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Speciation and changes in male gene expression in Drosophila

Publication: Genome
30 July 2020


It has long been acknowledged that changes in the regulation of gene expression may account for major organismal differences. However, we still do not fully understand how changes in gene expression evolve and how do such changes influence organisms’ differences. We are even less aware of the impact such changes might have in restricting gene flow between species. Here, we focus on studies of gene expression and speciation in the Drosophila model. We review studies that have identified gene interactions in post-mating reproductive isolation and speciation, particularly those that modulate male gene expression. We also address studies that have experimentally manipulated changes in gene expression to test their effect in post-mating reproductive isolation. We highlight the need for a more in-depth analysis of the role of selection causing disrupted gene expression of such candidate genes in sterile/inviable hybrids. Moreover, we discuss the relevance to incorporate more routinely assays that simultaneously evaluate the potential effects of environmental factors and genetic background in modulating plastic responses in male genes and their potential role in speciation.


Il est reconnu depuis longtemps que des changements dans le niveau d’expression génique peuvent entraîner des différences importantes chez les organismes. Cependant, il n’est pas encore pleinement compris comment les changements d’expression génique évoluent et comment de tels changements influencent les différences entre organismes. Encore moins de choses sont connues sur l’impact que de tels changements peuvent avoir sur la restriction des flux géniques entre espèces. Dans ce travail, les auteurs se penchent sur des études portant sur l’expression génique et la spéciation chez l’espèce modèle Drosophila. Les auteurs passent en revue des études qui ont identifié des interactions géniques avec l’isolement reproductif post-accouplement et la spéciation, particulièrement celles qui modulent l’expression génique chez les mâles. Les auteurs s’intéressent également à des études qui ont modifié expérimentalement le niveau d’expression génique pour en mesurer l’effet sur l’isolement reproductif post-accouplement. Les auteurs font ressortir la nécessité d’études plus approfondies du rôle de la sélection causant une perte d’expression de gènes candidats chez des hybrides stériles ou non-viables. De plus, les auteurs discutent de la pertinence d’incorporer de manière plus routinière des essais qui mesurent simultanément les effets potentiels des facteurs environnementaux et du fond génétique dans la modulation de la réponse plastique des gènes mâles et de leur rôle potentiel dans la spéciation. [Traduit par la Rédaction]


