No evidence for positive selection at two potential targets for malaria transmission-blocking vaccines in Anopheles gambiae s.s.
Human malaria causes nearly a million deaths in sub-Saharan Africa each year. The evolution of drug-resistance in the parasite and insecticide resistance in the mosquito vector has complicated control measures and made the need for new control strategies more urgent. Anopheles gambiae s.s. is one of the primary vectors of human malaria in Africa, and parasite-transmission-blocking vaccines targeting Anopheles proteins have been proposed as a possible strategy to control the spread of the disease. However, the success of these hypothetical technologies would depend on the successful ability to broadly target mosquito populations that may be genetically heterogeneous. Understanding the evolutionary pressures shaping genetic variation among candidate target molecules offers a first step towards evaluating the prospects of successfully deploying such technologies. We studied the population genetics of genes encoding two candidate target proteins, the salivary gland protein saglin and the basal lamina structural protein laminin, in wild populations of the M and S molecular forms of A. gambiae in Mali. Through analysis of intraspecific genetic variation and interspecific comparisons, we found no evidence of positive natural selection at the genes encoding these proteins. On the contrary, we found evidence for particularly strong purifying selection at the laminin gene. These results provide insight into the patterns of genetic diversity of saglin and laminin, and we discuss these findings in relation to the potential development of these molecules as vaccine targets.
Department of Entomology, Cornell University, Ithaca, NY, USA. j.crawford@berkeley.edu
Jacob E
JE
Crawford
Susan M
SM
Rottschaefer
Boubacar
B
Coulibaly
Madjou
M
Sacko
Oumou
O
Niaré
Michelle M
MM
Riehle
Sékou F
SF
Traore
Kenneth D
KD
Vernick
Brian P
BP
Lazzaro
D000818:Animals; D000852:Anopheles / Q000235:genetics*; D005260:Female; D019476:Insect Proteins / Q000235:genetics*; D007797:Laminin / Q000235:genetics; D008288:Malaria / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000494:pharmacology*; D012471:Salivary Proteins and Peptides / Q000235:genetics; D012641:Selection, Genetic / Q000235:genetics*; D013045:Species Specificity
D019476:Insect Proteins; D007797:Laminin; D017780:Malaria Vaccines; D012471:Salivary Proteins and Peptides; C535222:saglin protein, Anopheles gambiae; C058783:laminin beta2