Comparative Genomic Analysis of Human and Chimpanzee Indicates a Key Role for Indels in Primate Evolution

Abstract

Sequence comparison of humans and chimpanzees is of interest to understand the mechanisms behind primate evolution. Here we present an independent analysis of human chromosome 21 and the high-quality BAC clone sequences of the homologous chimpanzee chromosome 22. In contrast to previous studies, we have used global alignment methods and Ensembl predictions of protein coding genes (n = 224) for the analysis. Divergence due to insertions and deletions (indels) along with substitutions was examined separately for different genomic features (coding, noncoding genic, and intergenic sequence). The major part of the genomic divergence could be attributed to indels (5.07%), while the nucleotide divergence was estimated as 1.52%. Thus the total divergence was estimated as 6.58%. When excluding repeats and low-complexity DNA the total divergence decreased to 2.37%. The chromosomal distribution of nucleotide substitutions and indel events was significantly correlated. To further examine the role of indels in primate evolution we focused on coding sequences. Indels were found within the coding sequence of 13% of the genes and approximately half of the indels have not been reported previously. In 5% of the chimpanzee genes, indels or substitutions caused premature stop codons that rendered the affected transcripts nonfunctional. Taken together, our findings demonstrate that indels comprise the majority of the genomic divergence. Furthermore, indels occur frequently in coding sequences. Our results thereby support the hypothesis that indels may have a key role in primate evolution.

Impact of Endogenous Intronic Retroviruses on Major Histocompatibility Complex Class II Diversity and Stability

“…However, indels seem to be responsible for more than 3% of the differences (71). Thus, the overall divergence between the chimpanzee and human genomes is closer to 4% (74,75). In this respect, the retroviral insertion shared by the DRB2 and DRB6 pseudogenes behaves as expected and displays lower similarity values.…”

Sequence shortening in the rodent ancestor

“…Short insertions and deletions (indels) account for a significant amount of the variation in mammalian genomes and are likely to make an important contribution to species-specific traits (Britten 2002;Wetterbom et al 2006). Their importance for medical genetics is highlighted by the fact that they have been implicated in a wide range of human diseases, the archetypal example being the phenylalanine deletion at position 508 in the CFTR protein that results in cystic fibrosis (Riordan et al 1989).…”

A framework for incorporating evolutionary genomics into biodiversity conservation and management

“…Whilst SNPs are informative and relatively easy to identify, studies on model species have shown that insertion-deletion polymorphisms (indels) also play an important role in genome evolution and adaptation [73][74][75][76]. Identifying indels from high-throughput sequencing data remains a difficult bioinformatic problem [77], and identifying large indels in RRS data is especially difficult because only a small percentage of the genome is sequenced.…”