Evolution of Host Specificity by Malaria Parasites through Altered Mechanisms Controlling Genome Maintenance

ABSTRACT The protozoan parasites that cause malaria infect a wide variety of vertebrate hosts, including birds, reptiles, and mammals, and the evolutionary pressures inherent to the host-parasite relationship have profoundly shaped the genomes of both host and parasite. Here, we report that these se...

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Autores principales:	Michelle C. Siao, Janus Borner, Susan L. Perkins, Kirk W. Deitsch, Laura A. Kirkman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	DNA repair antigenic variation evolution malaria Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1b641e93a574455385147c953cc5bf20
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spelling	oai:doaj.org-article:1b641e93a574455385147c953cc5bf202021-11-15T15:57:03ZEvolution of Host Specificity by Malaria Parasites through Altered Mechanisms Controlling Genome Maintenance10.1128/mBio.03272-192150-7511https://doaj.org/article/1b641e93a574455385147c953cc5bf202020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.03272-19https://doaj.org/toc/2150-7511ABSTRACT The protozoan parasites that cause malaria infect a wide variety of vertebrate hosts, including birds, reptiles, and mammals, and the evolutionary pressures inherent to the host-parasite relationship have profoundly shaped the genomes of both host and parasite. Here, we report that these selective pressures have resulted in unexpected alterations to one of the most basic aspects of eukaryotic biology, the maintenance of genome integrity through DNA repair. Malaria parasites that infect humans continuously generate genetic diversity within their antigen-encoding gene families through frequent ectopic recombination between gene family members, a process that is a crucial feature of the persistence of malaria globally. The continuous generation of antigen diversity ensures that different parasite isolates are antigenically distinct, thus preventing extensive cross-reactive immunity and enabling parasites to maintain stable transmission within human populations. However, the molecular basis of the recombination between gene family members is not well understood. Through computational analyses of the antigen-encoding, multicopy gene families of different Plasmodium species, we report the unexpected observation that malaria parasites that infect rodents do not display the same degree of antigen diversity as observed in Plasmodium falciparum and appear to undergo significantly less ectopic recombination. Using comparative genomics, we also identify key molecular components of the diversification process, thus shedding new light on how malaria parasites balance the maintenance of genome integrity with the requirement for continuous genetic diversification. IMPORTANCE Malaria remains one of the most prevalent and deadly infectious diseases of the developing world, causing approximately 228 million clinical cases and nearly half a million deaths annually. The disease is caused by protozoan parasites of the genus Plasmodium, and of the five species capable of infecting humans, infections with P. falciparum are the most severe. In addition to the parasites that infect people, there are hundreds of additional species that infect birds, reptiles, and other mammals, each exquisitely evolved to meet the specific challenges inherent to survival within their respective hosts. By comparing the unique strategies that each species has evolved, key insights into host-parasite interactions can be gained, including discoveries regarding the pathogenesis of human disease. Here, we describe the surprising observation that closely related parasites with different hosts have evolved remarkably different methods for repairing their genomes. This observation has important implications for the ability of parasites to maintain chronic infections and for the development of host immunity.Michelle C. SiaoJanus BornerSusan L. PerkinsKirk W. DeitschLaura A. KirkmanAmerican Society for MicrobiologyarticleDNA repairantigenic variationevolutionmalariaMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	DNA repair antigenic variation evolution malaria Microbiology QR1-502
spellingShingle	DNA repair antigenic variation evolution malaria Microbiology QR1-502 Michelle C. Siao Janus Borner Susan L. Perkins Kirk W. Deitsch Laura A. Kirkman Evolution of Host Specificity by Malaria Parasites through Altered Mechanisms Controlling Genome Maintenance
description	ABSTRACT The protozoan parasites that cause malaria infect a wide variety of vertebrate hosts, including birds, reptiles, and mammals, and the evolutionary pressures inherent to the host-parasite relationship have profoundly shaped the genomes of both host and parasite. Here, we report that these selective pressures have resulted in unexpected alterations to one of the most basic aspects of eukaryotic biology, the maintenance of genome integrity through DNA repair. Malaria parasites that infect humans continuously generate genetic diversity within their antigen-encoding gene families through frequent ectopic recombination between gene family members, a process that is a crucial feature of the persistence of malaria globally. The continuous generation of antigen diversity ensures that different parasite isolates are antigenically distinct, thus preventing extensive cross-reactive immunity and enabling parasites to maintain stable transmission within human populations. However, the molecular basis of the recombination between gene family members is not well understood. Through computational analyses of the antigen-encoding, multicopy gene families of different Plasmodium species, we report the unexpected observation that malaria parasites that infect rodents do not display the same degree of antigen diversity as observed in Plasmodium falciparum and appear to undergo significantly less ectopic recombination. Using comparative genomics, we also identify key molecular components of the diversification process, thus shedding new light on how malaria parasites balance the maintenance of genome integrity with the requirement for continuous genetic diversification. IMPORTANCE Malaria remains one of the most prevalent and deadly infectious diseases of the developing world, causing approximately 228 million clinical cases and nearly half a million deaths annually. The disease is caused by protozoan parasites of the genus Plasmodium, and of the five species capable of infecting humans, infections with P. falciparum are the most severe. In addition to the parasites that infect people, there are hundreds of additional species that infect birds, reptiles, and other mammals, each exquisitely evolved to meet the specific challenges inherent to survival within their respective hosts. By comparing the unique strategies that each species has evolved, key insights into host-parasite interactions can be gained, including discoveries regarding the pathogenesis of human disease. Here, we describe the surprising observation that closely related parasites with different hosts have evolved remarkably different methods for repairing their genomes. This observation has important implications for the ability of parasites to maintain chronic infections and for the development of host immunity.
format	article
author	Michelle C. Siao Janus Borner Susan L. Perkins Kirk W. Deitsch Laura A. Kirkman
author_facet	Michelle C. Siao Janus Borner Susan L. Perkins Kirk W. Deitsch Laura A. Kirkman
author_sort	Michelle C. Siao
title	Evolution of Host Specificity by Malaria Parasites through Altered Mechanisms Controlling Genome Maintenance
title_short	Evolution of Host Specificity by Malaria Parasites through Altered Mechanisms Controlling Genome Maintenance
title_full	Evolution of Host Specificity by Malaria Parasites through Altered Mechanisms Controlling Genome Maintenance
title_fullStr	Evolution of Host Specificity by Malaria Parasites through Altered Mechanisms Controlling Genome Maintenance
title_full_unstemmed	Evolution of Host Specificity by Malaria Parasites through Altered Mechanisms Controlling Genome Maintenance
title_sort	evolution of host specificity by malaria parasites through altered mechanisms controlling genome maintenance
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/1b641e93a574455385147c953cc5bf20
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Evolution of Host Specificity by Malaria Parasites through Altered Mechanisms Controlling Genome Maintenance

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