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Genome-wide analysis of chimpanzee genes with premature termination codons
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.
2009 (English)In: BMC Genomics, ISSN 1471-2164, Vol. 10, 56- p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Premature termination codons (PTCs) cause mRNA degradation or a truncated protein and thereby contribute to the transcriptome and proteome divergence between species. Here we present the first genome-wide study of PTCs in the chimpanzee. By comparing the human and chimpanzee genome sequences we identify and characterize genes with PTCs, in order to understand the contribution of these mutations to the transcriptome diversity between the species. RESULTS: We have studied a total of 13,487 human-chimpanzee gene pairs and found that ~8% were affected by PTCs in the chimpanzee. A majority (764/1,109) of PTCs were caused by insertions or deletions and the remaining part was caused by substitutions. The distribution of PTC genes varied between chromosomes, with Y having the highest proportion. Furthermore, the density of PTC genes varied on a megabasepair scale within chromosomes and we found the density to be correlated both with indel divergence and proximity to the telomere. Within genes, PTCs were more common close to the 5' and 3' ends of the amino acid sequence. Gene Ontology classification revealed that olfactory receptor genes were over represented among the PTC genes. CONCLUSION: Our results showed that the density of PTC genes fluctuated across the genome depending on the local genomic context. PTCs were preferentially located in the terminal parts of the transcript, which generally have a lower frequency of functional domains, indicating that selection was operating against PTCs at sites central to protein function. The enrichment of GO terms associated with olfaction suggests that PTCs may have influenced the difference in the repertoire of olfactory genes between humans and chimpanzees. In summary, 8% of the chimpanzee genes were affected by PTCs and this type of variation is likely to have an important effect on the transcript and proteomic divergence between humans and chimpanzees.

Place, publisher, year, edition, pages
2009. Vol. 10, 56- p.
Keyword [en]
cervical carcinoma, HLA, HPV 16 E6
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-102555DOI: 10.1186/1471-2164-10-56ISI: 000264122500002PubMedID: 19178713OAI: oai:DiVA.org:uu-102555DiVA: diva2:216354
Available from: 2009-05-08 Created: 2009-05-08 Last updated: 2011-03-09Bibliographically 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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