Molecular Evolution of <em>Drosophila</em> Cuticular Protein Genes

Several multigene families have been described that together encode scores of structural cuticular proteins in Drosophila, although the functional significance of this diversity remains to be explored. Here I investigate the evolutionary histories of several multigene families (CPR, Tweedle, CPLCG, and CPF/CPFL) that vary in age, size, and sequence complexity, using sequenced Drosophila genomes and mosquito outgroups. My objective is to describe the rates and mechanisms of ‘cuticle-ome’ divergence, in order to identify conserved and rapidly evolving elements. I also investigate potential examples of interlocus gene conversion and concerted evolution within these families during Drosophila evolution. The absolute rate of change in gene number (per million years) is an order of magnitude lower for cuticular protein families within Drosophila than it is among Drosophila and the two mosquito taxa, implying that major transitions in the cuticle proteome have occurred at higher taxonomic levels. Several hotspots of intergenic conversion and/or gene turnover were identified, e.g. some gene pairs have independently undergone intergenic conversion within different lineages. Some gene conversion hotspots were characterized by conversion tracts initiating near nucleotide repeats within coding regions, and similar repeats were found within concertedly evolving cuticular protein genes in Anopheles gambiae. Rates of amino-acid substitution were generally severalfold higher along the branch connecting the Sophophora and Drosophila species groups, and 13 genes have Ka/Ks significantly greater than one along this branch, indicating adaptive divergence. Insect cuticular proteins appear to be a source of adaptive evolution within genera and, at higher taxonomic levels, subject to periods of gene-family expansion and contraction followed by quiescence. However, this relative stasis is belied by hotspots of molecular evolution, particularly concerted evolution, during the diversification of Drosophila. The prominent association between interlocus gene conversion and repeats within the coding sequence of interacting genes suggests that the latter promote strand exchange.已有研究报道了多个多基因家族，它们在果蝇属（Drosophila）中共同编码数十种结构表皮蛋白，不过这种多样性的功能意义仍有待探究。本研究利用已测序的果蝇属基因组以及作为外类群的蚊子基因组，对CPR、Tweedle、CPLCG、CPF/CPFL这几个在起源年代、家族规模与序列复杂度上存在差异的多基因家族的演化历史展开研究。本研究的目标是阐明表皮蛋白组（cuticle-ome）分化的速率与机制，以此识别保守元件与快速演化元件。此外，本研究还探究了果蝇属演化过程中这些家族内可能存在的基因座间基因转换与协同演化案例。相较于果蝇属内部以及果蝇属与两类蚊子类群之间的情况，果蝇属内表皮蛋白家族的基因数量绝对变化速率（每百万年）低一个数量级，这表明表皮蛋白质组的重大转变发生在更高的分类阶元层面。本研究已鉴定出多个基因间转换和/或基因更新的热点区域，例如部分基因对在不同演化支系中独立发生了基因间转换。部分基因转换热点区域的转换片段起始于编码区内的核苷酸重复序列附近，而在冈比亚按蚊（Anopheles gambiae）的协同演化表皮蛋白基因中也发现了类似的重复序列。连接Sophophora亚属与果蝇亚属的演化支上，氨基酸替换速率通常高出数倍；该支系上有13个基因的Ka/Ks比值显著大于1，表明存在适应性分化。昆虫表皮蛋白似乎是属内适应性演化的来源之一，而在更高的分类阶元层面，它们会经历基因家族扩张、收缩随后进入静止期的周期。不过，在果蝇属的多样化过程中，分子演化热点（尤其是协同演化）的存在打破了这种相对静止的状态。基因座间基因转换与互作基因编码区内的重复序列之间存在显著关联，这表明后者能够促进链交换过程。