Biomedicinal Information Research Center, National Institute of Advanced Industrial Science and Technology, Aomi 2-4-7, Koto-ku, Tokyo, Japan.
BMC Evol Biol. 2011 Oct 19;11:308. doi: 10.1186/1471-2148-11-308.
Chromosomal inversion is one of the most important mechanisms of evolution. Recent studies of comparative genomics have revealed that chromosomal inversions are abundant in the human genome. While such previously characterized inversions are large enough to be identified as a single alignment or a string of local alignments, the impact of ultramicro inversions, which are such short that the local alignments completely cover them, on evolution is still uncertain.
In this study, we developed a method for identifying ultramicro inversions by scanning of local alignments. This technique achieved a high sensitivity and a very low rate of false positives. We identified 2,377 ultramicro inversions ranging from five to 125 bp within the orthologous alignments between the human and chimpanzee genomes. The false positive rate was estimated to be around 4%. Based on phylogenetic profiles using the primate outgroups, 479 ultramicro inversions were inferred to have specifically inverted in the human lineage. Ultramicro inversions exclusively involving adenine and thymine were the most frequent; 461 inversions (19.4%) of the total. Furthermore, the density of ultramicro inversions in chromosome Y and the neighborhoods of transposable elements was higher than average. Sixty-five ultramicro inversions were identified within the exons of human protein-coding genes.
We defined ultramicro inversions as the inverted regions equal to or smaller than 125 bp buried within local alignments. Our observations suggest that ultramicro inversions are abundant among the human and chimpanzee genomes, and that location of the inversions correlated with the genome structural instability. Some of the ultramicro inversions may contribute to gene evolution. Our inversion-identification method is also applicable in the fine-tuning of genome alignments by distinguishing ultramicro inversions from nucleotide substitutions and indels.
染色体倒位是进化的最重要机制之一。比较基因组学的最新研究表明，染色体倒位在人类基因组中非常丰富。虽然以前已经确定的倒位足够大，可以被识别为单个比对或一系列局部比对，但长度非常短以至于局部比对完全覆盖它们的超微倒位对进化的影响仍然不确定。
在这项研究中，我们开发了一种通过局部比对扫描来识别超微倒位的方法。该技术具有很高的灵敏度和非常低的假阳性率。我们在人类和黑猩猩基因组的同源比对中鉴定出了 2377 个长度在 5 到 125 个碱基之间的超微倒位。假阳性率估计约为 4%。基于使用灵长类动物外群的系统发育轮廓，推断出 479 个超微倒位是在人类谱系中特异性倒位的。完全由腺嘌呤和胸腺嘧啶组成的超微倒位最为常见；总共有 461 个倒位（19.4%）。此外，超微倒位在染色体 Y 中的密度和转座元件的周围区域高于平均值。在人类蛋白编码基因的外显子中鉴定出 65 个超微倒位。
我们将超微倒位定义为等于或小于 125 个碱基的倒置区域，这些区域被埋在局部比对中。我们的观察结果表明，超微倒位在人类和黑猩猩基因组中非常丰富，而且倒位的位置与基因组结构的不稳定性相关。一些超微倒位可能有助于基因进化。我们的倒位识别方法也适用于通过将超微倒位与核苷酸替换和插入缺失区分开来，对基因组比对进行微调。
