Mechanisms for evolving hypervariability: The case of conopeptides
Mechanisms for evolving hypervariability: The case of conopeptides
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DOI：
10.1093/oxfordjournals.molbev.a003786
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发表时间：
2001-02-01
影响因子：
10.7
通讯作者：
Fainzilber, M
中科院分区：
文献类型：
--
作者：
Conticello, SG;Gilad, Y;Fainzilber, M
高变性是介导生物体之间相互作用的大基因家族的一个显着特征，例如毒液衍生毒素或免疫球蛋白。为了研究高变异性的进化机制，我们检查了 EST 生成的 170 个不同锥肽序列的组合，这些序列来自 5 种海洋圆锥蜗牛的毒液。这些序列被分配到八个基因家族，由信号域和非翻译区中的保守元件定义。在单个锥肽的表达水平中观察到了数量级的差异，在给定物种中，五到七个转录本通常占超过 50% 的已测序克隆。锥肽前体比对揭示了成熟肽结构域特有的四个显着特征：(1) 核苷酸取代速率加快，(2) 核苷酸取代中颠换相对于转换的偏向，(3) 高变区内半胱氨酸密码子的位置特异性保守，以及 (4) 非同义取代相对于同义取代的优势。我们提出，前三个观察结果主张针对锥肽基因中成熟结构域的增变机制，结合了半胱氨酸密码子特异的保护活性和表现出颠换偏向的诱变聚合酶，例如DNA聚合酶V。高D-n/D-s比率与正选择或多样化选择一致，并且通过种内/种间基因树应急测试进行的进一步分析微弱地支持最近锥肽进化中的多样化选择。由于只有最高表达的转录本根据物种的摄食特异性在基因树中分离，因此多样化选择可能主要作用于这些序列。产生高变异性的靶向突变机制与随后对高表达变体进行多样化选择的作用相结合，可能解释了锥肽的高度变异性和每个物种的大量独特序列。
Hypervariability is a prominent feature of large gene families that mediate interactions between organisms, such as venom-derived toxins or immunoglobulins. In order to study mechanisms for evolution of hypervariability, we examined an EST-generated assemblage of 170 distinct conopeptide sequences from the venoms of five species of marine Conus snails. These sequences were assigned to eight gene families, defined by conserved elements in the signal domain and untranslated regions. Order-of-magnitude differences were observed in the expression levels of individual conopeptides, with five to seven transcripts typically comprising over 50% of the sequenced clones in a given species. The conopeptide precursor alignments revealed four striking features peculiar to the mature peptide domain: (1) an accelerated rate of nucleotide substitution, (2) a bias for transversions over transitions in nucleotide substitutions, (3) a position-specific conservation of cysteine codons within the hypervariable region, and (4) a preponderance of nonsynonymous substitutions over synonymous substitutions. We propose that the first three observations argue for a mutator mechanism targeted to mature domains in conopeptide genes, combining a protective activity specific for cysteine codons and a mutagenic polymerase that exhibits transversion bias, such as DNA polymerase V. The high D-n/D-s ratio is consistent with positive or diversifying selection, and further analyses by intraspecific/interspecific gene tree contingency tests weakly support recent diversifying selection in the evolution of conopeptides. Since only the most highly expressed transcripts segregate in gene trees according to the feeding specificity of the species, diversifying selection might be acting primarily on these sequences. The combination of a targeted mutator mechanism to generate high variability with the subsequent action of diversifying selection on highly expressed variants might explain both the hypervariability of conopeptides and the large number of unique sequences per species.