Regulatory Divergence of Transcript Isoforms in a Mammalian Model System.
Phenotypic differences between species are driven by changes in gene expression and, by extension, by modifications in the regulation of the transcriptome. Investigation of mammalian transcriptome divergence has been restricted to analysis of bulk gene expression levels and gene-internal splicing. U...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0137367 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849726570210525184 |
|---|---|
| author | Sarah Leigh-Brown Angela Goncalves David Thybert Klara Stefflova Stephen Watt Paul Flicek Alvis Brazma John C Marioni Duncan T Odom |
| author_facet | Sarah Leigh-Brown Angela Goncalves David Thybert Klara Stefflova Stephen Watt Paul Flicek Alvis Brazma John C Marioni Duncan T Odom |
| author_sort | Sarah Leigh-Brown |
| collection | DOAJ |
| description | Phenotypic differences between species are driven by changes in gene expression and, by extension, by modifications in the regulation of the transcriptome. Investigation of mammalian transcriptome divergence has been restricted to analysis of bulk gene expression levels and gene-internal splicing. Using allele-specific expression analysis in inter-strain hybrids of Mus musculus, we determined the contribution of multiple cellular regulatory systems to transcriptome divergence, including: alternative promoter usage, transcription start site selection, cassette exon usage, alternative last exon usage, and alternative polyadenylation site choice. Between mouse strains, a fifth of genes have variations in isoform usage that contribute to transcriptomic changes, half of which alter encoded amino acid sequence. Virtually all divergence in isoform usage altered the post-transcriptional regulatory instructions in gene UTRs. Furthermore, most genes with isoform differences between strains contain changes originating from multiple regulatory systems. This result indicates widespread cross-talk and coordination exists among different regulatory systems. Overall, isoform usage diverges in parallel with and independently to gene expression evolution, and the cis and trans regulatory contribution to each differs significantly. |
| format | Article |
| id | doaj-art-d8a1019b5ad84ccbbf80157fe88db89a |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-d8a1019b5ad84ccbbf80157fe88db89a2025-08-20T03:10:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01109e013736710.1371/journal.pone.0137367Regulatory Divergence of Transcript Isoforms in a Mammalian Model System.Sarah Leigh-BrownAngela GoncalvesDavid ThybertKlara StefflovaStephen WattPaul FlicekAlvis BrazmaJohn C MarioniDuncan T OdomPhenotypic differences between species are driven by changes in gene expression and, by extension, by modifications in the regulation of the transcriptome. Investigation of mammalian transcriptome divergence has been restricted to analysis of bulk gene expression levels and gene-internal splicing. Using allele-specific expression analysis in inter-strain hybrids of Mus musculus, we determined the contribution of multiple cellular regulatory systems to transcriptome divergence, including: alternative promoter usage, transcription start site selection, cassette exon usage, alternative last exon usage, and alternative polyadenylation site choice. Between mouse strains, a fifth of genes have variations in isoform usage that contribute to transcriptomic changes, half of which alter encoded amino acid sequence. Virtually all divergence in isoform usage altered the post-transcriptional regulatory instructions in gene UTRs. Furthermore, most genes with isoform differences between strains contain changes originating from multiple regulatory systems. This result indicates widespread cross-talk and coordination exists among different regulatory systems. Overall, isoform usage diverges in parallel with and independently to gene expression evolution, and the cis and trans regulatory contribution to each differs significantly.https://doi.org/10.1371/journal.pone.0137367 |
| spellingShingle | Sarah Leigh-Brown Angela Goncalves David Thybert Klara Stefflova Stephen Watt Paul Flicek Alvis Brazma John C Marioni Duncan T Odom Regulatory Divergence of Transcript Isoforms in a Mammalian Model System. PLoS ONE |
| title | Regulatory Divergence of Transcript Isoforms in a Mammalian Model System. |
| title_full | Regulatory Divergence of Transcript Isoforms in a Mammalian Model System. |
| title_fullStr | Regulatory Divergence of Transcript Isoforms in a Mammalian Model System. |
| title_full_unstemmed | Regulatory Divergence of Transcript Isoforms in a Mammalian Model System. |
| title_short | Regulatory Divergence of Transcript Isoforms in a Mammalian Model System. |
| title_sort | regulatory divergence of transcript isoforms in a mammalian model system |
| url | https://doi.org/10.1371/journal.pone.0137367 |
| work_keys_str_mv | AT sarahleighbrown regulatorydivergenceoftranscriptisoformsinamammalianmodelsystem AT angelagoncalves regulatorydivergenceoftranscriptisoformsinamammalianmodelsystem AT davidthybert regulatorydivergenceoftranscriptisoformsinamammalianmodelsystem AT klarastefflova regulatorydivergenceoftranscriptisoformsinamammalianmodelsystem AT stephenwatt regulatorydivergenceoftranscriptisoformsinamammalianmodelsystem AT paulflicek regulatorydivergenceoftranscriptisoformsinamammalianmodelsystem AT alvisbrazma regulatorydivergenceoftranscriptisoformsinamammalianmodelsystem AT johncmarioni regulatorydivergenceoftranscriptisoformsinamammalianmodelsystem AT duncantodom regulatorydivergenceoftranscriptisoformsinamammalianmodelsystem |