Evolution's cauldron: Duplication, deletion, and rearrangement in the mouse and human genomes
Evolution's cauldron: Duplication, deletion, and rearrangement in the mouse and human genomes
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DOI：
10.1073/pnas.1932072100
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发表时间：
2003-09-30
影响因子：
11.1
通讯作者：
Haussler, D
中科院分区：
文献类型：
--
作者：
Kent, WJ;Baertsch, R;Haussler, D
这项研究通过比较小鼠和人类基因组，检查了从单个碱基到完整染色体的范围内发生的基因组重复、缺失和重排。从全基因组序列比对中，可以明显看出 344 个大的（>100-kb）保守同线性块，但这些块被较小规模的进化事件进一步破碎。排除转座子插入，平均在基因组比对的每个兆碱基中，我们观察到2个倒位、17个重复（5个串联或近串联）、7个转座和200个100个碱基或更多的缺失。这包括 160 个倒位和 75 个长度 > 100 kb 的重复或转位。这些较小事件的频率在组件的成品部分中并没有显着提高。许多较小的转座是经过处理的假基因；我们定义了比对的“同线”子集，排除了这些和其他小规模的转座。这些比对提供的证据表明，人类/小鼠共同祖先中大约 2% 的基因在小鼠中已被删除或部分删除。与人类谱系相比，小鼠中非转座子诱导的基因组复制似乎也略少。尽管我们检测到的一些事件可能是由于当前基因组序列中的错误组装或数据缺失或我们方法的局限性造成的，但大多数可能代表真正的进化事件。为了进行这些观察，我们开发了新的比对技术，可以以稳健的方式处理大间隙并区分直系同源和旁系同源比对。
This study examines genomic duplications, deletions, and rearrangements that have happened at scales ranging from a single base to complete chromosomes by comparing the mouse and human genomes. From whole-genome sequence alignments, 344 large (>100-kb) blocks of conserved synteny are evident, but these are further fragmented by smaller-scale evolutionary events. Excluding transposon insertions, on average in each megabase of genomic alignment we observe two inversions, 17 duplications (five tandem or nearly tandem), seven transpositions, and 200 deletions of 100 bases or more. This includes 160 inversions and 75 duplications or transpositions of length >100 kb. The frequencies of these smaller events are not substantially higher in finished portions in the assembly. Many of the smaller transpositions are processed pseudogenes; we define a "syntenic" subset of the alignments that excludes these and other small-scale transpositions. These alignments provide evidence that approximate to2% of the genes in the human/mouse common ancestor have been deleted or partially deleted in the mouse. There also appears to be slightly less nontransposon-induced genome duplication in the mouse than in the human lineage. Although some of the events we detect are possibly due to misassemblies or missing data in the current genome sequence or to the limitations of our methods, most are likely to represent genuine evolutionary events. To make these observations, we developed new alignment techniques that can handle large gaps in a robust fashion and discriminate between orthologous and paralogous alignments.