TY - JOUR
T1 - Footprints of positive selection associated with a mutation (N1575Y) in the voltage-gated sodium channel of Anopheles gambiae
AU - Jones, Chris
AU - Liyanapathirana, Milindu
AU - Agossa, Fiacre R.
AU - Weetman, David
AU - Ranson, Hilary
AU - Donnelly, Martin
AU - Wilding, Craig S.
PY - 2012/4/24
Y1 - 2012/4/24
N2 - Insecticide resistance is an ideal model to study the emergence and spread of adaptative variants. In the African malaria mosquito, Anopheles gambiae, this is complemented by a strong public health rationale. In this insect, resistance to pyrethroid and DDT insecticides is strongly associated with the mutations L1014F and L1014S within the para voltage-gated sodium channel (VGSC). Across much of West Africa, 1014F frequency approaches fixation. Here, we document the emergence of a mutation, N1575Y, within the linker between domains III-IV of the VGSC. In data extendingover 40 kbp of the VGSC 1575Y occurs on only a single long-range haplotype, also bearing 1014F. The 1014F-1575Y haplotype was found in both M and S molecular forms of An. gambiae in West/Central African sample sites separated by up to 2,000 km. In Burkina Faso M form, 1575Y allele frequency rose significantly from 0.053 to 0.172 between 2008 and 2010. Extended haplotype homozygosity analysis of the wild-type 1575N allele showed rapid decay of linkage disequilibrium (LD), in sharp contrast to the extendedLD exhibited by 1575Y. A haplotype with long-range LD and high/increasing frequency is a classical sign of strong positive selection acting on a recent mutant. 1575Y occurs ubiquitously on a 1014F haplotypic background, suggesting that the N1575Y mutation compensates for deleterious fitness effects of 1014F and/or confers additional resistance to insecticides. Haplotypic tests of association suggest the latter: The 1014F-1575Y haplotype confers a significant additive benefit above 1014F-1575N for survival to DDT (M form P = 0.03) and permethrin (S form P = 0.003).
AB - Insecticide resistance is an ideal model to study the emergence and spread of adaptative variants. In the African malaria mosquito, Anopheles gambiae, this is complemented by a strong public health rationale. In this insect, resistance to pyrethroid and DDT insecticides is strongly associated with the mutations L1014F and L1014S within the para voltage-gated sodium channel (VGSC). Across much of West Africa, 1014F frequency approaches fixation. Here, we document the emergence of a mutation, N1575Y, within the linker between domains III-IV of the VGSC. In data extendingover 40 kbp of the VGSC 1575Y occurs on only a single long-range haplotype, also bearing 1014F. The 1014F-1575Y haplotype was found in both M and S molecular forms of An. gambiae in West/Central African sample sites separated by up to 2,000 km. In Burkina Faso M form, 1575Y allele frequency rose significantly from 0.053 to 0.172 between 2008 and 2010. Extended haplotype homozygosity analysis of the wild-type 1575N allele showed rapid decay of linkage disequilibrium (LD), in sharp contrast to the extendedLD exhibited by 1575Y. A haplotype with long-range LD and high/increasing frequency is a classical sign of strong positive selection acting on a recent mutant. 1575Y occurs ubiquitously on a 1014F haplotypic background, suggesting that the N1575Y mutation compensates for deleterious fitness effects of 1014F and/or confers additional resistance to insecticides. Haplotypic tests of association suggest the latter: The 1014F-1575Y haplotype confers a significant additive benefit above 1014F-1575N for survival to DDT (M form P = 0.03) and permethrin (S form P = 0.003).
KW - Inactivation particle
KW - Kdr
KW - Selective sweep
U2 - 10.1073/pnas.1201475109
DO - 10.1073/pnas.1201475109
M3 - Article
SN - 0027-8424
VL - 109
SP - 6614
EP - 6619
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 17
ER -
