Chromosomal Inversions between Human and Chimpanzee Lineages Caused by Retrotransposons

Abstract

The long interspersed element-1 (LINE-1 or L1) and Alu elements are the most abundant mobile elements comprising 21% and 11% of the human genome, respectively. Since the divergence of human and chimpanzee lineages, these elements have vigorously created chromosomal rearrangements causing genomic difference between humans and chimpanzees by either increasing or decreasing the size of genome. Here, we report an exotic mechanism, retrotransposon recombination-mediated inversion (RRMI), that usually does not alter the amount of genomic material present. Through the comparison of the human and chimpanzee draft genome sequences, we identified 252 inversions whose respective inversion junctions can clearly be characterized. Our results suggest that L1 and Alu elements cause chromosomal inversions by either forming a secondary structure or providing a fragile site for double-strand breaks. The detailed analysis of the inversion breakpoints showed that L1 and Alu elements are responsible for at least 44% of the 252 inversion loci between human and chimpanzee lineages, including 49 RRMI loci. Among them, three RRMI loci inverted exonic regions in known genes, which implicates this mechanism in generating the genomic and phenotypic differences between human and chimpanzee lineages. This study is the first comprehensive analysis of mobile element bases inversion breakpoints between human and chimpanzee lineages, and highlights their role in primate genome evolution.

Pico-inplace-inversions between human and chimpanzee

“…Chaisson et al (2006) reported 426 inversions, and the refined method of Ma et al (2006) identified a similar number of inversions; however, only ∼59% of inversions were consistent in these studies (Chaisson et al, 2006). Lee et al (2008) reported 323 inversions among which 252 could be clearly characterized. These discrepancies indicate that identifying inversions is difficult, even for closely related species.…”

“…Although human and chimpanzee are the most closely related species, the studies on micro-inversions between them (Chaisson et al, 2006;Feuk et al, 2005;Lee et al, 2008;Ma et al, 2006) showed large discrepancies. The earliest result reported 1576 putative inversions (Feuk et al, 2005), and later, it was found that the majority of these were artifacts (Chaisson et al, 2006;Kolb et al, 2009).…”

Molecular cytogenetic and genomic insights into chromosomal evolution

“…Although Robertsonian fusions and fissions appear frequently in studies of chromosomal rearrangement (as measured by changes in chromosome number), one of the most striking findings of comparative genomics is the high incidence of micro-inversions in the different genomes (Feuk et al, 2005;Lee et al, 2008;Zhao and Bourque, 2009). It may be that this largely undetected class of variation (inversions cannot be distinguished using whole chromosome painting, a data set that provides much of the basis for the recognition of ancestral constructs in Placentalia) functions as genomically localized barriers to recombination.…”

Structural and Functional Divergence of a 1-Mb Duplicated Region in the Soybean (Glycine max) Genome and Comparison to an Orthologous Region fromPhaseolus vulgaris

“…More structural changes (deletions) were found in the two Gm15 intervals, where there was higher transposon density, suggesting a correlation between structural changes and transposable elements. It is known that transposons can induce major genome rearrangements, including deletions, duplications, inversions, macrotransposition, and reciprocal translocations (Gray, 2000;Caceres et al, 2001;Lonnig and Saedler, 2002;Huang and Dooner, 2008;Lee et al, 2008;Zhang et al, 2009). We hypothesize that Gm15, with a higher transposon density, underwent more extensive structural changes (i.e., higher density of LTR retrotransposon, solo LTRs, and lower gene retention rate) and that transposable elements were likely an active force in this remodeling of a homoeologous chromosome in soybean (see Supplemental Figure 17 online).…”