Shaanxi Key Laboratory of Qinling Ecological Intelligent Monitoring and Protection, School of Ecology and Environment, Northwestern Polytechnical University, Xi'an 710072, China.
Department of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
Mol Biol Evol. 2024 Nov 1;41(11). doi: 10.1093/molbev/msae239.
Limbs are a defining characteristic of tetrapods, yet numerous taxa, primarily among amphibians and reptiles, have independently lost limbs as an adaptation to new ecological niches. To elucidate the genetic factors contributing to this convergent limb loss, we present a 12 Gb chromosome-level assembly of the Banna caecilian (Ichthyophis bannanicus), a limbless amphibian. Our comparative analysis, which includes the reconstruction of amphibian karyotype evolution, reveals constrained gene length evolution in a subset of developmental genes across 3 large genomes. Investigation of limb development genes uncovered the loss of Grem1 in caecilians and Tulp3 in snakes. Interestingly, caecilians and snakes share a significantly larger number of convergent degenerated conserved noncoding elements than limbless lizards, which have a shorter evolutionary history of limb loss. These convergent degenerated conserved noncoding elements overlap significantly with active genomic regions during mouse limb development and are conserved in limbed species, suggesting their essential role in limb patterning in the tetrapod common ancestor. While most convergent degenerated conserved noncoding elements emerged in the jawed vertebrate ancestor, coinciding with the origin of paired appendage, more recent degenerated conserved noncoding elements also contribute to limb development, as demonstrated through functional experiments. Our study provides novel insights into the regulatory elements associated with limb development and loss, offering an evolutionary perspective on the genetic basis of morphological specialization.
四肢是四足动物的一个显著特征，但许多类群，主要是两栖动物和爬行动物，已经独立地失去了四肢，以适应新的生态位。为了阐明导致这种趋同的肢体缺失的遗传因素，我们提供了一种无肢两栖动物版纳盲螈（Ichthyophis bannanicus）的 12Gb 染色体水平组装。我们的比较分析，包括对两栖动物染色体进化的重建，揭示了 3 个大基因组中一组发育基因的受限基因长度进化。对肢体发育基因的研究发现，盲螈中 Grem1 的缺失和蛇中 Tulp3 的缺失。有趣的是，盲螈和蛇比失去肢体的有鳞目蜥蜴共享更多数量的趋同退化保守非编码元件，而后者失去肢体的进化历史较短。这些趋同退化的保守非编码元件与在小鼠肢体发育过程中活跃的基因组区域有显著重叠，并且在有肢体的物种中是保守的，这表明它们在四足动物共同祖先的肢体模式形成中起着至关重要的作用。虽然大多数趋同退化的保守非编码元件出现在有颌脊椎动物的祖先中，与成对附肢的起源同时出现，但最近的退化保守非编码元件也有助于肢体发育，这可以通过功能实验来证明。我们的研究为与肢体发育和缺失相关的调控元件提供了新的见解，为形态特化的遗传基础提供了一个进化的视角。
