On the Expansion of “Dangerous” Gene Repertoires by Whole-Genome Duplications in Early Vertebrates
The emergence and evolutionary expansion of gene families implicated in cancers and other severe genetic diseases is an evolutionary oddity from a natural selection perspective. Here, we show that gene families prone to deleterious mutations in the human genome have been preferentially expanded by t...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2012-11-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124712003658 |
| _version_ | 1818525460803354624 |
|---|---|
| author | Param Priya Singh Séverine Affeldt Ilaria Cascone Rasim Selimoglu Jacques Camonis Hervé Isambert |
| author_facet | Param Priya Singh Séverine Affeldt Ilaria Cascone Rasim Selimoglu Jacques Camonis Hervé Isambert |
| author_sort | Param Priya Singh |
| collection | DOAJ |
| description | The emergence and evolutionary expansion of gene families implicated in cancers and other severe genetic diseases is an evolutionary oddity from a natural selection perspective. Here, we show that gene families prone to deleterious mutations in the human genome have been preferentially expanded by the retention of “ohnolog” genes from two rounds of whole-genome duplication (WGD) dating back from the onset of jawed vertebrates. We further demonstrate that the retention of many ohnologs suspected to be dosage balanced is in fact indirectly mediated by their susceptibility to deleterious mutations. This enhanced retention of “dangerous” ohnologs, defined as prone to autosomal-dominant deleterious mutations, is shown to be a consequence of WGD-induced speciation and the ensuing purifying selection in post-WGD species. These findings highlight the importance of WGD-induced nonadaptive selection for the emergence of vertebrate complexity, while rationalizing, from an evolutionary perspective, the expansion of gene families frequently implicated in genetic disorders and cancers. |
| first_indexed | 2024-12-11T06:09:31Z |
| format | Article |
| id | doaj.art-496e318935404bb68de2bd1988285ed1 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T06:09:31Z |
| publishDate | 2012-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-496e318935404bb68de2bd1988285ed12022-12-22T01:18:11ZengElsevierCell Reports2211-12472012-11-01251387139810.1016/j.celrep.2012.09.034On the Expansion of “Dangerous” Gene Repertoires by Whole-Genome Duplications in Early VertebratesParam Priya Singh0Séverine Affeldt1Ilaria Cascone2Rasim Selimoglu3Jacques Camonis4Hervé Isambert5CNRS UMR168, UPMC, Institut Curie, Research Center, 26, rue d’Ulm, 75248 Paris, FranceCNRS UMR168, UPMC, Institut Curie, Research Center, 26, rue d’Ulm, 75248 Paris, FranceINSERM U830, UPMC, Institut Curie, Research Center, 26, rue d’Ulm, 75248 Paris, FranceINSERM U830, UPMC, Institut Curie, Research Center, 26, rue d’Ulm, 75248 Paris, FranceINSERM U830, UPMC, Institut Curie, Research Center, 26, rue d’Ulm, 75248 Paris, FranceCNRS UMR168, UPMC, Institut Curie, Research Center, 26, rue d’Ulm, 75248 Paris, FranceThe emergence and evolutionary expansion of gene families implicated in cancers and other severe genetic diseases is an evolutionary oddity from a natural selection perspective. Here, we show that gene families prone to deleterious mutations in the human genome have been preferentially expanded by the retention of “ohnolog” genes from two rounds of whole-genome duplication (WGD) dating back from the onset of jawed vertebrates. We further demonstrate that the retention of many ohnologs suspected to be dosage balanced is in fact indirectly mediated by their susceptibility to deleterious mutations. This enhanced retention of “dangerous” ohnologs, defined as prone to autosomal-dominant deleterious mutations, is shown to be a consequence of WGD-induced speciation and the ensuing purifying selection in post-WGD species. These findings highlight the importance of WGD-induced nonadaptive selection for the emergence of vertebrate complexity, while rationalizing, from an evolutionary perspective, the expansion of gene families frequently implicated in genetic disorders and cancers.http://www.sciencedirect.com/science/article/pii/S2211124712003658 |
| spellingShingle | Param Priya Singh Séverine Affeldt Ilaria Cascone Rasim Selimoglu Jacques Camonis Hervé Isambert On the Expansion of “Dangerous” Gene Repertoires by Whole-Genome Duplications in Early Vertebrates Cell Reports |
| title | On the Expansion of “Dangerous” Gene Repertoires by Whole-Genome Duplications in Early Vertebrates |
| title_full | On the Expansion of “Dangerous” Gene Repertoires by Whole-Genome Duplications in Early Vertebrates |
| title_fullStr | On the Expansion of “Dangerous” Gene Repertoires by Whole-Genome Duplications in Early Vertebrates |
| title_full_unstemmed | On the Expansion of “Dangerous” Gene Repertoires by Whole-Genome Duplications in Early Vertebrates |
| title_short | On the Expansion of “Dangerous” Gene Repertoires by Whole-Genome Duplications in Early Vertebrates |
| title_sort | on the expansion of dangerous gene repertoires by whole genome duplications in early vertebrates |
| url | http://www.sciencedirect.com/science/article/pii/S2211124712003658 |
| work_keys_str_mv | AT parampriyasingh ontheexpansionofdangerousgenerepertoiresbywholegenomeduplicationsinearlyvertebrates AT severineaffeldt ontheexpansionofdangerousgenerepertoiresbywholegenomeduplicationsinearlyvertebrates AT ilariacascone ontheexpansionofdangerousgenerepertoiresbywholegenomeduplicationsinearlyvertebrates AT rasimselimoglu ontheexpansionofdangerousgenerepertoiresbywholegenomeduplicationsinearlyvertebrates AT jacquescamonis ontheexpansionofdangerousgenerepertoiresbywholegenomeduplicationsinearlyvertebrates AT herveisambert ontheexpansionofdangerousgenerepertoiresbywholegenomeduplicationsinearlyvertebrates |