The Orthologue of the Fruitfly Sex Behaviour Gene Fruitless in the Mosquito Aedes aegypti: Evolution of Genomic Organisation and Alternative Splicing

Abstract

In Drosophila melanogaster the doublesex (dsx) and fruitless (fru) regulatory genes act at the bottom of the somatic sex determination pathway. Both are regulated via alternative splicing by an upstream female-specific TRA/TRA-2 complex, recognizing a common cis element. dsx controls somatic sexual differentiation of non-neural as well as of neural tissues. fru, on the other hand, expresses male-specific functions only in neural system where it is required to built the neural circuits underlying proper courtship behaviour. In the mosquito Aedes aegypti sex determination is different from Drosophila. The key male determiner M, which is located on one of a pair of homomorphic sex chromosomes, controls sex-specific splicing of the mosquito dsx orthologue. In this study we report the genomic organization and expression of the fru homologue in Ae. aegypti (Aeafru). We found that it is sex-specifically spliced suggesting that it is also under the control of the sex determination pathway. Comparative analyses between the Aeafru and Anopheles gambiae fru (Angfru) genomic loci revealed partial conservation of exon organization and extensive divergence of intron lengths. We find that Aeadsx and Aeafru share novel cis splicing regulatory elements conserved in the alternatively spliced regions. We propose that in Aedes aegypti sex-specific splicing of dsx and fru is most likely under the control of splicing regulatory factors which are different from TRA and TRA-2 found in other dipteran insects and discuss the potential use of fru and dsx for developing new genetic strategies in vector control.

Phylogenetic Distribution and Evolutionary Dynamics of the Sex Determination Genes doublesex and transformer in Insects

“…Under the assumption of a unique transformer recruitment into the sex determination cascade at the basis of the holometabolous insects, secondary loss of transformer must have occurred on at least 2 occasions based on current studies: in the Lepidoptera [Mita et al, 2004] and the basal Diptera [Salvemini et al, 2013]. We found evidence for 2 additional possible losses, i.e.…”

“…An interesting pattern of transformer distribution emerges in the Diptera, where recent studies have suggested it to be absent in mosquitoes, which form a basal dipteran lineage [Salvemini et al, 2013]. transformer is found in all more derived Brachycera species (references in table 1 ) including D. melanogaster , where it has lost its CAM domain ( fig.…”

The evolution of novelty in conserved genes; evidence of positive selection in the Drosophila fruitless gene is localised to alternatively spliced exons

“…Substitutions occurring within alternatively spliced genes are both more localised (mainly in those exons being alternatively spliced) and less conservative than those in genes that have been duplicated (Talavera et al, 2007). The gene fruitless (fru) is an alternatively spliced transcription factor that has been identified in a broad range of insect groups (Salvemini et al, 2010), including Orthoptera (Ustinova and Mayer, 2006;Boerjan et al, 2011), Blattodea (Clynen et al, 2011), Hymenoptera (Bertossa et al, 2009) and Diptera (Ryner et al, 1996;Gailey et al, 2006;Salvemini et al, 2009;Sobrinho and de Brito, 2010;Salvemini et al, 2013). fru is a pleiotropic gene with at least two major functions: one that controls male sexual behaviour and another that is essential for viability in both sexes.…”

Conserved Domains in the Transformer Protein Act Complementary to Regulate Sex-Specific Splicing of Its Own Pre-mRNA

“…In Drosophila , TRA forms a complex with TRA-2 (and one or more SR proteins) to bind to the dsxREs located within the female-specific exon of dsx Maniatis, 1995, 1996]. It has been found that the TRA-2 proteins in M. domestica and C. capitata are required for female-specific splicing of tra pre-mRNAs [Burghardt et al, 2005;Hediger et al, 2010;Salvemini et al, 2013]. From these findings, it is postulated that MdTRA interacts with its own pre-mRNA through TRA-2, resulting in skipping of the male-specific exons [Hediger et al, 2010].…”

“…The presence of multiple sequences showing high homology to the dsxRE in the male-specific exons and in the surrounding introns may suggest that TRA interacts with its own pre-mRNA through TRA-2, resulting in skipping of the male-specific exons. It has been found that TRA-2 proteins in Musca domestica and C. capitata are required for female-specific splicing of tra pre-mRNAs [Burghardt et al, 2005;Hediger et al, 2010;Salvemini et al, 2013].…”