BMP4的适应性进化是鲸类动物鳍前肢变化的潜在机制。

IF 4 1区 生物学 Q1 ZOOLOGY
Yao Liu, Luo-Ying Deme, Jia Liu, Shi-Xia Xu, Guang Yang
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引用次数: 0

摘要

脊椎动物四肢经历了深刻的形态多样化,使其能够适应广泛的生态位。在海洋哺乳动物中,高度特化的鳍状前肢的进化代表了与水生栖息地相关的深刻的结构转变。据推测,这种适应部分是由于肢体发育过程中指骨间细胞凋亡受到抑制,尽管其潜在的遗传机制尚不清楚。本研究研究了三个关键骨形态发生蛋白基因BMP2、BMP4和BMP7的进化动力学和功能后果,这些基因在胚胎肢体发育过程中调节指骨间充质间质细胞的凋亡,以确保指骨间组织的正常分化。比较基因组分析显示,鲸类动物祖先谱系中BMP4和BMP7的进化显著加速,其中两个阳性选择位点(V79I和H247R)涉及鲸类动物特异性氨基酸替换,位于BMP4 TGF-β前肽功能域。体外实验证实,鲸类动物特异性BMP4突变显著破坏了正常细胞的凋亡和增殖,并改变了BMP信号通路中下游凋亡相关因子的转录和蛋白表达,包括细胞色素c (Cyt c)、BCL2相关X和b细胞淋巴瘤2。BMP4突变对凋亡抑制的显著影响突出了鲸类动物肢芽间充质组织发育和鳍状前肢表型出现的潜在作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Adaptive evolution of BMP4 as a potential mechanism for flipper forelimb changes in cetaceans.

Vertebrate limbs have undergone profound morphological diversification, enabling adaptations to a broad spectrum of ecological niches. In marine mammals, the evolution of highly specialized flipper-like forelimbs represents a profound structural transformation associated with aquatic habitats. This adaptation has been hypothesized to result, in part, from the inhibition of interphalangeal cell apoptosis during limb development, although the underlying genetic mechanism remains poorly understood. This study investigated the evolutionary dynamics and functional consequences of three key bone morphogenetic protein genes, BMP2, BMP4, and BMP7, which regulate apoptosis in interphalangeal mesenchymal stromal cells during embryonic limb development to ensure proper differentiation of interphalangeal tissues. Comparative genomic analysis revealed significantly accelerated evolution for BMP4 and BMP7 in the cetacean ancestral lineage, with two positively selected sites (V79I and H247R) involved in cetacean-specific amino acid substitutions located in the TGF-β propeptide functional domain in BMP4. In vitro assays confirmed that cetacean-specific BMP4 mutations significantly disrupted normal cell apoptosis and proliferation and altered the transcription and protein expression of downstream apoptosis-related factors, including cytochrome c (Cyt c), BCL2 associated X, and B-cell lymphoma 2, within the BMP signaling pathway. The significant influence of BMP4 mutations on apoptotic inhibition highlights a potential role in the development of limb bud mesenchymal tissue and the emergence of the flipper forelimb phenotype in cetaceans.

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来源期刊
Zoological Research
Zoological Research Medicine-General Medicine
CiteScore
7.60
自引率
10.20%
发文量
1937
审稿时长
8 weeks
期刊介绍: Established in 1980, Zoological Research (ZR) is a bimonthly publication produced by Kunming Institute of Zoology, the Chinese Academy of Sciences, and the China Zoological Society. It publishes peer-reviewed original research article/review/report/note/letter to the editor/editorial in English on Primates and Animal Models, Conservation and Utilization of Animal Resources, and Animal Diversity and Evolution.
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