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.
高原和海洋哺乳动物生活在不同的生态环境中，但都面临同一个挑战：低氧环境。为应对低氧，这些动物在肺部形态上展现出类似的适应性变化，尤其是肺部具有大量松弛排布的弹性纤维。在该研究中，我们利用比较基因组学和趋同进化分析，从多个角度探讨高原和海洋哺乳动物如何适应肺纤维化和低氧环境。我们观察到某些基因家族在高原和海洋哺乳动物中出现了显著的趋同扩张或收缩，这与肺纤维化等过程密切相关。特别是，在角蛋白基因家族中的 KRT17和 KRT14可能与这些耐低氧哺乳动物肺部丰富的弹性纤维表型相关。通过选择压力分析和氨基酸替代分析，我们识别了多个基因在这些物种中经历了趋同的加速进化、正选择和氨基酸替换，且这些基因的功能与低氧环境适应相关。具体来说， ZFP36L1、 FN1和 NEDD9基因的趋同进化促进了高原和海洋哺乳动物肺部丰富的弹性纤维形成，有助于其适应低氧环境。此外，我们还注意到在与精子发育、分化和精子生成相关的基因中存在趋同的氨基酸替代和基因丢失。例如， SLC26A3基因中的氨基酸替代和 CFAP47的假基因化（PCR验证）在高原和海洋哺乳动物中被识别。这些遗传变化可能与这些动物的生殖能力变化相关。总体而言，我们的研究为高原和海洋哺乳动物对低氧环境的适应提供了新的视角，特别是关注肺纤维化的适应性变化。.
Keywords: Convergent evolution; High-altitude mammals; Hypoxia; Marine mammals; Pulmonary fibrosis.