Olivera B M, Walker C, Cartier G E, Hooper D, Santos A D, Schoenfeld R, Shetty R, Watkins M, Bandyopadhyay P, Hillyard D R
Department of Biology, University of Utah, Salt Lake City 84112, USA.
Ann N Y Acad Sci. 1999 May 18;870:223-37. doi: 10.1111/j.1749-6632.1999.tb08883.x.
All 500 species of cone snails (Conus) are venomous predators. From a biochemical/genetic perspective, differences among Conus species may be based on the 50-200 different peptides in the venom of each species. Venom is used for prey capture as well as for interactions with predators and competitors. The venom of every species has its own distinct complement of peptides. Some of the interspecific divergence observed in venom peptides can be explained by differential expression of venom peptide superfamilies in different species and of peptide superfamily branching in various Conus lineages into pharmacologic groups with different targeting specificity. However, the striking interspecific divergence of peptide sequences is the dominant factor in the differences observed between venoms. The small venom peptides (typically 10-35 amino acids in length) are processed from larger prepropeptide precursors (ca. 100 amino acids). If interspecific comparisons are made between homologous prepropeptides, the three different regions of a Conus peptide precursor (signal sequence, pro-region, mature peptide) are found to have diverged at remarkably different rates. Analysis of synonymous and nonsynonymous substitution rates for the different segments of a prepropeptide suggests that mutation frequency varies by over an order of magnitude across the segments, with the mature toxin region undergoing the highest rate. The three sections of the prepropeptide which exhibit apparently different mutation rates are separated by introns. This striking segment-specific rate of divergence of Conus prepropeptides suggests a role for introns in evolution: exons separated by introns have the potential to evolve very different mutation rates. Plausible mechanisms that could underlie differing mutational frequency in the different exons of a gene are discussed.
所有500种芋螺（Conus）都是有毒的食肉动物。从生化/遗传学角度来看，不同芋螺物种之间的差异可能基于每个物种毒液中50 - 200种不同的肽。毒液用于捕获猎物以及与捕食者和竞争者进行相互作用。每个物种的毒液都有其独特的肽组合。毒液肽中观察到的一些种间差异可以通过不同物种中毒液肽超家族的差异表达以及各种芋螺谱系中肽超家族分支形成具有不同靶向特异性的药理组来解释。然而，肽序列惊人的种间差异是毒液之间观察到的差异的主要因素。小毒液肽（通常长度为10 - 35个氨基酸）是由较大的前原肽前体（约100个氨基酸）加工而来。如果对同源前原肽进行种间比较，会发现芋螺肽前体的三个不同区域（信号序列、前肽区、成熟肽）以明显不同的速率发生了分化。对前原肽不同片段的同义替换率和非同义替换率的分析表明，突变频率在各片段间相差一个数量级以上，成熟毒素区域的突变率最高。前原肽的这三个表现出明显不同突变率的部分由内含子隔开。芋螺前原肽这种显著的片段特异性分化速率表明内含子在进化中发挥了作用：被内含子隔开的外显子有可能以非常不同的速率进化。文中讨论了可能导致基因不同外显子中突变频率不同的合理机制。