In 1975, King and Wilson used data from protein sequence comparisons and allele frequency of polypeptide products to show high protein similarity between humans and chimpanzee despite substantial morphological disparity between the two species. The authors proceeded to suggest that changes in regulation of gene expression should account for major organismal differences (King and Wilson 1975). In the era of genomes, we are still in our infancy with regards to understanding how changes in expression of information contained in DNA influences differences between phenotypes of organisms and more so on how they contribute to speciation. This lack of information is surprising given that the vast majority of the genome is noncoding and possesses a myriad of DNA sequences, like promoters and enhancers, that can influence traits by regulating the expression of genes. For example, approximately 80% of the Drosophila melanogaster euchromatic genome is noncoding (Halligan and Keightley 2006), while this ratio increases up to 98% in human (Birney et al. 2007), providing a large source of DNA targets that could be related to regulation of gene expression.
Gene regulation involves interactions between two (or more) genes. The speciation literature has long acknowledged the importance of gene interactions in the establishment of post-mating reproductive isolation barriers (Perez and Wu 1995; Johnson 2000; Orr and Irving 2001; Tao et al. 2003; Sawamura et al. 2004; Chang and Noor 2007; Tang and Presgraves 2009; Chang et al. 2010; Phadnis 2011). These empirical studies have highlighted that the effect of major “speciation” genes is dependent on genetic background and involves complex genetic interactions. The important role played by negative gene interactions during the early stages of divergence and the decline of hybrid fitness is illustrated in a widely popular model known as the Bateson–Dobzhansky–Muller (BDM) model (reviewed in Orr 1996). This model recognizes that when two diverged populations hybridize, divergent alleles from the two parental types are brought together in heterozygosity. The model is Mendelian in its explanation of genetic incompatibilities arising from an allelic change in a locus in one population (A to a) and another change in a different locus (B to b) in another population. These two new alleles are assumed to be incompatible when they meet in the same genome (a and b) leading to deleterious effects in the hybrids. The sum of such incompatibilities across loci in a hybrid genome can cause hybrid inviability or sterility. More recent models have acknowledged the relevance of positive epistatic interactions, included a consideration of processes driving the fixation of new mutations within populations, and evaluated the network structure within which gene interactions might occur. The major difference in these models in relation to speciation is that they incorporate the importance of the disruption in hybrids of the positive epistatic interactions built within populations, rather than solely focusing on negative epistatic interactions appearing for the first time in hybrids (Dagilis et al. 2019).
While many studies have identified the role of epistatic interactions, only a very limited number of actual or likely interacting genes associated with hybrid incompatibilities have been identified. The best understood system is hybrid male lethality in crosses between D. melanogaster and D. simulans. The cross produces sterile hybrid females and no males. Male lethality has been shown to be rescuable by the Lethal hybrid rescue (Lhr) mutation in D. simulans and also by the Hybrid male rescue (Hmr) mutation in D. melanogaster (Inoue and Watanabe 1979; Barbash et al. 2000, 2003). These two genes interact with each other, but their interaction is not enough to cause hybrid lethality (Brideau et al. 2006). Indeed, a three loci interaction was originally suggested in early mapping studies (Pontecorvo 1943), with a recent genomic screen identifying an actual third gene (gfzf); the removal of the D. simulans allele leading to the rescue of male viability (Phadnis et al. 2015). Interestingly, GFZF does not physically interact with the other two proteins but exerts its effect through a different form of genetic interaction with Hmr. gfzf is a transcriptional co-activator (Baumann et al. 2017) and while in both species HMR and GFZF do not overlap in binding sites; in hybrids, HMR mislocalizes to sites normally occupied by GFZF and this mislocalization is rescuable by the reduction of expression of the gfzf allele (Cooper et al. 2019). This gene network system nicely illustrates the relevance of actual gene–gene interactions and the role of differences in gene expression on the manifestation of the speciation phenotype.
Evidence for male-specific regulatory elements that could promote hybrid dysfunction is scarce, but previously characterized major speciation genes such as Odysseus (Ting et al. 1998, 2004) and Overdrive (Phadnis and Orr 2009) are interesting targets as these genes have possible regulatory functions and are rapidly evolving between closely related species. Moreover, the fact that both genes are localized in the X chromosome makes them instances of specific X-chromosome genes influencing male gene expression that can be linked to speciation. Odysseus (OdsH) is needed for proper sperm production in D. melanogaster, and its abundance and localization during spermatogenesis is different between D. simulans and D. mauritiana (Bayes and Malik 2009; Cheng et al. 2012). The protein has a homeobox binding motif and it exerts its sterilizing effect by differentially binding heterochromatin (Ting et al. 1998; Sun et al. 2004; Bayes and Malik 2009). Overdrive (Ovd) is an interesting major speciation gene as its protein contains a DNA binding domain making it potentially capable of targeting and regulating the expression of other genes (Phadnis and Orr 2009). In addition, some potential male gene targets of Ovd that are misregulated in sterile hybrids between subspecies D. p. bogotana and D. p. pseudoobscura have been recently identified (Alhazmi et al. 2019; Go et al. 2019).
In this review, we address the potential role of male-expressed gene regulation in speciation by focusing primarily on studies that have used Drosophila, the focal organism covered in this issue. We specifically devote our efforts to review recent progress that (i) has identified rapid evolution of male-expressed genes and the putative role of their expression changes in speciation, (ii) has discussed the role of divergence in male gene regulation through directional selection driving different adaptive responses in newly evolved species versus stabilizing selection favouring compensatory mutations within species that are disrupted in hybrids, (iii) has summarized sex chromosome contribution to male gene regulation, and (iv) has discussed plasticity of male genes depending on genetic background and environmental changes and their potential implication to speciation. Overall, we aim to emphasize the importance of male genes in post-mating reproductive isolation through hybrid incompatibilities and ultimately speciation.

