Data_Sheet_1_Natural selection and convergent evolution of the HOX gene family in Carnivora.ZIP

HOX genes play a central role in the development and regulation of limb patterns. For mammals in the order Carnivora, limbs have evolved in different forms, and there are interesting cases of phenotypic convergence, such as the pseudothumb of the giant and red pandas, and the flippers or specialized limbs of the pinnipeds and sea otter. However, the molecular bases of limb development remain largely unclear. Here, we studied the molecular evolution of the HOX9 ~ 13 genes of 14 representative species in Carnivora and explored the molecular evolution of other HOX genes. We found that only one limb development gene, HOXC10, underwent convergent evolution between giant and red pandas and was thus an important candidate gene related to the development of pseudothumbs. No signals of amino acid convergence and natural selection were found in HOX9 ~ 13 genes between pinnipeds and sea otter, but there was evidence of positive selection and rapid evolution in four pinniped species. Overall, few HOX genes evolve via natural selection or convergent evolution, and these could be important candidate genes for further functional validation. Our findings provide insights into potential molecular mechanisms of the development of specialized pseudothumbs and flippers (or specialized limbs).

同源框（HOX）基因在肢体模式的发育与调控中发挥核心作用。对于食肉目（Carnivora）哺乳动物而言，其肢体已演化出多样形态，且存在诸多有趣的表型趋同案例，例如大熊猫与小熊猫的伪拇指，以及鳍足类动物与海獭的鳍状肢或特化肢体。然而，肢体发育的分子基础在很大程度上仍未明确。本研究针对14种食肉目代表性物种的HOX9~13基因开展分子演化分析，并探究了其他HOX基因的分子演化特征。研究发现，仅肢体发育基因HOXC10在大熊猫与小熊猫之间发生了趋同演化，因此该基因是与伪拇指发育相关的重要候选基因。在鳍足类动物与海獭的HOX9~13基因中，未检测到氨基酸趋同演化与自然选择信号，但4种鳍足类动物的HOX基因存在正选择与快速演化的证据。总体而言，仅少数HOX基因通过自然选择或趋同演化发生演化，这些基因可作为后续功能验证的重要候选靶点。本研究结果为特化伪拇指与鳍状肢（或特化肢体）的发育潜在分子机制提供了新的见解。