Molecular sequence evolutionary analyses of the EGLN1 gene in Capra falconeri (Markhor), a gene involved in high altitude adaptation

Abstract

The Markhor (Capra falconeri), Pakistan's national animal, faces critical endangerment challenges despite its remarkable resilience in inhabiting high-altitude terrains. Distinguished by its majestic horn morphology, elongated shoulder structure, and unique habitat preferences, the Markhor stands apart from conventional domestic goats and other caprine species. This study delves into the pivotal role of the EGLN1 gene in mediating high-altitude adaptation, extending its investigation to other species with comparable traits, including the snow leopard. EGLN1 encodes the PHD2 protein (Prolyl hydroxylase domain containing protein 2), a component of the oxygen-sensing system that expedites the degradation of HIF-α (Hypoxia-Inducible Factor alpha). In hypoxic environments characterized by low oxygen levels, EGLN1 activity diminishes, permitting HIF-α to evade hydroxylation at critical proline sites, consequently leading to HIF-α's stabilization.To unravel the genetic underpinnings of this intricate adaptive mechanism, we conducted a comprehensive evolutionary analysis of PHD2 protein homologs across diverse sarcopterygian species, encompassing both invertebrates and high-altitude adapted animals like the Tibetan Human, Markhor, and snow leopard. By subjecting EGLN1 coding DNA data to evolutionary rate analysis, we deciphered prevailing selection constraints. Our findings underscore the prevalence of negative selection acting upon the EGLN1 gene, signifying its functional significance in maintaining high-altitude adaptability.Employing MEGA7, ancestral sequences of EGLN1 were reconstructed, and subsequent multiple sequence alignments facilitated the identification of species-specific amino acid substitutions in the snow leopard and Markhor. Notably, while no distinct amino acid changes were observed in the Markhor, a solitary alteration was identified in the goat's EGLN1 protein compared to the Markhor's protein.This investigation not only enhances our understanding of the adaptive traits characterizing the Markhor and other high-altitude dwellers but also uncovers the intricate genetic foundations that underlie their unique capabilities. The intricate interplay between EGLN1 and HIF-α opens avenues for further research into the molecular mechanisms orchestrating high-altitude adaptation across diverse species.