Faster expression divergence of male genes

Genome-wide analyses have shown that gene regulatory changes and adaptive evolution of gene expression is common among species of Drosophila (Rifkin et al. 2003; Graze et al. 2009; Coolon et al. 2014; Nourmohammad et al. 2017). While changes in expression of many different genes can contribute to speciation, male reproduction genes are most likely major contributors to speciation for at least three reasons: (i) sexual selection and sexual conflict can lead to rapid gene sequence divergence in male genes (Swanson and Vacquier 2002; Clark et al. 2006; Haerty et al. 2007), (ii) early stage breakdowns to gene flow between species predominantly involves disruptions in male reproductive hybrid fitness attributable male reproduction genes (Singh 1990, 1999; Wu and Davis 1993), and (iii) disruption of male gene expression in male sterile hybrids is likely to contribute to the establishment of reproductive isolation (Gomes and Civetta 2015; Alhazmi et al. 2019; Go et al. 2019).
Comparative analyses of gene expression among species of Drosophila has shown that expression of male-biased genes (e.g., testis- and accessory gland-specific genes) diverges faster than female-biased genes and nonsex-biased genes (Meiklejohn et al. 2003; Ranz et al. 2003a; Nuzhdin et al. 2004; Jagadeeshan and Singh 2005; Zhang et al. 2007; Grath et al. 2009; Jiang and Machado 2009; Assis et al. 2012; Nourmohammad et al. 2017; Llopart et al. 2018). One of these studies showed that there is also more variation in expression within species if the gene is male biased in that species (Zhang et al. 2007). Moreover, male-biased genes show high levels of gene expression variation between different populations of D. melanogaster (Hutter et al. 2008; Kohn et al. 2008) and latitudinal clines of D. serrata (Allen et al. 2017, 2018). Divergent gene regulatory mechanisms causing gene expression divergence could be driven by different selective pressure in different species (Mack and Nachman 2017; Signor and Nuzhdin 2018). Interestingly, DNA sequence evolution of genes expressed primarily or uniquely in the male reproductive tract tissue such as testis-specific genes, male seminal fluid, and spermatogenesis genes have been shown to evolve faster and show positive selection in lineages of Drosophila (Haerty et al. 2007).
The rapid evolution of male genes such as those with roles in sperm development could be intuitively linked to hybrid disfunction that often involves male sterility. In fact, studies that surveyed differences in gene expression between species and F1 fertile versus sterile hybrids, or the use of crossing designs that create hybrids in which the sterility phenotype could be manipulated, have in general found evidence for the rapid evolution of regulation of expression of sperm production genes and an overall enrichment for misregulation of spermatogenesis genes associated with sterility (Maside et al. 1998; Ting et al. 1998; Michalak and Noor 2003; Moehring et al. 2007; Ferguson et al. 2013; Gomes and Civetta 2014; Brill et al. 2016; Civetta 2016; Alhazmi et al. 2019) (Table 1). Despite possible uncertainties of effects unlinked to sterility, OdsH, a gene that functions in sperm production in young males but causes sterility in the hybrids between D. mauritiana and D. simulans (Table 1), has shown misregulation of expression in the sterile condition with accumulation of transcripts in the testes (Sun et al. 2004).
Table 1.
Table 1. Genes linked to speciation phenotypes in Drosophila.

Note: The list is not exhaustive as our review focuses on male gene expression changes and putative identified interactions in speciation. MRT, male reproductive tract; HMS, hybrid male sterility; CSP, conspecific sperm precedence.

D. mel (Drosophila melanogaster), D. sim (Drosophila simulans), D. mau (Drosophila mauritiana), D. p. pse (Drosophila pseudoobscura pseudoobscura), D. p. bog (Drosophila pseudoobscura bogotana), D. w. will (Drosophila willistoni willistoni), D. w. win (Drosophila willistoni winge), D. sil (Drosophila silvestris), D. pla (Drosophila planitibia).
FlyBase for molecular function in and InterPro for protein signatures/domains.
Seminal fluid protein (SFP)-coding genes have been shown to evolve under positive selection likely linked to post-mating sexual selection (Swanson et al. 2001; Kern et al. 2004; Wong et al. 2008; Civetta and Reimer 2014). This is also a very interesting group of genes as their rapid evolution often leads to a lack of orthology among more distantly related species of Drosophila (Haerty et al. 2007; Ahmed-Braimah et al. 2017). How sequence and expression changes in SFP genes might influence speciation is an open area of inquiry, given their rapid divergence. An early study suggesting their potential role in post-mating reproductive isolation comes from Fuyama (1983), who showed that stimulation of ovulation in D. suzukii females via transferred seminal fluid of males did not occur when males mated with D. pulchrella females. This caused an effective barrier to hybridization and highlighted the potential role of genetic divergence in seminal fluids in the establishment of post-mating reproductive barriers between species. Recently, the role played by specific SFP genes in speciation has been demonstrated by experimentally perturbing their expression. The study found that knock-down of two SFP genes AcpDE36 and CG9997 (Table 1), but not another seminal fluid gene Sex Peptide, affected conspecific sperm precedence (CSP) when sibling species of Drosophila mated (Castillo and Moyle 2014). CSP is a post-mating prezygotic barrier between species caused by the preference of females to utilize sperm from males of the same species as opposed to heterospecific sperm (Price et al. 2000). The potential role of other seminal fluid genes in CSP is unknown. SFP genes with known roles in sperm competition (sexual selection) are interesting candidates to test whether gene perturbation through knock down or knock out also contributes to reproductive isolation via CSP (speciation). Testing connections between sexual selection/conflict and speciation is particularly desired given that speciation driven by sexual selection has been proposed and challenged (Ritchie 2007; Kraaijeveld et al. 2011; Gavrilets 2014; Servedio and Bürger 2014).

