Part of the genetic heritage of modern humans comes from mixing with Denisovans tens of thousands of years ago – and subsequent genetic adaptations may have predisposed us to certain mental health problems, such as depression.
That’s the conclusion of a new study by researchers in Spain, who followed up on previous research that highlighted a variant of the gene SLC30A9 as likely to have evolved through positive selection, particularly in East Asian populations.
The gene is responsible for regulating zinc and its transport across cell membranes. Zinc is important for healthy growth and the proper functioning of our neurological and immune systems, and this particular adaptation tweaks that regulation.
So where does this genetic adaptation come from? A close comparison with the Denisovan genome revealed a match for the same mutation identified in East Asia, although there was no such match with Neanderthal populations.
“Through genomic analysis, we found that the observed genetic variant came from our past interbreeding with archaic humans, possibly the Denisovans,” says evolutionary biologist Ana Roca-Umbert of the UPF.
Laboratory experiments carried out by the team showed that this variation is associated with differences in the way some cellular structures – including the ‘powerhouses’ of the mitochondria – handle zinc, which may influence its effect on metabolism.
Researchers have also suggested that evolution has favoured the retention of SLC30A9 for some reason, but have never been able to work out exactly what benefits it might provide. It’s now possible that the Denisovan variant gave us better protection against cold climates.
“Apparently, the change was beneficial and turned out to be a selective advantage for humans,” says UPF evolutionary biologist Jorge Garcia-Calleja.
“As a result, this variation in the SLC30A9 gene was selected and has reached today’s populations”.
As far as genetic links to the past go, this is one of the most widespread and significant we’ve discovered so far, although there’s much more to explore when it comes to how our genes continue to evolve and affect us.
The same SLC30A9 variation has previously been linked to a higher risk of depression and other mental disorders – so it’s possible that the genes we inherited from the Denisovans also play a role in our mental health.
Again, it’s likely to be down to zinc regulation. Zinc is important in managing the excitability of the nervous system and has been linked to mental health, and it’s a relationship the researchers want to explore further.
“In the future, extending this study to animal models could shed light on this predisposition to mental illness,” says molecular biologist Rubén Vicente from UPF.
