Convergent evolution in high-altitude and marine mammals: Molecular adaptations to pulmonary fibrosis and hypoxia

Abstract

High-altitude and marine mammals inhabit distinct ecosystems but share a common challenge: hypoxia. To survive in low-oxygen environments, these species have evolved similar phenotypic pulmonary adaptations, characterized by a high density of elastic fibers. In this study, we explored the molecular mechanisms underlying these adaptations, focusing on pulmonary fibrosis and hypoxia tolerance through comparative genomics and convergent evolution analyses. We observed significant expansions and contractions in certain gene families across both high-altitude and marine mammals, closely associated with processes involved in pulmonary fibrosis. Notably, members of the keratin gene family, such as KRT17 and KRT14, appear to be associated with the development of the dense elastic fiber phenotype observed in the lungs of hypoxia-tolerant mammals. Through selection pressure and amino acid substitution analyses, we identified multiple genes exhibiting convergent accelerated evolution, positive selection, and amino acid substitution in these species, associated with adaptation to hypoxic environments. Specifically, the convergent evolution of ZFP36L1, FN1, and NEDD9 was found to contribute to the high density of elastic fibers in the lungs of both high-altitude and marine mammals, facilitating their hypoxia tolerance. Additionally, we identified convergent amino acid substitutions and gene loss events associated with sperm development, differentiation, and spermatogenesis, such as amino acid substitutions in SLC26A3 and pseudogenization of CFAP47, as confirmed by PCR. These genetic alterations may be linked to changes in the reproductive capabilities of these animals. Overall, this study offers novel perspectives on the genetic and molecular adaptations of high-altitude and marine mammals to hypoxic environments, with a particular emphasis on pulmonary fibrosis.

Keywords: Convergent evolution; High-altitude mammals; Hypoxia; Marine mammals; Pulmonary fibrosis.

Figure 1

Phylogenetic tree and divergence times based on fourfold degenerate sites of 5 243 one-to-one orthologous genes Red font and “yes” represent species living in low-oxygen environments, black font and “no” represent closely related species.

Figure 2

Gene family expansion and contraction in 23 mammalian species A: Phylogenetic tree of 23 mammalian species displaying gene family expansions (blue) and contractions (green). Hypoxia-tolerant species are indicated in red and labeled “yes”, while closely related species are shown in black and labeled “no”. B: Significant gene family expansions ( P<0.05) in hypoxia-tolerant mammals. X-axis represents hypoxia-tolerant species, Y-axis represents expanded gene families. Filled circles indicate significant expansions, unfilled circles denote no significant expansion. C: Functional annotation of significantly expanded gene families was performed using eggNOG-mapper v.2 ( Cantalapiedra et al., 2021) and gene enrichment analysis of GO biological processes was performed using Metascape.

Figure 3

Functional enrichment of convergent accelerated evolution genes and convergent positive selection genes in GO biological processes A: GO term enrichment analysis of convergent REGs. B: GO term enrichment analysis of convergent PSGs. Circles represent quantities of different genes, size of each circle is proportional to number of genes, color transition of circles from blue to red indicates an increase in –log ₁₀ ( P-value).

Figure 4

Convergent amino acid substitution and GO enrichment analysis A: GO term enrichment analysis of convergent amino acid substitution genes. B: Convergent amino acid substitution sites in SLC26A3 gene.

Figure 5

Convergent gene loss and GO term enrichment analysis A: Number of gene losses in whales, other marine mammals, high-altitude mammals, and their close relatives. Circle sizes represent quantity of gene loss, with blue circles for whales, green for other marine mammals, pink for high-altitude mammals, and colorless for close relatives. Animal silhouettes were obtained from PhyloPic (https://www.phylopic.org/). B: Venn diagram of number of genes commonly lost among cetaceans, other marine mammals, and high-altitude mammals. C: GO term enrichment analysis of convergent loss genes.