Divergence in regulatory elements and the role of selection in speciation

Gene expression involves interactions between genetic elements that lead to the production of specific gene products (e.g., transcripts and proteins). Thus, gene expression is expected to be susceptible to incompatibilities arising when two divergent genomes come together in a hybrid. Typically, genetic elements that influence the expression of a gene can be partitioned into cis- and trans-regulatory elements. Cis-regulation is exerted by sequences that are proximal to the gene being regulated and can commonly be thought as promoter or promoter-proximal elements. Trans-regulation is exerted by diffusible products (e.g., proteins) that are not necessarily linked to the gene being regulated. Genome-wide studies of gene expression have identified more divergence between species in cis-regulatory elements than trans-regulatory elements, and their potential contribution to hybrid incompatibilities during the establishment of isolating barriers (Wittkopp et al. 2008; Coolon et al. 2014; Osada et al. 2017; Signor and Nuzhdin 2018). Besides the preponderance of cis over trans divergence, the decomposition of cis versus trans effects has also shown a large proportion of compensatory changes that contribute to maintain similar levels of gene expression in different species (Landry et al. 2005; Coolon et al. 2014). Given that adaptive evolution of gene expression is common in species (Ellegren and Parsch 2007; Parsch and Ellegren 2013), a key question to understanding speciation is as follows: what adaptive changes accumulate within different populations/species and how can these changes induce post-mating reproductive barriers through hybrid incompatibilities?
One possibility is that directional selection in male-expressed genes towards different adaptations in incipient species contributes to reproductive isolation by hybrid divergent genomes becoming incompatible. This is supported by the fact that, in general, the rate of protein-coding gene evolution and gene expression divergence correlates between species of Drosophila (Nuzhdin et al. 2004; Lemos et al. 2005), but more importantly that the correlation is significant between the rate of nonsynonymous substitutions leading to protein content change, a proxy of positive selection, and male gene expression but not by changes in neutrally evolving synonymous changes (Ranz et al. 2003b; Artieri et al. 2007). However, one caveat is that these correlation studies have been conducted with species pairs of the D. melanogaster group that have attained complete or nearly complete isolation. An alternative is that stabilizing selection working to maintain an optimal level of gene expression in different lineages might cause misregulation of gene expression in hybrids and cause dysfunction. Different deleterious mutations can disrupt the level of expression of a gene, but such effect can be compensated by mutations that work to restore levels of expression back to their norm. If different compensatory changes occur in different lineages, the result is a lack of divergence in gene expression between divergent populations or species but misregulation of expression in hybrids. In Drosophila, some genome-wide comparisons of expression that have teased apart how cis- and trans-regulatory elements influence the expression of genes have more often found that their effects work in opposite directions as expected under compensatory mechanisms to keep levels of expression within an adaptive norm (Landry et al. 2005; McManus et al. 2010; Takahasi et al. 2011). This is supportive of the hypothesis that gene expression evolves under a house of cards model of stabilizing selection (Hodgins-Davis et al. 2015). An interesting couple of studies using divergent populations of copepods has proposed that misexpression in hybrids of genes linked to metabolic pathways might work to buffer physiological hybrid dysfunction and possibly ameliorate fitness loss (Barreto et al. 2015, 2018).
Finally, it is also possible that gene duplication events leading to the relaxation of selective pressures in newly evolved genes could contribute to divergence in gene expression and possibly gene function (e.g., neo-functionalization). Many transcription factors are known to arise by gene duplication (Voordeckers et al. 2015), suggesting gene regulatory divergence can be widely driven by duplication events. According to a comprehensive genome-wide scale study by Wyman et al. (2012), duplicate pairs contain more male-biased genes than female-biased genes in Drosophila. There are, in D. melanogaster, specific examples that illustrate ancestral genes with broad or specific patterns of expression but newly evolved duplicates being male biased (Yanicostas et al. 1995; Bai et al. 2007; Belote and Zhong 2009; Li et al. 2009; Sirot et al. 2014). OdsH is particularly interesting as it is a duplicate of unc-4 that appears to have evolved towards a new, but dispensable, function within species, but able to exert a major role in species differentiation and speciation (Ting et al. 2004). The gene expression is severely affected in sterile male hybrids (Sun et al. 2004).

