Abundance of ultramicro inversions within local alignments between human and chimpanzee genomes

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.Chromosomal inversion, a type of genetic rearrangement involving the inversion of a chromosome segment, is one of the most important causes of genomic changes. Inversions have been identified as phylogenetic signatures since the first third of the twentieth century [1] and are thought to have affected phenotypic evolution [2]. While large-size inversions (macroscopic inversions), microscopically-detectable and/or visible in genetic maps, were identified early on [1,3], the recent abundance of genomic sequences and progress in sequence