Retrotransposon mediated genomic variation in the human and chimpanzee lineages

LINE-1 (Long INterspersed Element-1 or L1) and Alu elements are important sources of structural variation in primate genomes because they are highly active retrotransposons with copy numbers of ~520,000 and \u3e1.2 million within the human genome, respectively. Although the bulk of these elements have resided in their respective host genomes for a long time, and have thus accumulated random mutations, overall these elements retain high levels of sequence identity among themselves. The presence of many nearly-identical retrotransposons located close to each other (e.g., Alu-Alu or L1-L1 pairs) disposes their host genomes to unequal homologous DNA recombination events that generate genomic deletions and inversions of varying sizes. Through computational comparisons of the human and chimpanzee genome sequences, and using rhesus macaque and orangutan genome sequences as outgroups, we have identified species-specific genomic variation. In the first analysis, we identified human and chimpanzee-specific L1s and examined their sequence evolution. We show that L1 retrotransposition activity is slightly higher in the human lineage, relative to the chimpanzee lineage, and that L1s have experienced different evolutionary fates in these two lineages, resulting from random variation or competition between L1 subfamily lineages. Next, we analyzed the magnitude of Alu recombination-mediated deletions (ARMDs) in the chimpanzee lineage subsequent to the human-chimpanzee divergence (~6 million years ago). We have identified 663 chimpanzee lineage-specific deletions (involving a total of ~771 kb of genomic sequence) attributable to this process. The RefSeq databases indicate that 13 exons in six genes are annotated as either demonstrably or putatively functional in the human genome, and 299 intronic regions have been deleted through ARMDs in the chimpanzee lineage. In the third analysis, we characterize chromosomal inversion events between the human and chimpanzee genomes caused by inverted L1-L1 or Alu-Alu pairs. We have identified 49 retrotransposon recombination-mediated inversion (RRMI) loci and, among them, three RRMI loci contain inverted exonic regions in known genes. Therefore, we suggest that L1 and Alu elements have contributed to the genomic and phenotypic diversity between humans and chimpanzees since the divergence of the two species