Eckhart Leopold, Ballaun Claudia, Hermann Marcela, VandeBerg John L, Sipos Wolfgang, Uthman Aumaid, Fischer Heinz, Tschachler Erwin
Department of Dermatology, Medical University of Vienna, Vienna, Austria.
Mol Biol Evol. 2008 May;25(5):831-41. doi: 10.1093/molbev/msn012. Epub 2008 Feb 14.
Proteases of the caspase family play central roles in apoptosis and inflammation. Recently, we have described a new gene encoding caspase-15 that has been inactivated independently in different mammalian lineages. To determine the dynamics of gene duplication and loss in the entire caspase gene family, we performed a comprehensive evolutionary analysis of mammalian caspases. By comparative genomics and reverse transcriptase-polymerase chain reaction analyses, we identified 3 novel mammalian caspase genes, which we tentatively named caspases-16 through -18. Caspase-16, which is most similar in sequence to caspase-14, has been conserved in marsupials and placental mammals, including humans. Caspase-17, which is most similar to caspase-3, has been conserved among fish, frog, chicken, lizard, and the platypus but is absent from marsupials and placental mammals. Caspase-18, which is most similar to caspase-8, has been conserved among chicken, platypus, and opossum but is absent from placental mammals. These gene distribution patterns suggest that, in the evolutionary lineage leading to humans, caspase-17 was lost after the split of protherian and therian mammals and caspase-18 was lost after the split of marsupials and placental mammals. In the canine genome, the number of caspases has been reduced by the fusion of the neighboring genes caspases-1 and -4, resulting in a single coding region. Further lineage-specific gene inactivations were found for caspase-10 in murine rodents and caspase-12 in humans, rabbit, and cow. Lineage-specific gene duplications were found for caspases-1, -3, and -12 in opossum and caspase-4 in primates. Other caspases were generally conserved in all mammalian species investigated. Using the positions of introns as stable characters during recent vertebrate evolution, we define 3 phylogenetic clades of caspase genes: caspases-1/-2/-4/-5/-9/-12/-14/-15/-16 (clade I), caspases-3/-6/-7/-17 (clade II), and caspases-8/-10/-18/CFLAR (clade III). We conclude that gene inactivations have occurred in each of the 3 caspase clades and that gene loss has been as critical as gene duplication in the evolution of the human repertoire of caspases.
半胱天冬酶家族的蛋白酶在细胞凋亡和炎症中起核心作用。最近，我们描述了一个编码半胱天冬酶 -15 的新基因，该基因在不同的哺乳动物谱系中独立失活。为了确定整个半胱天冬酶基因家族中基因复制和丢失的动态过程，我们对哺乳动物半胱天冬酶进行了全面的进化分析。通过比较基因组学和逆转录酶 - 聚合酶链反应分析，我们鉴定出 3 个新的哺乳动物半胱天冬酶基因，我们暂时将其命名为半胱天冬酶 -16 至 -18。与半胱天冬酶 -14 序列最相似的半胱天冬酶 -16，在有袋类动物和包括人类在内的胎盘哺乳动物中得以保留。与半胱天冬酶 -3 最相似的半胱天冬酶 -17，在鱼类、青蛙、鸡、蜥蜴和鸭嘴兽中得以保留，但在有袋类动物和胎盘哺乳动物中不存在。与半胱天冬酶 -8 最相似的半胱天冬酶 -18，在鸡、鸭嘴兽和负鼠中得以保留，但在胎盘哺乳动物中不存在。这些基因分布模式表明，在导致人类的进化谱系中，半胱天冬酶 -17 在原兽类和兽类哺乳动物分化后丢失，半胱天冬酶 -18 在有袋类动物和胎盘哺乳动物分化后丢失。在犬类基因组中，由于相邻基因半胱天冬酶 -1 和 -4 的融合，半胱天冬酶的数量减少，形成了一个单一的编码区域。在鼠类啮齿动物中发现了半胱天冬酶 -10 的进一步谱系特异性基因失活，在人类、兔子和牛中发现了半胱天冬酶 -12 的谱系特异性基因失活。在负鼠中发现了半胱天冬酶 -1、-3 和 -12 的谱系特异性基因复制，在灵长类动物中发现了半胱天冬酶 -4 的谱系特异性基因复制。其他半胱天冬酶在所有研究的哺乳动物物种中通常是保守的。利用内含子位置作为近期脊椎动物进化过程中的稳定特征，我们定义了半胱天冬酶基因的 3 个系统发育分支：半胱天冬酶 -1/-2/-4/-5/-9/-12/-14/-15/-16（分支 I）、半胱天冬酶 -3/-6/-7/-17（分支 II）和半胱天冬酶 -8/-10/-18/CFLAR（分支 III）。我们得出结论，在 3 个半胱天冬酶分支中均发生了基因失活，并且在人类半胱天冬酶库的进化过程中，基因丢失与基因复制同样重要。
