Footprints of positive selection associated with a mutation (N1575Y) in the voltage-gated sodium channel of Anopheles gambiae

Jones, Christopher ORCID: https://orcid.org/0000-0002-6504-6224, Liyanapathirana, Milindu, Agossa, Fiacre R., Weetman, David ORCID: https://orcid.org/0000-0002-5820-1388, Ranson, Hilary ORCID: https://orcid.org/0000-0003-2332-8247, Donnelly, Martin James ORCID: https://orcid.org/0000-0001-5218-1497 and Wilding, Craig (2012) 'Footprints of positive selection associated with a mutation (N1575Y) in the voltage-gated sodium channel of Anopheles gambiae'. Proceedings of the National Academy of Sciences, Vol 109, Issue 17, pp. 6614-6619.

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Abstract

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 extending
over 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 extended
LD 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).

Item Type:	Article
Uncontrolled Keywords:	kdr; selective sweep; inactivation particle
Subjects:	QU Biochemistry > Genetics > QU 500 Genetic phenomena QX Parasitology > Insects. Other Parasites > QX 515 Anopheles QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control
Digital Object Identifer (DOI):	https://doi.org/10.1073/pnas.1201475109
Depositing User:	Users 183 not found.
Date Deposited:	11 Apr 2012 14:03
Last Modified:	07 Jun 2022 11:09
URI:	https://archive.lstmed.ac.uk/id/eprint/2828

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