When our ancient Homo sapiens ancestors first left Africa for Eurasia some 60,000 years ago, they encountered and mated with some of the other human species that inhabited their new, colder home. Among these were the now-extinct Denisovans, who endowed modern humans with genes that might have helped us adapt to the cold while at the same time increasing our susceptibility to schizophrenia and other mental health disorders.
The rendezvous between humans and other archaic hominid species has left an indelible mark on the genomes of present-day people around the world, with a small percentage of our DNA being directly inherited from both Neanderthals and Denisovans. When examining the genetic makeup of 26 current populations and cross-referencing these against the genomes of our extinct cousins, the authors of a new study came across one of the most widespread traces of Denisovan DNA in modern humans.
According to the researchers’ analysis, present-day populations in all regions apart from Africa contain a particular variant of a gene called SLC30A9, which appears to have been obtained as a direct result of mating with Denisovans in the distant past. The gene itself codes for a protein called ZnT9, which transports zinc across cell membranes.
The variant does not appear in the Neanderthal genome, thus ruling this species out as the source of the gene. At the same time, the researchers found that modern African genomes typically contain an older variant of SLC30A9 that pre-dates the introduction of the Denisovan allele.
The geographical distribution of the Denisovan SLC30A9 gene variant.
Image credit: Jorge Garcia and Elena Bosch
“Through genomic analysis, we noted that the genetic variant observed came from our interbreeding with archaic humans in the past, possibly the Denisovans”, explained study author Ana Roca-Umbert in a statement. “Apparently, the change was beneficial and proved a selective advantage for humans. As a consequence, this variation in the SLC30A9 gene was selected and has reached current populations”, added co-author Jorge Garcia-Calleja.
To examine how the Denisovan variant affects physiology, the team introduced this DNA into human embryonic kidney cells, noting that it altered the amount of zinc that entered key cellular structures such as mitochondria and the endoplasmic reticulum. This, in turn, led to changes in mitochondrial metabolism, preventing “zinc overload” and conveying an overall “gain of function”.
Based on this observation, the study authors suspect that the genetic variant inherited from Denisovans may have helped ancient Homo sapiens become better adapted to the cold. However, because zinc imbalances can cause neurological disorders, it’s possible that the DNA our ancestors acquired when hooking up with other human species may also have left a mark on our mental health.
Confirming this negative side effect, the study authors write that the widespread Denisovan variant “is known to be associated with greater susceptibility to several neuropsychiatric disorders”. These include conditions such as schizophrenia, bipolar disorder, depression, and anorexia nervosa.
Weaving their various findings into a theory regarding the introduction of the Denisovan SLC30A9 variant into the human genome, the researchers “speculate that adaptation to cold may have driven this selection event outside Africa, while also impacting predisposition to neuropsychiatric disorders in modern humans.”
The study is published in the journal PLOS Genetics.
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