Cruciani Véronique, Mikalsen Svein-Ole
Department of Cancer Prevention, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway.
Biol Chem. 2007 Mar;388(3):253-64. doi: 10.1515/BC.2007.028.
We suggest an extension of connexin orthology relationships across the major vertebrate lineages. We first show that the conserved domains of mammalian connexins (encoding the N-terminus, four transmembrane domains and two extracellular loops) are subjected to a considerably more strict selection pressure than the full-length sequences or the variable domains (the intracellular loop and C-terminal tail). Therefore, the conserved domains are more useful for the study of family relationships over larger evolutionary distances. The conserved domains of connexins were collected from chicken, Xenopus tropicalis, zebrafish, pufferfish, green spotted pufferfish, Ciona intestinalis and Halocynthia pyriformis (two tunicates). A total of 305 connexin sequences were included in this analysis. Phylogenetic trees were constructed, from which the orthologies and the presumed evolutionary relationships between the sequences were deduced. The tunicate connexins studied had the closest, but still distant, relationships to vertebrate connexin 36, 39.2, 43.4, 45 and 47. The main structure in the connexin family known from mammals pre-dates the divergence of bony fishes, but some additional losses and gains of connexin sequences have occurred in the evolutionary lineages of subsequent vertebrates. Thus, the connexin gene family probably originated in the early evolution of chordates, and underwent major restructuring with regard to gene and subfamily structures (including the number of genes in each subfamily) during early vertebrate evolution.
我们建议扩展连接蛋白直系同源关系至主要脊椎动物谱系。我们首先表明，哺乳动物连接蛋白的保守结构域（编码N端、四个跨膜结构域和两个细胞外环）比全长序列或可变结构域（细胞内环和C端尾巴）受到更为严格的选择压力。因此，保守结构域在研究更大进化距离上的家族关系时更有用。连接蛋白的保守结构域取自鸡、热带爪蟾、斑马鱼、河豚、绿斑河豚、海鞘和柄海鞘（两种被囊动物）。该分析共纳入305个连接蛋白序列。构建了系统发育树，从中推断出序列之间的直系同源关系和推测的进化关系。所研究的被囊动物连接蛋白与脊椎动物连接蛋白36、39.2、43.4、45和47的关系最为密切，但仍有一定距离。哺乳动物中已知的连接蛋白家族的主要结构早于硬骨鱼的分化，但在随后脊椎动物的进化谱系中发生了一些连接蛋白序列的额外丢失和增加。因此，连接蛋白基因家族可能起源于脊索动物的早期进化，并在早期脊椎动物进化过程中在基因和亚家族结构（包括每个亚家族中的基因数量）方面经历了重大重组。
