Immune defense genes are sometimes highly variable in host populations, reflecting selective pressure to combat diverse pathogens. In other instances, where there are only a few dominant pathogens, natural selection may favor only one or a few defense alleles. Here, we show that both adaptive strategies can occur in the same genes under different circumstances.
We examined diversity in the APL1 genes of the human malaria vector mosquito Anophleles gambiae, which play a role in defense against malaria parasites. We found that the APL1 genes are exceptionally polymorphic, being 10-fold more diverse than typical A. gambiae genes.
Full Title: “Exceptional Diversity, Maintenance of Polymorphism, and Recent Directional Selection on the APL1 Malaria Resistance Genes of Anopheles gambiae.”
The distribution of APL1 allelic diversity, however, is strongly structured depending on whether the genes are carried by the M or S “molecular forms” of the vector, which are thought to constitute newly forming species. We show that despite the evolutionary maintenance of APL1 diversity in the S form of A. gambiae, there is evidence of strong recent directional selection on APL1 genes in the M form. Independent research has shown that Tep1, a gene which encodes a protein that physically interacts with the APL1C protein, also harbors high allelic diversity in the S form and shows evidence of recent directional selection in the M form, suggesting that the evolutionary trajectories of the Tep1 and APL1 defense loci may be correlated.
Susan M. Rottschaefer1, Michelle M. Riehle2, Boubacar Coulibaly3, Madjou Sacko3, Oumou Niaré3, Isabelle Morlais4, Sekou F. Traoré3, Kenneth D. Vernick5, Brian P. Lazzaro1*
1 Department of Entomology, Cornell University, Ithaca, New York, United States of America, 2 Department of Microbiology, University of Minnesota, Saint Paul, Minnesota, United States of America, 3 Malaria Research and Training Center, University of Bamako, Bamako, Mali, 4 Laboratoire de Recherche sur le Paludisme, Institut de Recherche pour le Développement IRD-OCEAC, Yaoundé, Cameroun, 5 Unit of Insect Vector Genetics and Genomics, Institut Pasteur, Paris, France
Abstract: The three-gene APL1 locus encodes essential components of the mosquito immune defense against malaria parasites. APL1 was originally identified because it lies within a mapped QTL conferring the vector mosquito Anopheles gambiae natural resistance to the human malaria parasite, Plasmodium falciparum, and APL1 genes have subsequently been shown to be involved in defense against several species of Plasmodium. Here, we examine molecular population genetic variation at the APL1 gene cluster in spatially and temporally diverse West African collections of A. gambiae. The locus is extremely polymorphic, showing evidence of adaptive evolutionary maintenance of genetic variation. We hypothesize that this variability aids in defense against genetically diverse pathogens, including Plasmodium. Variation at APL1 is highly structured across geographic and temporal subpopulations. In particular, diversity is exceptionally high during the rainy season, when malaria transmission rates are at their peak. Much less allelic diversity is observed during the dry season when mosquito population sizes and malaria transmission rates are low. APL1 diversity is weakly stratified by the polymorphic 2La chromosomal inversion but is very strongly subdivided between the M and S “molecular forms.” We find evidence that a recent selective sweep has occurred at the APL1 locus in M form mosquitoes only. The independently reported observation of a similar M-form restricted sweep at the Tep1 locus, whose product physically interacts with APL1C, suggests that epistatic selection may act on these two loci causing them to sweep coordinately.
Author Summary: Immune defense genes are sometimes highly variable in host populations, reflecting selective pressure to combat diverse pathogens. In other instances, where there are only a few dominant pathogens, natural selection may favor only one or a few defense alleles. Here, we show that both adaptive strategies can occur in the same genes under different circumstances. We examined diversity in the APL1 genes of the human malaria vector mosquito Anophleles gambiae, which play a role in defense against malaria parasites. We found that the APL1 genes are exceptionally polymorphic, being 10-fold more diverse than typical A. gambiae genes. The distribution of APL1 allelic diversity, however, is strongly structured depending on whether the genes are carried by the M or S “molecular forms” of the vector, which are thought to constitute newly forming species. We show that despite the evolutionary maintenance of APL1 diversity in the S form of A. gambiae, there is evidence of strong recent directional selection on APL1 genes in the M form. Independent research has shown that Tep1, a gene which encodes a protein that physically interacts with the APL1C protein, also harbors high allelic diversity in the S form and shows evidence of recent directional selection in the M form, suggesting that the evolutionary trajectories of the Tep1 and APL1 defense loci may be correlated.
Citation: Rottschaefer SM, Riehle MM, Coulibaly B, Sacko M, Niaré O, et al. (2011) Exceptional Diversity, Maintenance of Polymorphism, and Recent Directional Selection on the APL1 Malaria Resistance Genes of Anopheles gambiae. PLoS Biol 9(3): e1000600. doi:10.1371/journal.pbio.1000600
Academic Editor: David S. Schneider, Stanford University, United States of America
Full Text: Exceptional Diversity, Maintenance of Polymorphism, and Recent Directional Selection on the APL1 Malaria Resistance Genes of Anopheles gambiae (PDF)
Copyright: © 2011 Rottschaefer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by National Institutes of Health grant R01 AI062995. The funding agency had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: LRR, leucine-rich repeat; QTL, quantitative trait locus