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Genetic conflicts with Plasmodium parasites and functional constraints shape the evolution of erythrocyte cytoskeletal proteins

Plasmodium parasites exerted a strong selective pressure on primate genomes and mutations in genes encoding erythrocyte cytoskeleton proteins (ECP) determine protective effects against Plasmodium infection/pathogenesis. We thus hypothesized that ECP-encoding genes have evolved in response to Plasmod...

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Autores principales: Sironi, Manuela, Forni, Diego, Clerici, Mario, Cagliani, Rachele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168477/
https://www.ncbi.nlm.nih.gov/pubmed/30279439
http://dx.doi.org/10.1038/s41598-018-33049-y
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author Sironi, Manuela
Forni, Diego
Clerici, Mario
Cagliani, Rachele
author_facet Sironi, Manuela
Forni, Diego
Clerici, Mario
Cagliani, Rachele
author_sort Sironi, Manuela
collection PubMed
description Plasmodium parasites exerted a strong selective pressure on primate genomes and mutations in genes encoding erythrocyte cytoskeleton proteins (ECP) determine protective effects against Plasmodium infection/pathogenesis. We thus hypothesized that ECP-encoding genes have evolved in response to Plasmodium-driven selection. We analyzed the evolutionary history of 15 ECP-encoding genes in primates, as well as of their Plasmodium-encoded ligands (KAHRP, MESA and EMP3). Results indicated that EPB42, SLC4A1, and SPTA1 evolved under pervasive positive selection and that episodes of positive selection tended to occur more frequently in primate species that host a larger number of Plasmodium parasites. Conversely, several genes, including ANK1 and SPTB, displayed extensive signatures of purifying selection in primate phylogenies, Homininae lineages, and human populations, suggesting strong functional constraints. Analysis of Plasmodium genes indicated adaptive evolution in MESA and KAHRP; in the latter, different positively selected sites were located in the spectrin-binding domains. Because most of the positively selected sites in alpha-spectrin localized to the domains involved in the interaction with KAHRP, we suggest that the two proteins are engaged in an arms-race scenario. This observation is relevant because KAHRP is essential for the formation of “knobs”, which represent a major virulence determinant for P. falciparum.
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spelling pubmed-61684772018-10-05 Genetic conflicts with Plasmodium parasites and functional constraints shape the evolution of erythrocyte cytoskeletal proteins Sironi, Manuela Forni, Diego Clerici, Mario Cagliani, Rachele Sci Rep Article Plasmodium parasites exerted a strong selective pressure on primate genomes and mutations in genes encoding erythrocyte cytoskeleton proteins (ECP) determine protective effects against Plasmodium infection/pathogenesis. We thus hypothesized that ECP-encoding genes have evolved in response to Plasmodium-driven selection. We analyzed the evolutionary history of 15 ECP-encoding genes in primates, as well as of their Plasmodium-encoded ligands (KAHRP, MESA and EMP3). Results indicated that EPB42, SLC4A1, and SPTA1 evolved under pervasive positive selection and that episodes of positive selection tended to occur more frequently in primate species that host a larger number of Plasmodium parasites. Conversely, several genes, including ANK1 and SPTB, displayed extensive signatures of purifying selection in primate phylogenies, Homininae lineages, and human populations, suggesting strong functional constraints. Analysis of Plasmodium genes indicated adaptive evolution in MESA and KAHRP; in the latter, different positively selected sites were located in the spectrin-binding domains. Because most of the positively selected sites in alpha-spectrin localized to the domains involved in the interaction with KAHRP, we suggest that the two proteins are engaged in an arms-race scenario. This observation is relevant because KAHRP is essential for the formation of “knobs”, which represent a major virulence determinant for P. falciparum. Nature Publishing Group UK 2018-10-02 /pmc/articles/PMC6168477/ /pubmed/30279439 http://dx.doi.org/10.1038/s41598-018-33049-y Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Sironi, Manuela
Forni, Diego
Clerici, Mario
Cagliani, Rachele
Genetic conflicts with Plasmodium parasites and functional constraints shape the evolution of erythrocyte cytoskeletal proteins
title Genetic conflicts with Plasmodium parasites and functional constraints shape the evolution of erythrocyte cytoskeletal proteins
title_full Genetic conflicts with Plasmodium parasites and functional constraints shape the evolution of erythrocyte cytoskeletal proteins
title_fullStr Genetic conflicts with Plasmodium parasites and functional constraints shape the evolution of erythrocyte cytoskeletal proteins
title_full_unstemmed Genetic conflicts with Plasmodium parasites and functional constraints shape the evolution of erythrocyte cytoskeletal proteins
title_short Genetic conflicts with Plasmodium parasites and functional constraints shape the evolution of erythrocyte cytoskeletal proteins
title_sort genetic conflicts with plasmodium parasites and functional constraints shape the evolution of erythrocyte cytoskeletal proteins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168477/
https://www.ncbi.nlm.nih.gov/pubmed/30279439
http://dx.doi.org/10.1038/s41598-018-33049-y
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