Hypoxia Inducible Factor pathway proteins in high-altitude mammals

Trends Biochem Sci. 2023 Nov 29:S0968-0004(23)00286-4. doi: 10.1016/j.tibs.2023.11.002. Online ahead of print.ABSTRACTHumans and other mammals inhabit hypoxic high-altitude locales. In many of these species, genes under positive selection include ones in the Hypoxia Inducible Factor (HIF) pathway. One is PHD2 (EGLN1), which encodes for a key oxygen sensor. Another is HIF2A (EPAS1), which encodes for a PHD2-regulated transcription factor. Recent studies have provided insights into mechanisms for these high-altitude alleles. These studies have (i) shown that selection can occur on nonconserved, unstructured regions of proteins, (ii) revealed that high altitude-associated amino acid substitutions can have differential effects on protein-protein interactions, (iii) provided evidence for convergent evolution by different molecular mechanisms, and (iv) suggested that mutations in different genes can complement one another to produce a set of adaptive phenotypes.PMID:38036336 | DOI:10.1016/j.tibs.2023.11.002

Source: Trends in Biochemical Sciences - November 30, 2023 Category: Biochemistry Authors: Frank S Lee Source Type: research