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标题：Declines in prevalence alter the optimal level of sexual investment for the malaria parasite Plasmodium falciparum
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作者：Angela M. Early ; Flavia Camponovo ; Stéphane Pelleau 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：30
DOI：10.1073/pnas.2122165119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance Like most human pathogens, the malaria parasite Plasmodium falciparum experiences strong selection pressure from public health interventions such as drug treatment. While most commonly studied in the context of drug targets and related pathways, parasite adaptation to control measures likely extends to phenotypes beyond drug resistance. Here, we use modeling to explore how control measures can reduce levels of within-host competition between P. falciparum genotypes and favor higher rates of sexual investment. We validate these predictions with longitudinally sampled genomic data from French Guiana during a period of malaria decline and find that the most strongly selected genes are enriched for transcription factors involved in commitment to and development of the parasite’s sexual gametocyte form. Successful infectious disease interventions can result in large reductions in parasite prevalence. Such demographic change has fitness implications for individual parasites and may shift the parasite’s optimal life history strategy. Here, we explore whether declining infection rates can alter Plasmodium falciparum’s investment in sexual versus asexual growth. Using a multiscale mathematical model, we demonstrate how the proportion of polyclonal infections, which decreases as parasite prevalence declines, affects the optimal sexual development strategy: Within-host competition in multiclone infections favors a greater investment in asexual growth whereas single-clone infections benefit from higher conversion to sexual forms. At the same time, drug treatment also imposes selection pressure on sexual development by shortening infection length and reducing within-host competition. We assess these models using 148 P. falciparum parasite genomes sampled in French Guiana over an 18-y period of intensive intervention (1998 to 2015). During this time frame, multiple public health measures, including the introduction of new drugs and expanded rapid diagnostic testing, were implemented, reducing P. falciparum malaria cases by an order of magnitude. Consistent with this prevalence decline, we see an increase in the relatedness among parasites, but no single clonal background grew to dominate the population. Analyzing individual allele frequency trajectories, we identify genes that likely experienced selective sweeps. Supporting our model predictions, genes showing the strongest signatures of selection include transcription factors involved in the development of P. falciparum’s sexual gametocyte form. These results highlight how public health interventions impose wide-ranging selection pressures that affect basic parasite life history traits.
关键词：enmalariasexual commitmentadaptationmodelinggenomics