She Huishang, Scott Graham R, Fang Yun, Zhao Qingshuo, Meng Fanwei, Qu Yanhua
Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Department of Biology, McMaster University, Hamilton, Ontario, Canada.
Mol Biol Evol. 2025 Apr 30;42(5). doi: 10.1093/molbev/msaf103.
High elevation imposes unrelenting and unavoidable hypoxia on species inhabiting these environments, providing an excellent natural setting for studying convergent or divergent evolution. By integrating measures of phenotypic variation, gene regulation, and functional performance, our study demonstrates that recent colonizers of high-elevation environments exhibit fundamentally different cardiovascular changes compared to long-term natives of these environments. Through the studying of heart morphological phenotypes, we showed that recent colonizers exhibit signs of cardiac hypertrophy, reflected by increased relative heart mass (heart mass/body mass) and cardiomyocyte size compared to their low-elevation relatives. In contrast, native species show no signs of cardiac hypertrophy and instead have 3-fold higher capillary densities than the colonizers, a change that likely enhances tissue oxygen diffusing capacity in the former. Using phylogenetic principal component analysis to quantify multivariate trait divergence, we show that native species are similar in cardiovascular phenotype and underlying gene expression, but differ appreciably from recent colonizers. We further demonstrate, using a functional assay, that differential expression of two genes (IRS2 and AKT1) in a conserved regulatory pathway mediates cardiomyocyte hypertrophy, which could explain the observed variation in cardiomyocyte size between native species and recent colonizers. This regulatory basis of variation in cardiac phenotype involves the differential expression of genes in a cardiomyocyte hypertrophy pathway that is conserved across birds, humans and other mammals. Collectively, our study highlights that evolutionary history is a critical determinant of cardiovascular variation in high-elevation environments.
高海拔对栖息于这些环境中的物种施加了持续且不可避免的缺氧压力，为研究趋同或趋异进化提供了绝佳的自然环境。通过整合表型变异、基因调控和功能表现的测量方法，我们的研究表明，与长期生活在高海拔环境中的本地物种相比，近期才在高海拔环境中定居的物种表现出截然不同的心血管变化。通过研究心脏形态表型，我们发现近期定居者表现出心脏肥大的迹象，这体现在相对于低海拔亲属而言，其相对心脏质量（心脏质量/体重）增加以及心肌细胞大小增大。相比之下，本地物种没有心脏肥大的迹象，相反，它们的毛细血管密度比近期定居者高3倍，这种变化可能增强了前者的组织氧扩散能力。利用系统发育主成分分析来量化多变量性状差异，我们发现本地物种在心血管表型和潜在基因表达方面相似，但与近期定居者有明显差异。我们进一步通过功能测定证明，保守调控途径中两个基因（IRS2和AKT1）的差异表达介导了心肌细胞肥大，这可以解释在本地物种和近期定居者之间观察到的心肌细胞大小差异。心脏表型变异的这种调控基础涉及心肌细胞肥大途径中基因的差异表达，该途径在鸟类、人类和其他哺乳动物中是保守的。总的来说，我们的研究强调进化历史是高海拔环境中心血管变异的关键决定因素。
