RT Journal Article
SR Electronic
T1 Human-derived alleles in SOST and RUNX2 3′UTRs cause differential regulation in a bone cell-line model
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.04.21.440797
DO 10.1101/2021.04.21.440797
A1 Moriano, Juan
A1 Martínez-Gil, Núria
A1 Andirkó, Alejandro
A1 Balcells, Susana
A1 Grinberg, Daniel
A1 Boeckx, Cedric
YR 2021
UL http://biorxiv.org/content/early/2021/04/22/2021.04.21.440797.abstract
AB The inquiry into the phenotypic features that set apart human species, such as a light, gracile skeleton and a rounded skull characteristic of Homo sapiens, can now benefit from the examination of ancient genomes. These have added a new layer of analysis allowing the identification of genetic differences between species like ours and our closest extinct relatives. Most of these genetic differences are non-coding changes with unknown functional consequences, and dissecting their putative regulatory effect remains challenging. Here we focus on the three prime untranslated regions (3’UTR), known to play a critical role in messenger RNA regulation and a plausible locus for divergent regulation between Homo species. We report a set of genes with derived 3’UTR changes in either the Homo sapiens or the Neanderthal/Denisovan lineages and experimentally evaluate the impact of 3’UTR variants in four genes: E2F6, GLI3, RUNX2 and SOST. We performed a luciferase reporter assay in a bone cell-line model and found a statistically significant difference for the 3’UTR variants of SOST (Homo sapiens-derived) and RUNX2 (Neanderthal/Denisovan-derived). The differential expression caused by these variants in our experimental model points to species differences in bone mineral density. Thus, this study adds insights into the functional effects of regulatory variants that emerged in recent human evolution.Competing Interest StatementThe authors have declared no competing interest.