Ancient DNA still makes changes
While it has been 50,000 years since the last Human-Neanderthal mating, we may still be haunted by our ancient predecessors.
Neanderthal DNA still exists, in bits and pieces, within the modern human genome.
Researchers have been uncertain about the impact of Neanderthals' genetic contribution but they have now found evidence that Neanderthal DNA sequences still influence how genes are turned on or off in modern humans.
Neanderthal genes can change gene expression, and likely contribute to traits such as height and susceptibility to schizophrenia or lupus, University of Washington researchers found.
“Even 50,000 years after the last human-Neanderthal mating, we can still see measurable impacts on gene expression,” says geneticist and study co-author Joshua Akey.
“And those variations in gene expression contribute to human phenotypic variation and disease susceptibility.”
Previous studies have found correlations between Neanderthal genes and traits such as fat metabolism, depression, and lupus risk. However, figuring out the mechanism behind the correlations has proved difficult.
In this study, researchers analysed RNA sequences to find people who carry both Neanderthal and modern human versions of any given gene - one version from each parent.
For each such gene, the investigators then compared expression of the two alleles head-to-head in 52 different tissues.
“We find that for about 25 per cent of all those sites that we tested, we can detect a difference in expression between the Neanderthal allele and the modern human allele,” says the study's first author, UW postdoctoral researcher Rajiv McCoy.
Expression of Neanderthal alleles tended to be especially low in the brain and the testes, suggesting that those tissues may have experienced more rapid evolution since we diverged from Neanderthals approximately 700,000 years ago.
“We can infer that maybe the greatest differences in gene regulation exist in the brain and testes between modern humans and Neanderthals,” says Akey.
One example uncovered by the study is a Neanderthal allele of a gene called ADAMTSL3 that decreases risk of schizophrenia, while also influencing height.
When the Neanderthal mutation is present, the cell's machinery removes a segment of the mRNA that is expressed in the modern human version. The cell ends up making a modified protein because of a single mutation from a Neanderthal ancestor.
The connection between that modified protein, height, and schizophrenia still requires more investigation, but it is an example of how small differences between modern humans and Neanderthals can contribute to variation in people.
“Hybridisation between modern humans and Neanderthals increased genomic complexity,” explains Akey.
“Hybridisation wasn't just something that happened 50,000 years ago that we don't have to worry about anymore. Those little bits and pieces, our Neanderthal relics, are influencing gene expression in pervasive and important ways.”
Next steps may include investigating whether Denisovans - another species of hominins that crossbred with modern humans - are contributing to gene expression.