Humans whose genetic ancestors lived outside Africa have a small proportion of the genome that traces back to interbreeding events with Neanderthals. To quantify the contribution of this ancestry to present-day phenotypic variation, scientists from Cornell University and elsewhere developed a convincing set of approaches that takes into account various complicating factors and applied it to about 300,000 unrelated white British individuals in the UK Biobank.
Wei et al. developed rigorous methods to assess the contribution of introgressed Neanderthal variants to heritable trait variation and applied these methods to analyze 235,592 introgressed Neanderthal variants and 96 distinct phenotypes measured in about 300,000 unrelated white British individuals in the UK Biobank. Image credit: Neanderthal Museum.
“Interestingly, we found that several of the identified genes involved in modern human immune, metabolic and developmental systems might have influenced human evolution after the ancestors’ migration out of Africa,” said Cornell University’s Dr. April (Xinzhu) Wei, lead author of the study.
“We have made our custom software available for free download and use by anyone interested in further research.”
Using a vast dataset from the UK Biobank consisting of genetic and trait information of nearly 300,000 Brits of non-African ancestry, the researchers analyzed more than 235,000 genetic variants likely to have originated from Neanderthals.
They found that 4,303 of those differences in DNA are playing a substantial role in modern humans and influencing 47 distinct genetic traits, such as how fast someone can burn calories or a person’s natural immune resistance to certain diseases.
Unlike previous studies that could not fully exclude genes from modern human variants, the new study leveraged more precise statistical methods to focus on the variants attributable to Neanderthal genes.
While the authors used a dataset of almost exclusively white individuals living in the United Kingdom, their computational methods could offer a path forward in gleaning evolutionary insights from other large databases to delve deeper into archaic humans’ genetic influences on modern humans.
“For scientists studying human evolution interested in understanding how interbreeding with archaic humans tens of thousands of years ago still shapes the biology of many present-day humans, this study can fill in some of those blanks,” said senior author Dr. Sriram Sankararaman, a researcher at the University of California, Los Angeles.
“More broadly, our findings can also provide new insights for evolutionary biologists looking at how the echoes of these types of events may have both beneficial and detrimental consequences.”
The study was published online in the journal eLife.
_____
Xinzhu Wei et al. The lingering effects of Neanderthal introgression on human complex traits. eLife, published online March 20, 2023; doi: 10.7554/eLife.80757
