Extensive Genetic Differentiation between Homomorphic Sex Chromosomes in the Mosquito Vector, Aedes aegypti

Abstract

Mechanisms and evolutionary dynamics of sex-determination systems are of particular interest in insect vectors of human pathogens like mosquitoes because novel control strategies aim to convert pathogen-transmitting females into nonbiting males, or rely on accurate sexing for the release of sterile males. In Aedes aegypti, the main vector of dengue and Zika viruses, sex determination is governed by a dominant male-determining locus, previously thought to reside within a small, nonrecombining, sex-determining region (SDR) of an otherwise homomorphic sex chromosome. Here, we provide evidence that sex chromosomes in Ae. aegypti are genetically differentiated between males and females over a region much larger than the SDR. Our linkage mapping intercrosses failed to detect recombination between X and Y chromosomes over a 123-Mbp region (40% of their physical length) containing the SDR. This region of reduced male recombination overlapped with a smaller 63-Mbp region (20% of the physical length of the sex chromosomes) displaying high male–female genetic differentiation in unrelated wild populations from Brazil and Australia and in a reference laboratory strain originating from Africa. In addition, the sex-differentiated genomic region was associated with a significant excess of male-to-female heterozygosity and contained a small cluster of loci consistent with Y-specific null alleles. We demonstrate that genetic differentiation between sex chromosomes is sufficient to assign individuals to their correct sex with high accuracy. We also show how data on allele frequency differences between sexes can be used to estimate linkage disequilibrium between loci and the sex-determining locus. Our discovery of large-scale genetic differentiation between sex chromosomes in Ae. aegypti lays a new foundation for mapping and population genomic studies, as well as for mosquito control strategies targeting the sex-determination pathway.

Alternative patterns of sex chromosome differentiation in Aedes aegypti (L)

“…Interestingly, Aaa had a distinct cluster of high inter-sex F ST genes on chromosome 1, with a few in distal locations ( n = 171). This region overlaps a similar region of high inter-sex F ST reported for the Liverpool Aaa strain [ 28 ]. This is consistent with retention of the sex locus in Aaa, with a cluster of inter-sex F ST genes proximal to nix (Fig.…”

“…SenAae had high inter-sex F ST genes across most of the chromosome ( n = 1233). This pattern is consistent with extensive chromosome length X-Y differentiation, which is different from findings of other aedine populations [ 28 ]. The high level of reported SenAae genetic diversity may have contributed to the chromosome-wide pattern [ 26 , 27 ], as mosquito pools rather than individuals were evaluated in this study.…”

“…Therefore the over-arching goal of this study was to extend our earlier study [ 27 ] and use population genomics analyses of SenAae and Aaa to characterize sex-specific allele frequency differences. Our hypothesis was that genes with high sex-specific or inter-sex F ST values would be located proximal to the M locus on chromosome 1 [ 28 ]. We used orthology information to predict whether these genes would be involved in in sex determination, reproduction and/or sexual dimorphic traits.…”

The queenslandensis and the type Form of the Dengue Fever Mosquito (Aedes aegypti L.) Are Genomically Indistinguishable

“…This was done to compare the extent of genetic structuring within and among samples at a regional and global scale. Sexing of the larval samples from Brazil and Vietnam could not be done based on the external morphological features, so we employed a genetic sexing method based on the presence/absence of the male-specific RAD tags [28]. All 119 individuals were included in the creation of the RAD tag catalogues using the default Stacks parameters in the maximum likelihood model of SNP and genotype calling.…”

A mutant variant of Nix gene on γ-irradiated Aedes aegypti as a male-determination factor

“…aegypti. This gene is located at the M locus on chromosome 1 (denoted 1.q.2.1), meaning it is located on chromosome 1, arm q, region 2 and band 1 as shown in Figure 1 (Hall et al 2015;Fontaine et al 2017). Gene mutation in the Nix gene can cause damage to the structure and function of the Nix protein.…”