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Comparative genomic analysis of human and chimpanzee indicates a key role for indels in primate evolution
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
2006 (English)In: Journal of Molecular Evolution, ISSN 0022-2844, E-ISSN 1432-1432, Vol. 63, no 5, 682-690 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2006. Vol. 63, no 5, 682-690 p.
Keyword [en]
indels, comparative genomics, chimpanzee, primate evolution
National Category
URN: urn:nbn:se:uu:diva-10256DOI: 10.1007/s00239-006-0045-7ISI: 000242014800010PubMedID: 17075697OAI: oai:DiVA.org:uu-10256DiVA: diva2:38024
Available from: 2007-04-20 Created: 2007-04-20 Last updated: 2011-05-12Bibliographically approved
In thesis
1. Genome and Transcriptome Comparisons between Human and Chimpanzee
Open this publication in new window or tab >>Genome and Transcriptome Comparisons between Human and Chimpanzee
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The chimpanzee is humankind’s closest living relative and the two species diverged ~6 million years ago. Comparative studies of the human and chimpanzee genomes and transcriptomes are of great interest to understand the molecular mechanisms of speciation and the development of species-specific traits.

The aim of this thesis is to characterize differences between the two species with regard to their genome sequences and the resulting transcript profiles. The first two papers focus on indel divergence and in particular, indels causing premature termination codons (PTCs) in 8% of the chimpanzee genes. The density of PTC genes is correlated with both the distance to the telomere and the indel divergence. Many PTC genes have several associated transcripts and since not all are affected by the PTC we propose that PTCs may affect the pattern of expressed isoforms. In the third paper, we investigate the transcriptome divergence in cerebellum, heart and liver, using high-density exon arrays. The results show that gene expression differs more between tissues than between species. Approximately 15% of the genes are differentially expressed between species, and half of the genes show different splicing patterns. We identify 28 cassette exons which are only included in one of the species, often in a tissue-specific manner. In the fourth paper, we use massive parallel sequencing to study the chimpanzee transcriptome in frontal cortex and liver. We estimate gene expression and search for novel transcribed regions (TRs). The majority of TRs are located close to genes and possibly extend the annotations. A subset of TRs are not found in the human genome. The brain transcriptome differs substantially from that of the liver and we identify a subset of genes enriched with TRs in frontal cortex.

In conclusion, this thesis provides evidence of extensive genomic and transcriptomic variability between human and chimpanzee. The findings provide a basis for further studies of the underlying differences affecting phenotypic divergence between human and chimpanzee.




Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 61 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 522
human, chimpanzee, genome, transcriptome, comparative studies, exon arrays, next-generation sequencing, premature termination codon, alternative splicing, primate evolution
National Category
Medical Genetics
Research subject
urn:nbn:se:uu:diva-112893 (URN)978-91-554-7720-2 (ISBN)
Public defence
2010-03-24, Rudbeck Hall, Rudbeck laboratory, SE-751 85 Uppsala, Uppsala, 09:00 (English)
Available from: 2010-03-02 Created: 2010-01-21 Last updated: 2010-03-02Bibliographically approved

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