Sex chromosomes and male gene expression in speciation

It is common for reproductive isolation via hybrid dysfunction to occur mainly in the heterogametic sex, and it has been often linked to a major X-chromosome (or Z-) effect (Haldane 1922; Presgraves 2008). The role of sex chromosomes in hybrid dysfunction has been extensively covered elsewhere (Presgraves 2008; Coyne 2018). One interesting characteristic of the X chromosome is its fast rate of evolution, which likely facilitates its effect on hybrid male sterility (Llopart 2012; Llopart et al. 2018). This divergence is strongest for genes with male-biased expression (Baines et al. 2008; Meisel et al. 2009; Llopart et al. 2018), and recessive X alleles appear to have a significant contribution to misexpression in the hybrids and possibly sterility (Llopart et al. 2018). However, male-biased genes of flies are significantly underrepresented on the X chromosome (Parisi et al. 2003; Assis et al. 2012) and seminal fluid genes, as one major group of male-biased genes, are localized only in autosomes (Chapman 2001; Findlay et al. 2008). Nevertheless, the X chromosome contributes to autosomal male-biased gene regulation in this system (Meiklejohn et al. 2011; Kemkemer et al. 2014). This is likely because the faster X-gene expression divergence is not limited to faster cis-, but also involves rapid divergence of trans-diffusible regulatory elements, suggesting the capacity of the X chromosome to regulate both X-linked and autosomal gene expression (Coolon et al. 2015; Llopart et al. 2018). Hybrid male sterility clearly involves interactions between X-linked and autosomal factors, and specific targets have been identified (e.g., Nup genes; Tang and Presgraves 2009). We also have clear examples of male-expressed X-linked speciation genes, such as Ovd (Phadnis and Orr 2009; Phadnis 2011) and OdsH (Ting et al. 1998), that can cause hybrid dysfunction in Drosophila by modulating testes transcript production (Sun et al. 2004; Michalak and Ma 2008) or affecting the expression of specific autosomal testes gene targets (e.g., GA20504 and GA10921) (Alhazmi et al. 2019; Go et al. 2019) (Table 1). It is worth to note that unlike Drosophila, male-biased genes are enriched on the mammalian X chromosome (Wang et al. 2001). A comparison between humans and chimpanzees with respect to tissue-specific differences in expression levels and protein-coding sequences found X-linked genes expressed in testis showing significant expression changes as well as positive selection thus supporting a role for X chromosome male-biased genes in primates evolution (Khaitovich et al. 2005).
The contribution of the Y chromosome in speciation is less clear; nevertheless, there is suggestive evidence. For example, in contrast to other species of Drosophila, the X chromosome has only a small effect on hybrid male sterility between D. virilis and D. americana; however, the Y chromosome exerts a strong effect on hybrid male sterility (Sweigart 2010). An interesting characteristic of the Y chromosome is that it seems more likely to contribute to gene regulation via epigenetic mechanisms (Lemos et al. 2010), suggesting a possible environment-dependent role in speciation, such as heat-induced male sterility related with Y chromosome variation (Rohmer et al. 2004; David et al. 2005). While its role in male gene regulation has remained unclear, variation in the Y chromosome in D. melanogaster has been found to correlate with male-biased gene expression of autosomal and X-linked genes and contribute to divergence between D. melanogaster and D. simulans (Lemos et al. 2008).

