Hybrid male sterility and genome-wide misexpression of male reproductive proteases

Abstract

Hybrid male sterility is a common barrier to gene flow between species. Previous studies have posited a link between misregulation of spermatogenesis genes in interspecies hybrids and sterility. However, in the absence of fully fertile control hybrids, it is impossible to differentiate between misregulation associated with sterility vs. fast male gene regulatory evolution. Here, we differentiate between these two possibilities using a D. pseudoobscura species pair that experiences unidirectional hybrid sterility. We identify genes uniquely misexpressed in sterile hybrid male reproductive tracts via RNA-seq. The sterile male hybrids had more misregulated and more over or under expressed genes relative to parental species than the fertile male hybrids. Proteases were the only gene ontology class overrepresented among uniquely misexpressed genes, with four located within a previously identified hybrid male sterility locus. This result highlights the potential role of a previously unexplored class of genes in interspecific hybrid male sterility and speciation.

Hybrid sterility and evolution in Hawaiian Drosophila: differential gene and allele-specific expression analysis of backcross males

“…We found overwhelmingly more cis-divergent genes than trans-divergent genes in all BC groups. This result is consistent with those from other Drosophila, including closely related Drosophila p. pseudoobscura and D. p. bogotana (Gomes and Civetta, 2015), as well as more distantly related D. melanogaster and D. simulans (Wittkopp et al, 2004(Wittkopp et al, , 2008. A review of regulatory experiments by Bell et al (2013) concludes that generally cis-regulatory changes account for more divergent expression between more genetically divergent parents (for example, interspecific) than trans-effects that account for a higher proportion of variation in gene expression between less divergent parents (for example, intraspecific).…”

“…HMS is an important post-zygotic reproductive isolating mechanism in many eukaryotic organisms, but only recently has genome-wide gene expression analysis been used to investigate the full suite of genes involved in the expression of this complex trait (Gomes and Civetta, 2015). Here we analyze the differential gene expression and allelespecific expression (ASE) of testis-level fertility in BC males between two closely related endemic Hawaiian Drosophila species in the picture-wing clade under planitibia group and IVβ subgroup, Drosophila planitibia and Drosophila silvestris (Spieth, 1986).…”

Misregulation of Gene Expression and Sterility in Interspecies Hybrids: Causal Links and Alternative Hypotheses

“…One possibility is that the expression of X-linked genes themselves is disrupted in sterile hybrid males. Two independent genome-wide assays, one using sperm-specific microarrays to compare gene misregulation in hybrids between species of the simulans clade (Moehring et al 2006) and a more recent RNA sequencing survey of male reproductive gene expression in hybrids between Drosophila pseudoobscura pseudoobscura and Drosophila pseudoobscura bogotana (Gomes and Civetta 2015), revealed no evidence of any significant representation of misregulated X-linked genes.…”

“…It could simply be driven by few transcription factors of large effect, or by a particular subset of transcription factors regulating specific male reproductive gene expression. A potentially disproportional effect of X-linked transregulatory gene divergence in driving target genes' misregulation in hybrids was hinted in a previous transcriptomic scan, where eight out of ten autosomal genes with the largest reversal in allelic expression between hybrids favored the allele matching the X-chromosome genotype (Gomes and Civetta 2015).…”

“…It is therefore possible that these amino acid differences might result in different abilities of the protein to bind target DNA sites and regulate gene expression. It will be desirable to test whether Ovd binds upstream of any of the proteolytic and other genes found to be specifically misregulated in D. p. bogotana x D. p. pseudoobscura male sterile hybrids (Gomes and Civetta 2015). Out of the 21 sterile hybrid-specific misregulated proteases, 17 have at least one Adf-1 transcription binding site (a putative MADF target) somewhere between -500 and ?100 bp of their transcription start site (PROMO: http://alggen.lsi.upc.es/cgi-bin/promo_v3/promo/promoinit.…”