Table4_Origin and Evolution of the Multifaceted Adherens Junction Component Plekha7.xlsx

Plekha7 is a key adherens junction component involved in numerous functions in mammalian cells. Plekha7 is the most studied member of the PLEKHA protein family, which includes eight members with diverse functions. However, the evolutionary history of Plekha7 remains unexplored. Here, we outline the phylogeny and identify the origins of this gene and its paralogs. We show that Plekha7, together with Plekha4, Plekha5, and Plekha6, belong to a subfamily that we name PLEKHA4/5/6/7. This subfamily is distinct from the other Plekha proteins, which form two additional separate subfamilies, namely PLEKHA1/2 and PLEKHA3/8. Sequence, phylogenetic, exon-intron organization, and syntenic analyses reveal that the PLEKHA4/5/6/7 subfamily is represented by a single gene in invertebrates, which remained single in the last common ancestor of all chordates and underwent gene duplications distinctly in jawless and jawed vertebrates. In the latter species, a first round of gene duplications gave rise to the Plekha4/7 and Plekha5/6 pairs and a second round to the four extant members of the subfamily. These observations are consistent with the 1R/2R hypothesis of vertebrate genome evolution. Plekha7 and Plekha5 also exist in two copies in ray-finned fishes, due to the Teleostei-specific whole genome duplication. Similarities between the vertebrate Plekha4/5/6/7 members and non-chordate sequences are restricted to their N-terminal PH domains, whereas similarities across the remaining protein molecule are only sporadically found among few invertebrate species and are limited to the coiled-coil and extreme C-terminal ends. The vertebrate Plekha4/5/6/7 proteins contain extensive intrinsically disordered domains, which are topologically and structurally conserved in all chordates, but not in non-chordate invertebrates. In summary, our study sheds light on the origins and evolution of Plekha7 and the PLEKHA4/5/6/7 subfamily and unveils new critical information suitable for future functional studies of this still understudied group of proteins.

Plekha7，作为一种关键的粘附连接结构成分，在哺乳动物细胞中参与众多功能。作为PLEKHA蛋白家族中研究最为深入的成员，该家族包含八个成员，各司其职。然而，Plekha7的进化历程尚待挖掘。本研究概述了其系统发育关系，并确定了该基因及其同源基因的起源。我们发现，Plekha7与Plekha4、Plekha5和Plekha6共同构成一个我们称之为PLEKHA4/5/6/7的亚家族，该亚家族与其它PLEKHA蛋白家族成员形成的两个独立亚家族（即PLEKHA1/2和PLEKHA3/8）有所区别。序列分析、系统发育学、外显子-内含子组织以及同源分析揭示了PLEKHA4/5/6/7亚家族在无脊椎动物中仅由单个基因代表，并在所有脊索动物共同的祖先中保持单基因状态，但在无颌和有颌脊椎动物中经历了显著的基因倍增。在后一种物种中，第一轮基因倍增产生了Plekha4/7和Plekha5/6的配对，第二轮倍增则导致了该亚家族现存四个成员的产生。这些观察结果与脊椎动物基因组进化的1R/2R假说相吻合。在辐鳍鱼类中，Plekha7和Plekha5也因Teleostei特异的全基因组倍增而存在两个拷贝。脊椎动物PLEKHA4/5/6/7成员与非脊索动物序列之间的相似性仅限于其N端PH结构域，而剩余蛋白质分子的相似性仅在少数无脊椎动物物种中偶有发现，且局限于螺旋卷曲和极端C端端部。脊椎动物PLEKHA4/5/6/7蛋白含有广泛的内在无序结构域，在所有脊索动物中拓扑和结构上保持保守，但在非脊索动物无脊椎动物中则不然。总之，本研究揭示了Plekha7及其PLEKHA4/5/6/7亚家族的起源与进化，并为未来该类蛋白质群的功能研究提供了新的关键信息。