Limits...
Exceptional diversity, maintenance of polymorphism, and recent directional selection on the APL1 malaria resistance genes of Anopheles gambiae.

Rottschaefer SM, Riehle MM, Coulibaly B, Sacko M, Niaré O, Morlais I, Traoré SF, Vernick KD, Lazzaro BP - PLoS Biol. (2011)

Bottom Line: Variation at APL1 is highly structured across geographic and temporal subpopulations.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Entomology, Cornell University, Ithaca, New York, United States of America.

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.

Show MeSH

Related in: MedlinePlus

Number of observations of mosquitoes with each 2La inversion karyotype in each molecular form (M and S) over each sample collection.Population frequencies (in percentages) are given in the margins of each table. “Unk.” indicates that 2La karyotype was not determined.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3050937&req=5

pbio-1000600-g003: Number of observations of mosquitoes with each 2La inversion karyotype in each molecular form (M and S) over each sample collection.Population frequencies (in percentages) are given in the margins of each table. “Unk.” indicates that 2La karyotype was not determined.

Mentions: The APL1 locus lies approximately 1 Mbp inside the distal breakpoint of the polymorphic chromosomal inversion 2La, which has previously been shown to exhibit geographic and microecological variation in frequency. The “inverted” form (2Laa) of the inversion is more common in drier, more arid environments, and the “standard” orientation (2La+) predominates in moister locales [35],[36]. We therefore hypothesized that alternate APL1 alleles could be associated with the distinct 2La arrangements and that differences in the frequency of the alternate 2La arrangements might underlie the genetic differentiation we observe at APL1 across our collections. The 2Laa orientation is nearly fixed in the Bancoumana collections, but both arrangements are segregating in the Toumani-Oulena and Makouchetoum collections (Figure 3). To test the hypothesis that divergence between 2Laa and 2La+ chromosomes is responsible for our observed substructure at APL1, we measured differentiation in all three APL1 paralogs after grouping alleles by 2La karyotype irrespective of collection origin. Since it is not possible to identify which of the two homologous chromosomes any APL1 sequence is derived from in a diploid individual, this analysis can only be conducted using homokaryotypic individuals. The 2La inversion does not segregate in the individuals that were recovered from the Bancoumana dry season collection (all mosquitoes have 2Laa/2Laa homokaryotypes), so we conservatively restricted our analysis of population structure across the inversion to S form mosquitoes from the three rainy season collections. There was mild differentiation between 2Laa/2Laa and 2La+/2La+ mosquitoes at all three APL1 paralogs within the S form (APL1A: Kst* = 0.059, p = 0.016; APL1B: Kst* = 0.014, p = 0.094; APL1C: Kst* = 0.050, p = 0.004). Inclusion of all mosquitoes, including the 2Laa/2Laa dry season mosquitoes from Bancoumana in this analysis, results in stronger differentiation at all three APL1 paralogs, although the inclusion of these mosquitoes conflates the effects of 2La and the “M” and “S” molecular forms (discussed below). No major differences in the amount of APL1 genetic diversity were observed between 2La+/2La+ and 2Laa/2Laa homokaryotypes. The differentiation we attribute to 2La is significant and potentially underestimated because our analysis is necessarily restricted to the comparatively small number of homokaryotypic individuals, but it seems to be less severe than the differentiation observed when mosquitoes are categorized by M/S molecular form.


Exceptional diversity, maintenance of polymorphism, and recent directional selection on the APL1 malaria resistance genes of Anopheles gambiae.

Rottschaefer SM, Riehle MM, Coulibaly B, Sacko M, Niaré O, Morlais I, Traoré SF, Vernick KD, Lazzaro BP - PLoS Biol. (2011)

Number of observations of mosquitoes with each 2La inversion karyotype in each molecular form (M and S) over each sample collection.Population frequencies (in percentages) are given in the margins of each table. “Unk.” indicates that 2La karyotype was not determined.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3050937&req=5

pbio-1000600-g003: Number of observations of mosquitoes with each 2La inversion karyotype in each molecular form (M and S) over each sample collection.Population frequencies (in percentages) are given in the margins of each table. “Unk.” indicates that 2La karyotype was not determined.
Mentions: The APL1 locus lies approximately 1 Mbp inside the distal breakpoint of the polymorphic chromosomal inversion 2La, which has previously been shown to exhibit geographic and microecological variation in frequency. The “inverted” form (2Laa) of the inversion is more common in drier, more arid environments, and the “standard” orientation (2La+) predominates in moister locales [35],[36]. We therefore hypothesized that alternate APL1 alleles could be associated with the distinct 2La arrangements and that differences in the frequency of the alternate 2La arrangements might underlie the genetic differentiation we observe at APL1 across our collections. The 2Laa orientation is nearly fixed in the Bancoumana collections, but both arrangements are segregating in the Toumani-Oulena and Makouchetoum collections (Figure 3). To test the hypothesis that divergence between 2Laa and 2La+ chromosomes is responsible for our observed substructure at APL1, we measured differentiation in all three APL1 paralogs after grouping alleles by 2La karyotype irrespective of collection origin. Since it is not possible to identify which of the two homologous chromosomes any APL1 sequence is derived from in a diploid individual, this analysis can only be conducted using homokaryotypic individuals. The 2La inversion does not segregate in the individuals that were recovered from the Bancoumana dry season collection (all mosquitoes have 2Laa/2Laa homokaryotypes), so we conservatively restricted our analysis of population structure across the inversion to S form mosquitoes from the three rainy season collections. There was mild differentiation between 2Laa/2Laa and 2La+/2La+ mosquitoes at all three APL1 paralogs within the S form (APL1A: Kst* = 0.059, p = 0.016; APL1B: Kst* = 0.014, p = 0.094; APL1C: Kst* = 0.050, p = 0.004). Inclusion of all mosquitoes, including the 2Laa/2Laa dry season mosquitoes from Bancoumana in this analysis, results in stronger differentiation at all three APL1 paralogs, although the inclusion of these mosquitoes conflates the effects of 2La and the “M” and “S” molecular forms (discussed below). No major differences in the amount of APL1 genetic diversity were observed between 2La+/2La+ and 2Laa/2Laa homokaryotypes. The differentiation we attribute to 2La is significant and potentially underestimated because our analysis is necessarily restricted to the comparatively small number of homokaryotypic individuals, but it seems to be less severe than the differentiation observed when mosquitoes are categorized by M/S molecular form.

Bottom Line: Variation at APL1 is highly structured across geographic and temporal subpopulations.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Entomology, Cornell University, Ithaca, New York, United States of America.

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.

Show MeSH
Related in: MedlinePlus