Comparative Genomic Analysis of Human and Chimpanzee Indicates a Key Role for Indels in Primate Evolution
- 366 Downloads
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.
KeywordsIndels Comparative genomics Chimpanzee Primate evolution
We wish to thank The International Chimpanzee Chromosome 22 Consortium for providing the chimpanzee BAC sequences, Ronald Bontrop for providing chimpanzee cell lines, and Bengt-Olle Röken for providing the gorilla sample. We would also like to thank Ulf Gyllensten for valuable comments on the manuscript and Charlotte Johansson for excellent technical assistance. This work was supported by grants from the Graduate Research School in Genomics and Bioinformatics, the Swedish Research Council, the Erik Philip-Sörensen Foundation, the Beijer Foundation, the Marcus Borgström Foundation, and the Magnus Bergvalls Foundation.
- Anzai T, Shiina T, Kimura N, Yanagiya K, Kohara S, Shigenari A, Yamagata T, Kulski JK, Naruse TK, Fujimori Y, Fukuzumi Y, Yamazaki M, Tashiro H, Iwarmoto C, Umehara Y, Imardshi T, Meyer A, Ikeo K, Gojobori T, Bahram S, Inoko H (2003) Comparative sequencing of human and chimpanzee MHC class I regions unveils insertions/deletions as the major path to genomic divergence. Proc Natl Acad Sci USA 100:7708–7713PubMedCrossRefGoogle Scholar
- Birney E, Andrews D, Bevan P, Caccamo M, Cameron G, Chen Y, Clarke L, Coates G, Cox T, Cuff J, Curwen V, Cutts T, Down T, Durbin R, Eyras E, Fernandez-Suarez XM, Gane P, Gibbins B, Gilbert J, Hammond M, Hotz H, lyer V, Ka-hari A, Jekosch K, Kasprzyk A, Keefe D, Keenan S, Lehvaslaiho H, McVicker G, Melsopp C, Meidl P, Mongin E, Pettett R, Potter S, Proctor G, Rae M, Searle S, Slater G, Smedley D, Smith J, Spooner W, Stabenau A, Stalker J, Storey R, Ureta-Vidal A, Woodwark C, Clamp M, Hubbard T (2004a) Ensembl 2004. Nucleic Acids Res 32 (Database Issue):D468–D470CrossRefGoogle Scholar
- Choi DK, Suzuki Y, Yoshimura S, Togashi T, Hida M, Taylor TD, Wang Y, Sugano S, Hattori M, Sakaki Y (2001) Molecular cloning and characterization of a gene expressed in mouse developing tongue, mDscr5 gene, a homolog of human DSCR5 (Down syndrome Critical Region gene 5). Mamm Genome 12:347–351PubMedCrossRefGoogle Scholar
- Hardison RC, Roskin KM, Yang S, Dieklians M, Kent WJ, Weber R, Elnitski L, Li J, O’Connor M, Kolbe D, Schwartz S, Furey TS, Whelan S, Goldman N, Smit A, Miller W, Chiaromonte F, Haussler D (2003) Covariation in frequencies of substitution, deletion, transposition, and recombination during eutherian evolution. Genome Res 13:13–26PubMedCrossRefGoogle Scholar
- Klucken J, Buchler C, Orso E, Kaminski WE, Porsch-Ozcurumez M, Liebisch G, Kapinsky M, Diederich W, Drobnik W, Dean M, Allikmets R, Schmitz G (2000) ABCG1 (ABC8), the human homolog of the Drosophila white gene, is a regulator of macrophage cholesterol and phospholipid transport. Proc Natl Acad Sci USA 97:817–822PubMedCrossRefGoogle Scholar
- Smit AFA, Green P (2006) http://repeatmasker.org
- Watanabe H, Fujiyama A, Hattori M, Taylor TD, Toyoda A, Kuroki Y, Noguchi H, BenKahla A, Lehrach H, Sudbrak R, Kube M, Taenzer S, Galgoczy P, Platzer M, Scharfe M, Nordsiek G, Blocker H, Hellmann I, Khaitovich P, Paabo S, Reinhardt R, Zheng HJ, Zhang XL, Zhu GF, Wang BF, Fu G, Ren SX, Zhao GP, Chen Z, Lee YS, Cheong JE, Choi SH, Wu KM, Liu TT, Hsiao KJ, Tsai SF, Kim CG, S OO, Kitano T, Kohara Y, Saitou N, Park HS, Wang SY, Yaspo ML, Sakaki Y (2004) DNA sequence and comparative analysis of chimpanzee chromosome 22. Nature 429:382–388PubMedCrossRefGoogle Scholar
- Zhu Y, Xu G, Patel A, McLaughlin MM, Silverman C, Knecht K, Sweitzer S, Li X, McDonnell P, Mirabile R, Zimmerman D, Boyce R, Tierney LA, Hu E, Livi GP, Wolf B, Abdel-Meguid SS, Rose GD, Aurora R, Hensley P, Briggs M, Young PR (2002) Cloning, expression, and initial characterization of a novel cytokine-like gene family. Genomics 80:144–150PubMedCrossRefGoogle Scholar