Abstract
With more than 1.2 million copies, Alu elements are one of the most important sources of structural variation in primate genomes. Here, we compare the chimpanzee and human genomes to determine the extent of Alu recombination-mediated deletion (ARMD) in the chimpanzee genome since the divergence of the chimpanzee and human lineages (∼6 million y ago). Combining computational data analysis and experimental verification, we have identified 663 chimpanzee lineage-specific deletions (involving a total of ∼771 kb of genomic sequence) attributable to this process. The ARMD events essentially counteract the genomic expansion caused by chimpanzee-specific Alu inserts. The RefSeq databases indicate that 13 exons in six genes, annotated as either demonstrably or putatively functional in the human genome, and 299 intronic regions have been deleted through ARMDs in the chimpanzee lineage. Therefore, our data suggest that this process may contribute to the genomic and phenotypic diversity between chimpanzees and humans. In addition, we found four independent ARMD events at orthologous loci in the gorilla or orangutan genomes. This suggests that human orthologs of loci at which ARMD events have already occurred in other nonhuman primate genomes may be “at-risk” motifs for future deletions, which may subsequently contribute to human lineage-specific genetic rearrangements and disorders.
Highlights
Mobile elements are a major source of genetic diversity in mammals [1,2]
Alu recombination-mediated deletion (ARMD) events in the chimpanzee genome have generated large deletions relative to human-specific ARMD events. Taking deletions in both the human and chimpanzee lineages into account, we suggest that ARMD events may have contributed to genomic and phenotypic diversity between humans and chimpanzees
The 574-bp chimpanzee genomic deletion occurred between the left monomer on the first Alu and the right monomer on the second Alu, whereas the 708-bp genomic deletion in the gorilla happened between the two left monomers of the two Alu elements. These results indicate that at least ;0.9% of chimpanzeespecific ARMD loci (2 of 233 loci which were analyzed by PCR) are shared by the gorilla genome and another ;0.9% are shared by the orangutan genome, due to parallel independent ARMDs at two different time points in two separate primate genomes
Summary
A family of short interspersed elements (SINEs), emerged ;65 million y ago (Mya) and have successfully proliferated in primate genomes with .1.2 million copies [2,3,4,5]. Alu elements consist of a left monomer and a right monomer [2,6]. Each of these monomers independently evolved from 7SL-RNA [7] and subsequently fused into the dimeric Alu element in the primate lineage [6]. Alu elements are known to be associated with primate-specific genomic alterations by several mechanisms, including de novo insertion, insertion-mediated deletion, and unequal recombination between Alu elements [8,9,10,11]. The Alu family consists of a number of subfamilies, which maintain high sequence identity among themselves (70%–99.7%) [12,13,14,15]
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