Plasticity in male gene expression and speciation

Phenotypic plasticity, that is the ability of a genotype to produce different phenotypes depending on environmental conditions, is a central topic in evolution. Gene expression is sensitive to variation in physical environments (e.g., crowding, temperature) as well as genetic background (i.e., different genotypes respond in different ways to the same environment) (Pavey et al. 2010; Pfennig et al. 2010). It is therefore possible that differences in gene expression triggered by environmental changes might result in hybrid incompatibilities. Two lines of evidence offer some support for this hypothesis. First, models of speciation that incorporate genotype-by-environment interactions (GEI) have been shown to speed up the accumulation of BDM incompatibilities (Bordenstein and Drapeau 2001). Second, environmental changes have been shown to contribute to reproductive isolation in Drosophila by altering hybrid fitness. For example, the expressivity of hybrid inviability between D. melanogaster and its sibling species is influenced by temperature, and the temperature effect can also be modulated by the genotype of the parental strains (genome background) (Hutter and Ashburner 1987; Coyne et al. 1998; Miller and Matute 2017).
Plasticity in male ejaculate traits has been shown in Drosophila. For example, in D. melanogaster, the manipulation of larval density results in changes in size of the gland that produces seminal fluids as well as variable production and expenditure of SFPs (Bretman et al. 2016; Wigby et al. 2016). In studies where adult D. melanogaster male density was manipulated, complex transcriptomic responses and changes in expression of SFP genes were also identified (Fedorka et al. 2011; Mohorianu et al. 2017). We also know that social environment manipulations lead to plasticity of Drosophila sperm transfer (Garbaczewska et al. 2013). Previous studies have focused on genotypic response to environmental manipulation, but we lack knowledge on the role of genotypic background and environmental interactions in Drosophila. However, male gene expression in nematodes is sensitive to both environment and genotypic background and displays significant GEI affecting SFP expression (Patlar et al. 2019; Patlar and Ramm 2020). Considering that male-expressed genes, such as those producing SFP, often express condition dependent, one gap in our knowledge is the relationship between their variation in expression and plasticity in phenotypic output, particularly as it relates to reproductive isolation.
Ideally, whether the male-expressed genes contributing to reproductive isolation vary depending on environmental conditions and genetic background should be determined. In this context, male genes preventing hybridization between divergent populations via CSP can be important mediators of speciation (Civetta and Ranz 2019). For example, two genes known to function in sperm competition and CSP in Drosophila, i.e., Acp36DE and CG9997 (Table 1) (Castillo and Moyle 2014), might be plastic in their expression, and thus, their contribution to reproductive isolation among populations/species of Drosophila might be dependent on environmental conditions, genotypic differences, and genotype × environment interactions (GEI). Moving forward, tools such as the Drosophila Genetic Reference Panel of inbred lines offer an opportunity to simultaneously test the differential expression of candidates genes across genotypes and over different environments, as well as to phenotypically assay the effect of such changes on reproductive isolation phenotype (e.g., CSP). This approach should provide an opportunity to test GEI of male gene expression and associations with speciation phenotypes. In the long term, an avenue of inquiry pertains to testing the possibility that specific epigenetic changes might contribute to post-mating reproductive isolation. For example, some studies in plants have provided evidence to support the hypothesis that trans-generationally heritable epialleles can contribute to hybrid incompatibility (Durand et al. 2012; Lafon-Placette and Köhler 2015; Blevins et al. 2017).


Studies of gene expression divergence using Drosophila suggest that changes in regulation of gene expression can contribute to speciation and that male-expressed genes are likely to be important candidates driving post-mating reproductive isolation. Comparative genome-wide expression studies could not only reveal individual candidate genes but also identify important gene networks. Adaptive changes seem to be important during the evolution of gene regulation, but whether gene regulatory incompatibilities in hybrids are largely driven by the bringing together of interspecies divergent regulatory elements or by incompatibilities between different compensatory changes that might have independently evolved within species is still unclear. We believe teasing apart these possibilities will require work with focus on taxa in early stages of speciation. Finally, the context dependency of gene expression effects on reproductive phenotypes that could drive isolation between species is an area largely unexplored.


This work has been supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant to A.C.


