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Deep sequencing of the chimpanzee transcriptome identifies numerous novel transcribed regions in frontal cortex and liver
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 performed the first global profiling of the chimpanzee transcriptome by using deep sequencing of cDNA from brain and liver. This enabled us to quantify expression of RefSeq transcripts, identify novel transcribed regions with no previous annotations in databases and additionally search for transcribed regions with no support in the human genome.

Using stringent criteria for transcription, we identified 9,061 expressed RefSeq transcripts and 5,532 novel transcribed regions., of which the vast majority were found intronically in RefSeq transcripts and ~ 15 % mapped intergenically. In addition,  a little less than 150 novel transcribed regions in the chimpanzee appeared to be absent from the human reference sequence. Novel transcribed regions may represent new coding regions, untranslated regions unspliced mRNAs or diferent types of non-coding transcripts. The transcriptional profile of the brain stands out in several ways: a higher number of RefSeq transcripts were expressed in brain than in liver and novel transcribed regions were also more abundant in brain. Furthermore, we identified an interesting subset of RefSeq genes with a high density of novel transcribed regions scattered across the introns. These genes clustered in central pathways of the nervous system, with an overrepresentation of genes acting in the synapse and many of which have been associated to cognitive disorders in the human.

Our results support the prevailing view of wide-spread transcription in mammalian genomes and further highlight the vast, mostly uncharacterized, transcript variability in the primate brain.

 

Keyword [en]
chimpanzee, transcriptome profiling, deep sequencing
National Category
Medical Genetics
Research subject
Bioinformatics
Identifiers
URN: urn:nbn:se:uu:diva-113577OAI: oai:DiVA.org:uu-113577DiVA: diva2:291182
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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