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

Abstract

There has been much debate concerning whether cis-regulatory or coding changes are more likely to produce evolutionary innovation or adaptation in gene function, but an additional complication is that some genes can dramatically diverge through alternative splicing, increasing the diversity of gene function within a locus. The fruitless gene is a major transcription factor with a wide range of pleiotropic functions, including a fundamental conserved role in sexual differentiation, species-specific morphology and an important influence on male sexual behaviour. Here, we examine the structure of fruitless in multiple species of Drosophila, and determine the patterns of selective constraint acting across the coding region. We found that the pattern of selection, estimated from the ratio of non-synonymous to synonymous substitutions, varied considerably across the gene, with most regions of the gene evolutionarily conserved but with several regions showing evidence of divergence as a result of positive selection. The regions that showed evidence of positive selection were found to be localised to relatively consistent regions across multiple speciation events, and are associated with alternative splicing. Alternative splicing may thus provide a route to gene diversification in key regulatory loci.

Fruitless isoforms and target genes specify the sexually dimorphic nervous system underlyingDrosophilareproductive behavior

“…The appearance and disappearance of fru C 2 H 2 zinc-finger domains through presumably a combination of exon duplication and/or loss, enables a single gene to diversify its functions, while ensuring its essential functions are maintained. Interestingly, a recent finding by Parker et al, 2014 34 showed that the fru A C 2 H 2 zinc-finger containing exon is under strong positive selection within the Drosophila species, suggesting changes in this exon may contribute to speciation, while the other zinc-finger exons fru B and fru C are highly conserved.…”

The locus of sexual selection: moving sexual selection studies into the post‐genomics era

“…One potential exception is when sex‐specific alternatively spliced gene transcripts show differing signatures of selection. Such a case has recently been described for fruitless in Drosophila and suggests that male functions have been under stronger divergent selection, most likely due to sexually dimorphic selection pressures (Parker et al ., ).…”

A non-coding indel polymorphism in thefruitlessgene ofDrosophila melanogasterexhibits antagonistically pleiotropic fitness effects

“…CC-BY-ND 4.0 International license perpetuity. It is made available under a preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in The copyright holder for this this version posted December 2, 2020. ; https://doi.org/10.1101/2020.12.01.406447 doi: bioRxiv preprint that is evident at the larger phylogenetic level, fru also exhibits evidence of positive selection [32]. In line with this evidence for micro-evolutionary dynamics, we identify here a polymorphism within the 5' non-coding region of the fru gene, which consists of a polymorphic indel and associated SNPs that segregate at relatively stable frequencies across worldwide populations of D. melanogaster.…”