Population genetics of Plasmodium resistance genes in Anopheles gambiae: no evidence for strong selection

Anopheles mosquitoes are the primary vectors for malaria in Africa, transmitting the disease to more than 100 million people annually. Recent functional studies have revealed mosquito genes that are crucial for Plasmodium development, but there is presently little understanding of which genes mediate vector competence in the wild, or evolve in response to parasite‐mediated selection. Here, we use population genetic approaches to study the strength and mode of natural selection on a suite of mosquito immune system genes, CTL4, CTLMA2, LRIM1, and APL2 (LRRD7), which have been shown to affect Plasmodium development in functional studies. We sampled these genes from two African populations of An. gambiae s.s., along with several closely related species, and conclude that there is no evidence for either strong directional or balancing selection on these genes. We highlight a number of challenges that need to be met in order to apply population genetic tests for selection in Anopheles mosquitoes; in particular the dearth of suitable outgroup species and the potential difficulties that arise when working within a closely‐related species complex.

[1]  J. Kayondo,et al.  Molecular karyotyping of the 2La inversion in Anopheles gambiae. , 2007, The American journal of tropical medicine and hygiene.

[2]  M. Donnelly,et al.  Ecological Zones Rather Than Molecular Forms Predict Genetic Differentiation in the Malaria Vector Anopheles gambiae s.s. in Ghana , 2007, Genetics.

[3]  G. Christophides,et al.  Anopheles and Plasmodium: from laboratory models to natural systems in the field , 2006, EMBO reports.

[4]  F. Tripet,et al.  Evidence for subdivision within the M molecular form of Anopheles gambiae , 2006, Molecular ecology.

[5]  M. Coetzee,et al.  Dieldrin resistance in the malaria vector Anopheles gambiae in Ghana , 2006, Medical and veterinary entomology.

[6]  H. Taylor,et al.  AgDscam, a Hypervariable Immunoglobulin Domain-Containing Receptor of the Anopheles gambiae Innate Immune System , 2006, PLoS biology.

[7]  Emmanuel Mongin,et al.  Anopheles gambiae Immune Responses to Human and Rodent Plasmodium Parasite Species , 2006, PLoS pathogens.

[8]  Mark Kirkpatrick,et al.  Chromosome Inversions, Local Adaptation and Speciation , 2006, Genetics.

[9]  L. Kruglyak,et al.  Natural Malaria Infection in Anopheles gambiae Is Regulated by a Single Genomic Control Region , 2006, Science.

[10]  Frédéric Simard,et al.  Breakpoint structure reveals the unique origin of an interspecific chromosomal inversion (2La) in the Anopheles gambiae complex. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[11]  D. Charlesworth.  Balancing Selection and Its Effects on Sequences in Nearby Genome Regions , 2006, PLoS genetics.

[12]  D. Halligan,et al.  Natural Selection Drives Extremely Rapid Evolution in Antiviral RNAi Genes , 2006, Current Biology.

[13]  W. Anderson,et al.  Mechanisms of Genetic Exchange Within the Chromosomal Inversions of Drosophila pseudoobscura , 2005, Genetics.

[14]  T. Little,et al.  The evolution of immune‐related genes from disease carrying mosquitoes: diversity in a peptidoglycan‐ and a thioester‐recognizing protein , 2005, Insect molecular biology.

[15]  J. Slate.  Molecular evolution of the sheep prion protein gene , 2005, Proceedings of the Royal Society B: Biological Sciences.

[16]  R. Nielsen.  Molecular signatures of natural selection. , 2005, Annual review of genetics.

[17]  S. Higgs,et al.  An immune-responsive serpin, SRPN6, mediates mosquito defense against malaria parasites. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[18]  T. Gibson,et al.  Anopheles gambiae SRPN2 facilitates midgut invasion by the malaria parasite Plasmodium berghei , 2005, EMBO reports.

[19]  Matthew W. Hahn,et al.  Genomic Islands of Speciation in Anopheles gambiae , 2005, PLoS biology.

[20]  F. Kafatos,et al.  The complex interplay between mosquito positive and negative regulators of Plasmodium development. , 2005, Current opinion in microbiology.

[21]  R. Butlin.  Recombination and speciation , 2005, Molecular ecology.

[22]  M. Beaumont.  Adaptation and speciation: what can F(st) tell us? , 2005, Trends in ecology & evolution.

[23]  J. Powell,et al.  Differential introgression of chromsomal regions between Anopheles gambiae and An. arabiensis. , 2005, The American journal of tropical medicine and hygiene.

[24]  F. Kafatos,et al.  Mosquito immunity against Plasmodium. , 2005, Insect biochemistry and molecular biology.

[25]  F. Ayala,et al.  Chromosome speciation: Humans, Drosophila, and mosquitoes , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[26]  R. Harbach.  The classification of genus Anopheles (Diptera: Culicidae): a working hypothesis of phylogenetic relationships. , 2004, Bulletin of entomological research.

[27]  Florian Meereis,et al.  PCOGR: Phylogenetic COG ranking as an online tool to judge the specificity of COGs with respect to freely definable groups of organisms , 2004, BMC Bioinformatics.

[28]  Sudhir Kumar,et al.  MEGA3: Integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment , 2004, Briefings Bioinform..

[29]  G. Christophides,et al.  Effects of Mosquito Genes on Plasmodium Development , 2004, Science.

[30]  C. Janse,et al.  Complement-Like Protein TEP1 Is a Determinant of Vectorial Capacity in the Malaria Vector Anopheles gambiae , 2004, Cell.

[31]  J. Pinto,et al.  Revisiting the role of introgression vs shared ancestral polymorphisms as key processes shaping genetic diversity in the recently separated sibling species of the Anopheles gambiae complex , 2004, Heredity.

