Approximately 6% of the Altai Neanderthal genome was inherited from an ancient lineage of anatomically modern Homo sapiens that migrated from Africa to Eurasia over 250,000 years ago, according to new research led by the University of Pennsylvania.
Comparisons of Neanderthal genomes to anatomically modern human (AMH) genomes show a history of Neanderthal-to-AMH introgression stemming from interbreeding after the migration of AMHs from Africa to Eurasia. All non-sub-Saharan African AMHs have genomic regions genetically similar to Neanderthals that descend from this introgression. Regions of the genome with Neanderthal similarities have also been identified in sub-Saharan African populations, but their origins have been unclear. To better understand how these regions are distributed across sub-Saharan Africa, the source of their origin, and what their distribution within the genome tells us about early AMH and Neanderthal evolution, Harris et al. analyzed a dataset of high-coverage, whole-genome sequences from 180 individuals from 12 diverse sub-Saharan African populations. Image credit: Holger Neumann / Neanderthal Museum.
“We found this reflection of ancient interbreeding where genes flowed from ancient modern humans into Neanderthals,” said co-first author Dr. Alexander Platt, a researcher in the Department of Genetics at the University of Pennsylvania.
“This group of individuals left Africa between 250,000 and 270,000 years ago. They were sort of the cousins to all humans alive today, and they were much more like us than Neanderthals.”
“We arrived at this conclusion by comparing a Neanderthal genome with a diverse set of genomes from modern indigenous populations in sub-Saharan Africa.”
“Our study highlights the importance of including ethnically and geographically diverse populations in human genetics and genomic studies,” said University of Pennsylvania’s Professor Sarah Tishkoff, senior author of the study.
To better understand how widespread Neanderthal-like DNA regions are across sub-Saharan Africa and to elucidate their origins, the researchers analyzed the genomes of 180 individuals from 12 different populations in Cameroon, Botswana, Tanzania, and Ethiopia.
For each genome, they identified regions of Neanderthal-like DNA and looked for evidence of Neanderthal ancestry.
Then, they compared the modern human genomes to a genome belonging to a Neanderthal who lived in the Altai Mountains, Siberia, approximately 120,000 years ago.
For this comparison, the researchers developed a novel statistical method that allowed them to determine the origins of the Neanderthal-like DNA in these modern sub-Saharan populations, whether they were regions that Neanderthals inherited from modern humans or regions that modern humans inherited from Neanderthals and then brought back to Africa.
They found that all of the sub-Saharan populations contained Neanderthal-like DNA, indicating that this phenomenon is widespread.
In most cases, this Neanderthal-like DNA originated from an ancient lineage of modern humans that passed their DNA on to Neanderthals when they migrated from Africa to Eurasia around 250,000 years ago.
As a result of this modern human-Neanderthal interbreeding, approximately 6% of the Neanderthal genome was inherited from modern humans.
In some specific sub-Saharan populations, the researchers also found evidence of Neanderthal ancestry that was introduced to these populations when humans bearing Neanderthal genes migrated back into Africa.
Neanderthal ancestry in these sub-Saharan populations ranged from 0 to 1.5%, and the highest levels were observed in the Amhara from Ethiopia and Fulani from Cameroon.
To try to understand whether carrying modern human DNA was helpful or harmful when introduced into the Neanderthal genome, the scientists also investigated where these chunks of modern human DNA were located.
They found that most of the modern human DNA was in non-coding regions of the Neanderthal genome, indicating that modern human gene variants were being preferentially lost from coding sections of the genome, which suggests that having modern human genes in a Neanderthal background is detrimental to fitness.
This is similar to what is seen in modern humans, where natural selection has slowly been removing Neanderthal genes from modern human populations.
“So a Neanderthal allele might work great in Neanderthals, but you plop it into a modern human genome and it causes problems,” Dr. Platt said.
“Both modern humans and Neanderthals slowly rid themselves of the alleles of the other group.”
“In the almost 500,000 years between the ancestors of Neanderthals splitting off from the ancestors of modern humans and these other modern humans being reintroduced to Neanderthal populations, we had become such different organisms that, although we were still able to interbreed quite readily, the hybrids didn’t work so well, which means we were very far along the path to becoming distinct species.”
The research opens new avenues for exploring human evolution by identifying a genetic reference of a population that occupies a part of the human family tree that had previously been lacking from the genomic and fossil record.
“Discovering this ancient lineage of modern humans is really exciting for future research because it gives us a different lens to look at human evolution,” said co-first author Dr. Daniel Harris, a postdoctoral researcher in the Department of Genetics at the University of Pennsylvania.
“Because we don’t have DNA sequences from modern human fossils from that long ago, identifying these sequences will shed light on very early modern human evolution in Africa.”
The findings were published in the journal Current Biology.
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Daniel N. Harris et al. Diverse African genomes reveal selection on ancient modern human introgressions in Neanderthals. Current Biology, published online October 13, 2023; doi: 10.1016/j.cub.2023.09.066
