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Global comparison of the human and chimpanzee transcriptomes using Affymetrix exon arrays
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Genomics. (Gyllensten)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Genomics. (Gyllensten)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Genomics. (Feuk)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Genomics. (Gyllensten)
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

We have used high-density exon arrays to study the human and chimpanzee transcriptome in cerebellum, heart and liver excluding probesets with mismatches to the chimpanzee. A total of 6281 RefSeq genes were expressed in our samples, the majority being expressed in two or more tissues, while ~ 6 % lacked expression in one of the species. A total of 923 RefSeq genes showed differences in expression between human and chimpanzes. More genes were differentially expressed in cerebellum (8.4 %) than in liver (6.9 %) and heart (4.5 %). Genes showing differential expression between species to a large extent also showed strong tissue-specific expression within species. Of the differentially expressed genes, more were upregulated in human versus chimpanzee, than the other way around. Liver had the highest proportion of genes with spliced genes (50 %), followed by cerebellum (40 %) and heart (30 %). Differentially expressed genes were often detected also as spliced (66-78 %). As one type of splice variation, we identified 26 genes with cassette exons, i.e. the exon is only included in one species. Cassette exon usage was tissue specific to a large extent and for the majority of cassette exons we observed expression in both human and chimpanzee in the other tissues. Taken together, our results indicate that splicing differences represents an extensive and important source of variation between species.

Keyword [en]
chimpanzee human transcriptome comparison
National Category
Medical Genetics
Research subject
Bioinformatics
Identifiers
URN: urn:nbn:se:uu:diva-113576OAI: oai:DiVA.org:uu-113576DiVA: diva2:291181
Available from: 2010-01-30 Created: 2010-01-30 Last updated: 2010-02-02
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.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 522
Keyword
human, chimpanzee, genome, transcriptome, comparative studies, exon arrays, next-generation sequencing, premature termination codon, alternative splicing, primate evolution
National Category
Medical Genetics
Research subject
Bioinformatics
Identifiers
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)
Opponent
Supervisors
Available from: 2010-03-02 Created: 2010-01-21 Last updated: 2010-03-02Bibliographically approved

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Wetterbom, Anna

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