Genetic Genealogy & Ancient DNA (TITLES/ABSTRACTS)

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Human genetic adaptation related to cellular zinc homeostasis
Ana Roca-Umbert et al. PLoS Genet. 2023.
Authors
Ana Roca-Umbert 1, Jorge Garcia-Calleja 1, Marina Vogel-González 2, Alejandro Fierro-Villegas 2, Gerard Ill-Raga 2, Víctor Herrera-Fernández 2, Anja Bosnjak 2, Gerard Muntané 1 3 4, Esteban Gutiérrez 2, Felix Campelo 5, Rubén Vicente 2, Elena Bosch 1 4
https://pubmed.ncbi.nlm.nih.gov/37747921

SLC30A9 encodes a ubiquitously zinc transporter (ZnT9) and has been consistently suggested as a candidate for positive selection in humans. However, no direct adaptive molecular phenotype has been demonstrated. Our results provide evidence for directional selection operating in two major complementary haplotypes in Africa and East Asia. These haplotypes are associated with differential gene expression but also differ in the Met50Val substitution (rs1047626) in ZnT9, which we show is found in homozygosis in the Denisovan genome and displays accompanying signatures suggestive of archaic introgression. Although we found no significant differences in systemic zinc content between individuals with different rs1047626 genotypes, we demonstrate that the expression of the derived isoform (ZnT9 50Val) in HEK293 cells shows a gain of function when compared with the ancestral (ZnT9 50Met) variant. Notably, the ZnT9 50Val variant was found associated with differences in zinc handling by the mitochondria and endoplasmic reticulum, with an impact on mitochondrial metabolism. Given the essential role of the mitochondria in skeletal muscle and since the derived allele at rs1047626 is known to be associated with greater susceptibility to several neuropsychiatric traits, we propose that adaptation to cold may have driven this selection event, while also impacting predisposition to neuropsychiatric disorders in modern humans.

https://www.phys.org/news/2023-10-geneti...ental.html

Denisovan SLC30A9 gene in humans and its influence on adaption to cold, high altitudes, mental health.

"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," adds Jorge Garcia-Calleja, co-first author of the study."

"Although the variant was established in Asia as a result of interbreeding between Denisovans and Homo sapiens, it also spread to European and native American populations. In fact, it is found in populations all over the planet, although, in the case of African populations, it is much less frequent."

"The team points out that it is probably the Denisovan genetic adaptation to have the greatest geographical scope discovered to date. "For example, a variant in the EPAS1 gene inherited from the Denisovans allows adapting to life at altitude, but is found only in Tibetans. However, in our case, the impact extends to all populations outside Africa," Bosch concludes.