Hypoxia Inducible Factor pathway proteins in high-altitude mammals.
Trends Biochem Sci
; 49(1): 79-92, 2024 01.
Article
in En
| MEDLINE
| ID: mdl-38036336
ABSTRACT
Humans 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adaptation, Physiological
/
Altitude
Limits:
Animals
/
Humans
Language:
En
Journal:
Trends Biochem Sci
Year:
2024
Type:
Article