Dosage sensitivity shapes the evolution of copy-number varied regions
Dosage sensitivity is an important evolutionary force which impacts on gene dispensability and duplicability. The newly available data on human copy-number variation (CNV) allow an analysis of the most recent and ongoing evolution. Provided that heterozygous gene deletions and duplications actually...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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Public Library of Science
2010
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| _version_ | 1797098256155541504 |
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| author | Schuster-Böckler, B Conrad, D Bateman, A |
| author_facet | Schuster-Böckler, B Conrad, D Bateman, A |
| author_sort | Schuster-Böckler, B |
| collection | OXFORD |
| description | Dosage sensitivity is an important evolutionary force which impacts on gene dispensability and duplicability. The newly available data on human copy-number variation (CNV) allow an analysis of the most recent and ongoing evolution. Provided that heterozygous gene deletions and duplications actually change gene dosage, we expect to observe negative selection against CNVs encompassing dosage sensitive genes. In this study, we make use of several sources of population genetic data to identify selection on structural variations of dosage sensitive genes. We show that CNVs can directly affect expression levels of contained genes. We find that genes encoding members of protein complexes exhibit limited expression variation and overlap significantly with a manually derived set of dosage sensitive genes. We show that complexes and other dosage sensitive genes are underrepresented in CNV regions, with a particular bias against frequent variations and duplications. These results suggest that dosage sensitivity is a significant force of negative selection on regions of copy-number variation. |
| first_indexed | 2024-03-07T05:06:56Z |
| format | Journal article |
| id | oxford-uuid:da4099be-9d1e-46a3-b43e-4104c434ef97 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:06:56Z |
| publishDate | 2010 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:da4099be-9d1e-46a3-b43e-4104c434ef972022-03-27T09:01:50ZDosage sensitivity shapes the evolution of copy-number varied regionsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:da4099be-9d1e-46a3-b43e-4104c434ef97EnglishSymplectic Elements at OxfordPublic Library of Science2010Schuster-Böckler, BConrad, DBateman, ADosage sensitivity is an important evolutionary force which impacts on gene dispensability and duplicability. The newly available data on human copy-number variation (CNV) allow an analysis of the most recent and ongoing evolution. Provided that heterozygous gene deletions and duplications actually change gene dosage, we expect to observe negative selection against CNVs encompassing dosage sensitive genes. In this study, we make use of several sources of population genetic data to identify selection on structural variations of dosage sensitive genes. We show that CNVs can directly affect expression levels of contained genes. We find that genes encoding members of protein complexes exhibit limited expression variation and overlap significantly with a manually derived set of dosage sensitive genes. We show that complexes and other dosage sensitive genes are underrepresented in CNV regions, with a particular bias against frequent variations and duplications. These results suggest that dosage sensitivity is a significant force of negative selection on regions of copy-number variation. |
| spellingShingle | Schuster-Böckler, B Conrad, D Bateman, A Dosage sensitivity shapes the evolution of copy-number varied regions |
| title | Dosage sensitivity shapes the evolution of copy-number varied regions |
| title_full | Dosage sensitivity shapes the evolution of copy-number varied regions |
| title_fullStr | Dosage sensitivity shapes the evolution of copy-number varied regions |
| title_full_unstemmed | Dosage sensitivity shapes the evolution of copy-number varied regions |
| title_short | Dosage sensitivity shapes the evolution of copy-number varied regions |
| title_sort | dosage sensitivity shapes the evolution of copy number varied regions |
| work_keys_str_mv | AT schusterbocklerb dosagesensitivityshapestheevolutionofcopynumbervariedregions AT conradd dosagesensitivityshapestheevolutionofcopynumbervariedregions AT batemana dosagesensitivityshapestheevolutionofcopynumbervariedregions |