct mixing events. “This could suggest that multiple small groups of Denisovans once lived in different regions of Asia. We expect future discoveries of ancient DNA - perhaps from other extinct humans and perhaps even inside Africa - to tell us more about ancient population structure and diversity," said Dr Ruoyun Hui at the University of Cambridge’s Department of Genetics, who also worked on the study.

Until recently, it was thought that only people outside sub-Saharan Africa had Neanderthal DNA. Now, the discovery of small amounts of Neanderthal DNA in west African people is most likely to reflect genetic backflow into Africa from Eurasia. 

The consensus view of human history is that the ancestors of present-day humans diverged from the ancestors of extinct Neanderthal and Denisovan groups around 500,000-700,000 years ago, before the emergence of ‘modern’ humans in Africa in the last few hundred thousand years.

Around 50,000-70,000 years ago, some humans expanded out of Africa and soon after mixed with archaic Eurasian groups. After that, populations grew rapidly, with extensive migration and mixture as many groups transitioned from hunter-gatherers to food producers over the last 10,000 years.

The new data is freely available worldwide to benefit the study of human evolution and genetic diversity, including studies of genetic susceptibility to disease in different parts of the world.

The team found millions of previously unknown DNA variations that are exclusive to one continental or major geographical region. Though most of these were rare, they included common variations in certain African and Oceanian populations that had not been identified by previous studies – variations that may influence the susceptibility of different populations to disease. 

Medical genetics studies have so far predominantly been conducted in populations of European ancestry, meaning that any medical implications that these variants might have are not known. Identifying these novel variants represents a first step towards fully expanding the study of genomics to underrepresented populations.

However, no single DNA variation was found to be present in 100 per cent of genomes from any major geographical region while being absent from all other regions. This finding underlines that the majority of common genetic variation is found across the globe.

“The detail provided by this study allows us to look deeper into human history, particularly inside Africa where less is currently known about the timescale of human evolution,” said Dr Anders Bergström, of the Francis Crick Institute and formerly the Wellcome Sanger Institute. “We find that the ancestors of present-day populations diversified through a gradual and complex process mostly during the last 250,000 years, with large amounts of gene flow between these early lineages. But we also see evidence that small parts of human ancestries trace back to groups that diversified much earlier than this.”

This study was funded by Wellcome and the Francis Crick Institute.

Reference
Bergström, A. et al. Insights into human genetic variation and population history from 929 diverse genomes, Science, March 2020; DOI: 10.1126/science.aay5012

Adapted from a press release by The Wellcome Sanger Institute.