Table2_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，作为哺乳动物细胞中诸多功能的关键粘附连接组分，是PLEKHA蛋白家族中最受研究的成员。该家族包含八个成员，各具不同的功能。然而，Plekha7的进化历程尚未被深入探讨。本研究中，我们梳理了其系统发育树，并确定了该基因及其拟似物的起源。我们发现，Plekha7与Plekha4、Plekha5和Plekha6共同构成了一个名为PLEKHA4/5/6/7的亚家族，这一亚家族与其他PLEKHA蛋白家族成员有所区别，后者形成了两个独立的亚家族，即PLEKHA1/2和PLEKHA3/8。通过序列、系统发育、外显子-内含子组织和同源分析，我们揭示PLEKHA4/5/6/7亚家族在无脊椎动物中仅由一个基因代表，在所有脊索动物共同的祖先中保持单一状态，而在无颌和有颌脊椎动物中经历了显著的不同基因复制。在后者中，第一轮基因复制产生了Plekha4/7和Plekha5/6这对，第二轮复制则导致了该亚家族现存四个成员的出现。这些观察结果与脊椎动物基因组进化的1R/2R假说相吻合。Plekha7和Plekha5在辐鳍鱼类中也存在两个副本，这是由于硬骨鱼特异的全基因组复制所致。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，而蛋白质分子剩余部分的相似性仅零星地存在于少数无脊椎动物物种中，且限于螺旋状结构和极端C端末端。脊椎动物PLEKHA4/5/6/7蛋白含有广泛的内在无序结构域，这些结构域在所有脊索动物中拓扑和结构上均保持保守，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亚家族的起源和进化，并揭示了关于这一仍被低估的蛋白群未来功能研究的重要新信息。