[32]  Xavier Messeguer,et al.  DnaSP, DNA polymorphism analyses by the coalescent and other methods , 2003, Bioinform..

[33]  M. Ferdig,et al.  DNA barcoding of parasites and invertebrate disease vectors: what you don't know can hurt you. , 2003, Trends in parasitology.

[34]  J. Krzywinski,et al.  Semipermeable species boundaries between Anopheles gambiae and Anopheles arabiensis: Evidence from multilocus DNA sequence variation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[35]  D. Begun,et al.  Natural selection drives Drosophila immune system evolution. , 2003, Genetics.

[36]  J. Powell,et al.  Speciation Within Anopheles gambiae-- the Glass Is Half Full , 2002, Science.

[37]  Jian Wang,et al.  The Genome Sequence of the Malaria Mosquito Anopheles gambiae , 2002, Science.

[38]  E. Birney,et al.  Immunity-Related Genes and Gene Families in Anopheles gambiae , 2002, Science.

[39]  A. della Torre,et al.  A Polytene Chromosome Analysis of the Anopheles gambiae Species Complex , 2002, Science.

[40]  P. Andolfatto,et al.  Inversion polymorphisms and nucleotide variability in Drosophila. , 2001, Genetical research.

[41]  Ziheng Yang,et al.  Statistical methods for detecting molecular adaptation , 2000, Trends in Ecology & Evolution.

[42]  W. Stephan,et al.  Joint effects of genetic hitchhiking and background selection on neutral variation. , 2000, Genetics.

[43]  Justin C. Fay,et al.  Hitchhiking under positive Darwinian selection. , 2000, Genetics.

[44]  R. Hunt,et al.  Resistance to dieldrin + fipronil assorts with chromosome inversion 2La in the malaria vector Anopheles gambiae , 2000, Medical and veterinary entomology.

[45]  E. Stahl,et al.  Dynamics of disease resistance polymorphism at the Rpm1 locus of Arabidopsis , 1999, Nature.

[46]  Laurence D. Hurst,et al.  Do essential genes evolve slowly? , 1999, Current Biology.

[47]  I. Kitching,et al.  Phylogeny of the Pyretophorus Series of Anopheles subgenus Cellia (Diptera: Culicidae) , 1999 .

[48]  D. Yeates,et al.  Evolution and systematics of Anopheles: insights from a molecular phylogeny of Australasian mosquitoes. , 1998, Molecular phylogenetics and evolution.

[49]  R. Hunt,et al.  The Anopheles gambiae complex: a new species from Ethiopia. , 1998, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[50]  A. Lanfrancotti,et al.  Molecular identification of sympatric chromosomal forms of Anopheles gambiae and further evidence of their reproductive isolation , 1997, Insect molecular biology.

[51]  Ziheng Yang,et al.  PAML: a program package for phylogenetic analysis by maximum likelihood , 1997, Comput. Appl. Biosci..

[52]  H. Erfle,et al.  Quantitative trait loci for refractoriness of Anopheles gambiae to Plasmodium cynomolgi B. , 1997, Science.

[53]  L. Kann,et al.  Excess amino acid polymorphism in mitochondrial DNA: contrasts among genes from Drosophila, mice, and humans. , 1996, Molecular biology and evolution.

[54]  W Stephan,et al.  The hitchhiking effect on the site frequency spectrum of DNA polymorphisms. , 1995, Genetics.

[55]  D. M. Hamm,et al.  Molecular phylogeny of the Anopheles gambiae complex suggests genetic introgression between principal malaria vectors. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[56]  F. Collins,et al.  Identification of single specimens of the Anopheles gambiae complex by the polymerase chain reaction. , 1993, The American journal of tropical medicine and hygiene.

[57]  W. Li,et al.  Statistical tests of neutrality of mutations. , 1993, Genetics.

[58]  M. Coluzzi.  Malaria vector analysis and control. , 1992, Parasitology today.

[59]  J. Beier,et al.  Intraspecific chromosomal polymorphism in the Anopheles gambiae complex as a factor affecting malaria transmission in the Kisumu area of Kenya. , 1992, The American journal of tropical medicine and hygiene.

[60]  M. Kreitman,et al.  Adaptive protein evolution at the Adh locus in Drosophila , 1991, Nature.

[61]  N L Kaplan,et al.  The "hitchhiking effect" revisited. , 1989, Genetics.

[62]  F. Tajima.  The effect of change in population size on DNA polymorphism. , 1989, Genetics.

[63]  F. Tajima.  Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. , 1989, Genetics.

[64]  K. Vernick,et al.  Association of a Plasmodium-refractory phenotype with an esterase locus in Anopheles gambiae. , 1989, The American journal of tropical medicine and hygiene.

[65]  J. Seger.  Dynamics of some simple host-parasite models with more than two genotypes in each species. , 1988, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[66]  R. Hudson,et al.  A test of neutral molecular evolution based on nucleotide data. , 1987, Genetics.

[67]  M. Nei.  Molecular Evolutionary Genetics , 1987 .

[68]  G. A. Watterson.  On the number of segregating sites in genetical models without recombination. , 1975, Theoretical population biology.

[69]  G. White.  Chromosomal Evidence for Natural Interspecific Hybridization by Mosquitoes of the Anopheles gambiae Complex , 1971, Nature.

[70]  Weltgesundheitsorganisation.  World malaria report , 2005 .

[71]  G. White.  Anopheles gambiae complex and disease transmission in Africa. , 1974, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[72]  J. M. Smith,et al.  The hitch-hiking effect of a favourable gene. , 1974, Genetical research.