Citrullination Was Introduced into Animals by Horizontal Gene Transfer from Cyanobacteria.

Citrullination Was Introduced into Animals by Horizontal Gene Transfer from Cyanobacteria.
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DOI:
10.1093/molbev/msab317
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发表时间:
2022-02-03
影响因子:
10.7
通讯作者:
Christophorou MA
Christophorou MA
中科院分区:
生物学1区
文献类型:
--
作者:
Cummings TFM;Gori K;Sanchez-Pulido L;Gavriilidis G;Moi D;Wilson AR;Murchison E;Dessimoz C;Ponting CP;Christophorou MA

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蛋白质翻译后修饰为生物系统增加了极大的复杂性。瓜氨酸化是人类生理和病理生理学中的一种关键调节机制,从进化的角度来看是一个谜。虽然瓜氨酸酶(PADI)在脊椎动物中普遍存在,但在酵母、蠕虫和苍蝇中却没有。基于这一分布,PADI被提出水平转移,但这一点一直存在争议。在这里,我们将Padis的进化轨迹映射到动物谱系中。我们提出了一个包含动物和蓝藻PADI的强大的系统发育支持,排除了真菌和其他细菌的同源物。动物和蓝藻的PADI蛋白共享功能相关的初级和三级突触序列,这些序列不同于真菌和放线菌中存在的第二种PADI类型。利用化石记录进行的分子钟计算和序列差异分析估计,蓝藻和动物PADI的最后共同祖先不到10亿年。此外,在垂直下降的假设下,PADI序列在这一进化时间框架内的变化是不合时宜的,即使与可能的内共生体基因转移、线粒体蛋白质和一些生命中最高度保守的序列相比也是如此。有证据表明,PADI是通过水平基因转移(HGT)从蓝藻导入动物体内的。祖先蓝藻PADI具有酶活性并能催化真核蛋白的瓜氨酸化,这表明PADI HGT事件为动物的调节系统引入了一种新的催化能力。这项研究揭示了多效性蛋白质修饰的不同寻常的进化。
Protein posttranslational modifications add great sophistication to biological systems. Citrullination, a key regulatory mechanism in human physiology and pathophysiology, is enigmatic from an evolutionary perspective. Although the citrullinating enzymes peptidylarginine deiminases (PADIs) are ubiquitous across vertebrates, they are absent from yeast, worms, and flies. Based on this distribution PADIs were proposed to have been horizontally transferred, but this has been contested. Here, we map the evolutionary trajectory of PADIs into the animal lineage. We present strong phylogenetic support for a clade encompassing animal and cyanobacterial PADIs that excludes fungal and other bacterial homologs. The animal and cyanobacterial PADI proteins share functionally relevant primary and tertiary synapomorphic sequences that are distinct from a second PADI type present in fungi and actinobacteria. Molecular clock calculations and sequence divergence analyses using the fossil record estimate the last common ancestor of the cyanobacterial and animal PADIs to be less than 1 billion years old. Additionally, under an assumption of vertical descent, PADI sequence change during this evolutionary time frame is anachronistically low, even when compared with products of likely endosymbiont gene transfer, mitochondrial proteins, and some of the most highly conserved sequences in life. The consilience of evidence indicates that PADIs were introduced from cyanobacteria into animals by horizontal gene transfer (HGT). The ancestral cyanobacterial PADI is enzymatically active and can citrullinate eukaryotic proteins, suggesting that the PADI HGT event introduced a new catalytic capability into the regulatory repertoire of animals. This study reveals the unusual evolution of a pleiotropic protein modification.
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