Loss and gain of function in SERPINB11: an example of a gene under selection on standing variation, with implications for host-pathogen interactions.
Serine protease inhibitors (SERPINs) are crucial in the regulation of diverse biological processes including inflammation and immune response. SERPINB11, located in the 18q21 gene cluster, is a polymorphic gene/pseudogene coding for a non-inhibitory SERPIN. In a genome-wide scan for recent selection...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3290568?pdf=render |
| _version_ | 1819162152440692736 |
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| author | Susana Seixas Nevyana Ivanova Zelia Ferreira Jorge Rocha Bruno L Victor |
| author_facet | Susana Seixas Nevyana Ivanova Zelia Ferreira Jorge Rocha Bruno L Victor |
| author_sort | Susana Seixas |
| collection | DOAJ |
| description | Serine protease inhibitors (SERPINs) are crucial in the regulation of diverse biological processes including inflammation and immune response. SERPINB11, located in the 18q21 gene cluster, is a polymorphic gene/pseudogene coding for a non-inhibitory SERPIN. In a genome-wide scan for recent selection, SERPINB11 was identified as a potential candidate gene for adaptive evolution in Yoruba. The present study sought a better understanding of the evolutionary history of SERPINB11, with special focus on evaluating its selective signature. Through the resequencing of coding and noncoding regions of SERPINB11 in 20 Yorubans and analyzing primate orthologous sequences, we identified a full-length SERPINB11 variant encoding a non-inhibitory SERPIN as the putative candidate of selection--probably driven to higher frequencies by an adaptive response using preexisting variation. In addition, we detected contrasting evolutionary features of SERPINB11 in primates: While primate phylogeny as a whole is under purifying selection, the human lineage shows evidence of positive selection in a few codons, all associated with the active SERPINB11. Comparative modeling studies suggest that positively selected codons reduce SERPINB11's ability to undergo the conformational changes typical of inhibitory SERPINs--suggesting that it is evolving towards a new non-inhibitory function in humans. Significant correlations between SERPINB11 variants and the environmental variables, pastoralism and pathogen richness, have led us to propose a selective advantage through host-pathogen interactions, possibly linked to an adaptive response combating the emergence of infectious diseases in recent human evolution. This work represents the first description of a resurrected gene in humans, and may well exemplify selection on standing variation triggered by drastic ecological shifts. |
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| id | doaj.art-ef0a2baaf48f40fbb28bf7fde9d441fc |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T17:23:42Z |
| publishDate | 2012-01-01 |
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| series | PLoS ONE |
| spelling | doaj.art-ef0a2baaf48f40fbb28bf7fde9d441fc2022-12-21T18:18:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0172e3251810.1371/journal.pone.0032518Loss and gain of function in SERPINB11: an example of a gene under selection on standing variation, with implications for host-pathogen interactions.Susana SeixasNevyana IvanovaZelia FerreiraJorge RochaBruno L VictorSerine protease inhibitors (SERPINs) are crucial in the regulation of diverse biological processes including inflammation and immune response. SERPINB11, located in the 18q21 gene cluster, is a polymorphic gene/pseudogene coding for a non-inhibitory SERPIN. In a genome-wide scan for recent selection, SERPINB11 was identified as a potential candidate gene for adaptive evolution in Yoruba. The present study sought a better understanding of the evolutionary history of SERPINB11, with special focus on evaluating its selective signature. Through the resequencing of coding and noncoding regions of SERPINB11 in 20 Yorubans and analyzing primate orthologous sequences, we identified a full-length SERPINB11 variant encoding a non-inhibitory SERPIN as the putative candidate of selection--probably driven to higher frequencies by an adaptive response using preexisting variation. In addition, we detected contrasting evolutionary features of SERPINB11 in primates: While primate phylogeny as a whole is under purifying selection, the human lineage shows evidence of positive selection in a few codons, all associated with the active SERPINB11. Comparative modeling studies suggest that positively selected codons reduce SERPINB11's ability to undergo the conformational changes typical of inhibitory SERPINs--suggesting that it is evolving towards a new non-inhibitory function in humans. Significant correlations between SERPINB11 variants and the environmental variables, pastoralism and pathogen richness, have led us to propose a selective advantage through host-pathogen interactions, possibly linked to an adaptive response combating the emergence of infectious diseases in recent human evolution. This work represents the first description of a resurrected gene in humans, and may well exemplify selection on standing variation triggered by drastic ecological shifts.http://europepmc.org/articles/PMC3290568?pdf=render |
| spellingShingle | Susana Seixas Nevyana Ivanova Zelia Ferreira Jorge Rocha Bruno L Victor Loss and gain of function in SERPINB11: an example of a gene under selection on standing variation, with implications for host-pathogen interactions. PLoS ONE |
| title | Loss and gain of function in SERPINB11: an example of a gene under selection on standing variation, with implications for host-pathogen interactions. |
| title_full | Loss and gain of function in SERPINB11: an example of a gene under selection on standing variation, with implications for host-pathogen interactions. |
| title_fullStr | Loss and gain of function in SERPINB11: an example of a gene under selection on standing variation, with implications for host-pathogen interactions. |
| title_full_unstemmed | Loss and gain of function in SERPINB11: an example of a gene under selection on standing variation, with implications for host-pathogen interactions. |
| title_short | Loss and gain of function in SERPINB11: an example of a gene under selection on standing variation, with implications for host-pathogen interactions. |
| title_sort | loss and gain of function in serpinb11 an example of a gene under selection on standing variation with implications for host pathogen interactions |
| url | http://europepmc.org/articles/PMC3290568?pdf=render |
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