As our ancient human ancestors migrated out of Africa about 60,000 years ago, they encountered Denisovans, a subspecies of archaic humans, in Asia. This event led to some type of interaction that resulted in offspring, and modern humans still carry some of the evidence of that event in their genome. A new study has identified a genetic variant found in modern humans that seems to have originated with Denisovans, and may have helped ancient humans adapt to cold temperatures. This genetic variant has an influence on the regulation of zinc, as well as cellular metabolism, and might also be related to mental conditions like depression or schizophrenia. The findings have been reported in PLOS Genetics.
A genetic analysis showed that this variant originated when there was interbreeding with archaic humans, said co-first study author Ana Roca-Umbert, of Universitat Pompeu Fabra (UPF). But Neanderthals were not the source of this change in the genetic sequence.
The change stuck around in the genome, however, so it likely conferred some advantage, noted co-first study author Jorge Garcia-Calleja of UPF.
Zinc is important to human physiology, but its regulation is still not well understood. We do know that deficiencies in zinc can lead to immune or neurological disorders, as well as growth problems.
The genetic variation highlighted in this work is found in a gene called SLC30A9, in populations in Europe, Asia, and the Americas. It is far less common in Africa. This Denisovan variant may be one of the most geographically widespread, the researchers suggested, and affects all populations outside of Africa, added co-study leader Elena Bosch, a principal investigator at the Institut de Biologia Evolutiva (IBF).
The investigators determined that the Denisovan SLC30A9 variant influences the transport of zinc in human cells. In this study, the researchers found that the gene variant leads to a new distribution of zinc in cells, causing changes in cellular metabolism. The variant seems to affect mitochondria and the endoplasmic reticulum, which are cellular organelles, and boosts their ability to withstand adverse climactic conditions.
"The observed phenotype leads us to think of a possible adaptation to the cold," explained co-study leader Rubén Vicente, a principal investigator at UPF.
The transport of zinc is also related to excitability in the nervous system, and is connected to mental health and stability. The genetic variation identified in this study is in a gene that is expressed all over the body. The variant is also associated with an increase in the risk of a variety of mental health issues including anorexia nervosa, bipolar disorder, depression, obsessive compulsive disorder, schizophrenia, hyperactivity, and autism spectrum disorder.
Further research on this variant may help us learn more about predispositions to mental illnesses.
Sources: Universitat Pompeu Fabra - Barcelona, PLOS Genetics
