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PMID: 16432206 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S.

Genomic fossils as a snapshot of the human transcriptome.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 103 ·No. 5 ·2006-01-31 ·Pages 1364-9

Shemesh R, Novik A, Edelheit S, Sorek R

Abstract

Processed pseudogenes (PPGs) are cDNA sequences that were generated through reverse transcription of mature, spliced mRNAs and have subsequently been reinserted at a new genomic location. These cDNA sequences are usually no longer transcribed and are considered "dead on arrival." Here we show that PPGs can be used to generate a map of the transcriptome. By analyzing thousands of human PPGs, we were able to discover hundreds of transcript variants so far unidentified. An experimental verification of a subset of these variants by RT-PCR indicates that most of them are still active in the human transcriptome. Furthermore, we demonstrate that PPGs can enable the identification of ancient splice variants that were expressed ancestrally but are now extinct. Our results show that the genome itself carries a "virtual cDNA library" that can readily be used to analyze both present and ancestral transcripts. Our approach can be applied to sequenced metazoan genomes to computationally annotate splicing variation even when expressed sequences are unavailable.

MeSH Terms
Alternative Splicing Base Sequence DNA, Complementary/metabolism Exons Expressed Sequence Tags Fossils Gene Library Genome Genome, Human Humans Models, Genetic Molecular Sequence Data Phylogeny Polymerase Chain Reaction Pseudogenes RNA, Messenger/metabolism Reverse Transcriptase Polymerase Chain Reaction Software Tissue Distribution Transcription, Genetic
Chemicals
DNA, Complementary RNA, Messenger
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Shemesh Ronen
Compugen Ltd., 72 Pinchas Rosen Street, Tel Aviv 69512, Israel.
Novik Amit
Edelheit Sarit
Sorek Rotem
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0509330103
Published
2006-01-31
Epub
2006-00-23
Pages
1364-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1360558
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0509330103 PMC Full Text View journal details
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