Anopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 million people and causes more than 1 million deaths each year. Tenfold shotgun sequence coverage was obtained from the PEST strain of A. gambiae and assembled into scaffolds that span 278 million base pairs. A total of 91% of the genome was organized in 303 scaffolds; the largest scaffold was 23.1 million base pairs. There was substantial genetic variation within this strain, and the apparent existence of two haplotypes of approximately equal frequency (“dual haplotypes”) in a substantial fraction of the genome likely reflects the outbred nature of the PEST strain. The sequence produced a conservative inference of more than 400,000 single-nucleotide polymorphisms that showed a markedly bimodal density distribution. Analysis of the genome sequence revealed strong evidence for about 14,000 protein-encoding transcripts. Prominent expansions in specific families of proteins likely involved in cell adhesion and immunity were noted. An expressed sequence tag analysis of genes regulated by blood feeding provided insights into the physiological adaptations of a hematophagous insect.

Speciation in the Anopheles gambiae complex is reviewed and discussed with emphasis on the patterns of chromosomal differentiation, particularly at the intraspecific level. The significance of inversion polymorphism in gambiae and arabiensis (the two species of greatest medical importance) is evaluated with reference to recent field investigations carried out in Nigeria. In both sibling species some of the inversions show clinical geographical changes in frequencies, with evident correlations with climatic conditions and vegetation zones. Microgeographical variations in species distribution and in intraspecific inversion frequencies are also present, which appear mostly related to man-made environmental contrasts. Parallel indoor-/outdoor collections of samples from polymorphic populations of arabiensis and gambiae show that adult mosquitoes carrying certain inversion karyotypes do not distribute at random in relation to the human environment, being significantly more frequent in outdoor than in indoor samples, or vice-versa. Optimal habitat choice appears to be involved in such variations of indoor resting behaviour, since the chromosomal types carried by less endophilic individuals are those more adapted to humid climates, i.e. those which tend to avoid the higher nocturnal saturation deficit of the indoor environment. This phenomenon, producing non-uniform exposure of the vector population to residual insecticides sprayed in houses, might explain the mediocrity of the results of malaria control projects based on house-spraying against endophilic vectors in the African savannas.

Field-collected specimens of all known taxa in the Anopheles gambiae complex were analyzed on the basis of chromosome inversions with reference to a standard polytene chromosome map. The phylogenetic relationships among the seven described species in the complex could be inferred from the distribution of fixed inversions. Nonrandom patterns of inversion distribution were observed and, particularly on chromosome arm 2R, provided evidence for genetically distinct populations in A. gambiae, A. arabiensis, and A. melas. In A. gambiae from Mali, stable genetic differentiation was observed even in populations living in the same region, suggesting a process of incipient speciation which is being confirmed by studies with molecular markers. The possible role of chromosome differentiation in speciation of the A. gambiae complex and in the emergence of distinct chromosomal forms within the nominal species is discussed in relation to human malaria.

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Chromosome rearrangements (such as inversions, fusions, and fissions) may play significant roles in the speciation between parapatric (contiguous) or partly sympatric (geographically overlapping) populations. According to the ''hybrid-dysfunction'' model, speciation occurs because hybrids with heterozygous chromosome rearrangements produce dysfunctional gametes and thus have low reproductive fitness. Natural selection will, therefore, promote mutations that reduce the probability of intercrossing between populations carrying different rearrangements and thus promote their reproductive isolation. This model encounters a disabling difficulty: namely, how to account for the spread in a population of a chromosome rearrangement after it first arises as a mutation in a single individual. The ''suppressed-recombination'' model of speciation points out that chromosome rearrangements act as a genetic filter between populations. Mutations associated with the rearranged chromosomes cannot flow from one to another population, whereas genetic exchange will freely occur between colinear chromosomes. Mutations adaptive to local conditions will, therefore, accumulate differentially in the protected chromosome regions so that parapatric or partially sympatric populations will genetically differentiate, eventually evolving into different species. The speciation model of suppressed recombination has recently been tested by gene and DNA sequence comparisons between humans and chimpanzees, between Drosophila species, and between species related to Anopheles gambiae, the vector of malignant malaria in Africa.genetic divergence ͉ chromosomal rearrangements ͉ human speciation ͉ Drosophila speciation ͉ Anopheles speciation