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Recurrent bottlenecks in the malaria life cycle obscure signals of positive selection
Detecting signals of selection in the genome of malaria parasites is a key to identify targets for drug and vaccine development. Malaria parasites have a unique life cycle alternating between vector and host organism with a population bottleneck at each transition. These recurrent bottlenecks could...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cambridge University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139472/ https://www.ncbi.nlm.nih.gov/pubmed/24560397 http://dx.doi.org/10.1017/S0031182014000067 |
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author | CHANG, HSIAO-HAN HARTL, DANIEL L. |
author_facet | CHANG, HSIAO-HAN HARTL, DANIEL L. |
author_sort | CHANG, HSIAO-HAN |
collection | PubMed |
description | Detecting signals of selection in the genome of malaria parasites is a key to identify targets for drug and vaccine development. Malaria parasites have a unique life cycle alternating between vector and host organism with a population bottleneck at each transition. These recurrent bottlenecks could influence the patterns of genetic diversity and the power of existing population genetic tools to identify sites under positive selection. We therefore simulated the site-frequency spectrum of a beneficial mutant allele through time under the malaria life cycle. We investigated the power of current population genetic methods to detect positive selection based on the site-frequency spectrum as well as temporal changes in allele frequency. We found that a within-host selective advantage is difficult to detect using these methods. Although a between-host transmission advantage could be detected, the power is decreased when compared with the classical Wright–Fisher (WF) population model. Using an adjusted null site-frequency spectrum that takes the malaria life cycle into account, the power of tests based on the site-frequency spectrum to detect positive selection is greatly improved. Our study demonstrates the importance of considering the life cycle in genetic analysis, especially in parasites with complex life cycles. |
format | Online Article Text |
id | pubmed-4139472 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Cambridge University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-41394722015-02-07 Recurrent bottlenecks in the malaria life cycle obscure signals of positive selection CHANG, HSIAO-HAN HARTL, DANIEL L. Parasitology Research Article Detecting signals of selection in the genome of malaria parasites is a key to identify targets for drug and vaccine development. Malaria parasites have a unique life cycle alternating between vector and host organism with a population bottleneck at each transition. These recurrent bottlenecks could influence the patterns of genetic diversity and the power of existing population genetic tools to identify sites under positive selection. We therefore simulated the site-frequency spectrum of a beneficial mutant allele through time under the malaria life cycle. We investigated the power of current population genetic methods to detect positive selection based on the site-frequency spectrum as well as temporal changes in allele frequency. We found that a within-host selective advantage is difficult to detect using these methods. Although a between-host transmission advantage could be detected, the power is decreased when compared with the classical Wright–Fisher (WF) population model. Using an adjusted null site-frequency spectrum that takes the malaria life cycle into account, the power of tests based on the site-frequency spectrum to detect positive selection is greatly improved. Our study demonstrates the importance of considering the life cycle in genetic analysis, especially in parasites with complex life cycles. Cambridge University Press 2015-02 2014-02-20 /pmc/articles/PMC4139472/ /pubmed/24560397 http://dx.doi.org/10.1017/S0031182014000067 Text en © Cambridge University Press 2014 The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence <http://creativecommons.org/licenses/by-nc-sa/3.0/>. The written permission of Cambridge University Press must be obtained for commercial re-use. |
spellingShingle | Research Article CHANG, HSIAO-HAN HARTL, DANIEL L. Recurrent bottlenecks in the malaria life cycle obscure signals of positive selection |
title | Recurrent bottlenecks in the malaria life cycle obscure signals of positive selection |
title_full | Recurrent bottlenecks in the malaria life cycle obscure signals of positive selection |
title_fullStr | Recurrent bottlenecks in the malaria life cycle obscure signals of positive selection |
title_full_unstemmed | Recurrent bottlenecks in the malaria life cycle obscure signals of positive selection |
title_short | Recurrent bottlenecks in the malaria life cycle obscure signals of positive selection |
title_sort | recurrent bottlenecks in the malaria life cycle obscure signals of positive selection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139472/ https://www.ncbi.nlm.nih.gov/pubmed/24560397 http://dx.doi.org/10.1017/S0031182014000067 |
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