Evidence is mounting that the evolution of gene expression plays a major role in adaptation and speciation. Understanding the evolution of gene regulatory regions is indeed an essential step in linking genotypes and phenotypes and in understanding the molecular mechanisms underlying evolutionary change. The common view is that expression traits (protein folding, expression timing, tissue localization and concentration) are under natural selection at the individual level. Here, we use a theoretical approach to show that, in addition, in diploid organisms, enhancer strength (i.e., the ability of enhancers to activate transcription) may increase in a runaway process due to competition for expression between homologous enhancer alleles. These alleles may be viewed as self-promoting genetic elements, as they spread without conferring a benefit at the individual level. They gain a selective advantage by getting associated to better genetic backgrounds: deleterious mutations are more efficiently purged when linked to stronger enhancers. This process, which has been entirely overlooked so far, may help understand the observed overrepresentation of cis-acting regulatory changes in between-species phenotypic differences, and sheds a new light on investigating the contribution of gene expression evolution to adaptation.

BackgroundIn the context of generalization of insecticide resistance, the hypothesis that insecticide resistance has a positive impact on the capacity of mosquitoes to transmit malaria constitutes a hindrance for malaria elimination. The aim of this study was to investigated populations of Anopheles coluzzii and Anopheles gambiae S molecular form to assess whether different genotypes at the kdr locus are responsible for different susceptibility to Plasmodium falciparum infection.MethodsF3 progeny of An. gambiae s.l. collected in Dielmo were infected by direct membrane feeding with P. falciparum gametocyte-containing blood sampled from volunteer patients. The presence of oocysts was determined by light microscopy after seven days, and the presence of sporozoites by ELISA after 14 days. Mosquito species and molecular forms were identified by PCR. Generalized linear models were performed using the R software to test the effect of explanatory variables including the genotype at the kdr locus on infection rate and density.ResultsThe odds of being infected with oocysts and sporozoites were greater in RS and RR groups than in SS groups (χ2 = 42.8, df = 1, P(>χ2) = 6.1e-11). The density of infection was also dependent on genotype, with RR and RS genotypes showing denser infection than SS genotypes. Pairwise comparisons of oocyst number and absorbance indicated sometime a small betwen species (i.e. between An. gambiae S form, and An. coluzzii), but the effect of genotype was much more important.ConclusionThe presence of the resistance allele at the kdr locus increases susceptibility to Plasmodium not only at the oocyst stage but also at the sporozoite stage in non-genetically modified wild mosquitoes. These results have significant implications and should be taken into account in the development of strategies for malaria control.