Ahmed-Braimah Y.H., Unckless R.L., and Clark A.G. 2017. Evolutionary dynamics of male reproductive genes in the Drosophila virilis subgroup. Genes Genomes Genet. 7(9): 3145–3155.
Alhazmi D., Fudyk S.K., and Civetta A. 2019. Testes proteases expression and hybrid male sterility between subspecies of Drosophila pseudoobscura. Genes Genomes Genet. 9(4): 1065–1074.
Allen S.L., Bonduriansky R., Sgro C.M., and Chenoweth S.F. 2017. Sex-biased transcriptome divergence along a latitudinal gradient. Mol. Ecol. 26(5): 1256–1272.
Allen S.L., Bonduriansky R., and Chenoweth S.F. 2018. Genetic constraints on microevolutionary divergence of sex-biased gene expression. Philos. Trans. R. Soc. B Biol. Sci. 373(1757): 20170427.
Artieri C.G., Haerty W., and Singh R.S. 2007. Association between levels of coding sequence divergence and gene misregulation in Drosophila male hybrids. J. Mol. Evol. 65(6): 697–704.
Assis R., Zhou Q., and Bachtrog D. 2012. Sex-biased transcriptome evolution in Drosophila. Genome Biol. Evol. 4(11): 1189–1200.
Bai Y., Casola C., Feschotte C., and Betrán E. 2007. Comparative genomics reveals a constant rate of origination and convergent acquisition of functional retrogenes in Drosophila. Genome Biol. 8(1): R11.
Baines J.F., Sawyer S.A., Hartl D.L., and Parsch J. 2008. Effects of X-linkage and sex-biased gene expression on the rate of adaptive protein evolution in Drosophila. Mol. Biol. Evol. 25(8): 1639–1650.
Barbash D.A., Roote J., and Ashburner M. 2000. The Drosophila melanogaster hybrid male rescue gene causes inviability in male and female species hybrids. Genetics, 154(4): 1747–1771.
Barbash D.A., Siino D.F., Tarone A.M., and Roote J. 2003. A rapidly evolving MYB-related protein causes species isolation in Drosophila. Proc. Natl. Acad. Sci. U.S.A. 100(9): 5302–5307.
Barreto F.S., Pereira R.J., and Burton R.S. 2015. Hybrid dysfunction and physiological compensation in gene expression. Mol. Biol. Evol. 32(3): 613–622.
Barreto F.S., Watson E.T., Lima T.G., Willett C.S., Edmands S., Li W., and Burton R.S. 2018. Genomic signatures of mitonuclear coevolution across populations of Tigriopus californicus. Nat. Ecol. Evol. 2(8): 1250–1257.
Baumann D.G., Dai M.-S., Lu H., and Gilmour D.S. 2017. GFZF, a glutathione S-transferase protein implicated in cell cycle regulation and hybrid inviability, is a transcriptional coactivator. Mol. Cell. Biol. 38(4): e00476–17.
Bayes J.J. and Malik H.S. 2009. Altered heterochromatin binding by a hybrid sterility protein in Drosophila sibling species. Science, 326(5959): 1538–1541.
Belote J.M. and Zhong L. 2009. Duplicated proteasome subunit genes in Drosophila and their roles in spermatogenesis. Heredity, 103(1): 23–31.
Birney E., Stamatoyannopoulos J.A., Dutta A., Guigó R., Gingeras T.R., Margulies E.H., et al. 2007. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature, 447(7146): 799–816.
Blevins T., Wang J., Pflieger D., Pontvianne F., and Pikaard C.S. 2017. Hybrid incompatibility caused by an epiallele. Proc. Natl. Acad. Sci. U.S.A. 114(14): 3702–3707.
Bordenstein S.R. and Drapeau M.D. 2001. Genotype-by-environment interaction and the Dobzhansky-Muller model of postzygotic isolation. J. Evol. Biol. 14(3): 490–501.
Bretman A., Fricke C., Westmancoat J.D., and Chapman T. 2016. Effect of competitive cues on reproductive morphology and behavioral plasticity in male fruitflies. Behav. Ecol. 27(2): 452–461.
Brideau N.J., Flores H.A., Wang J., Maheshwari S., Wang X., and Barbash D.A. 2006. Two Dobzhansky-Muller genes interact to cause hybrid lethality in Drosophila. Science, 314(5803): 1292–1295.
Brill E., Kang L., Michalak K., Michalak P., and Price D.K. 2016. Hybrid sterility and evolution in Hawaiian Drosophila: differential gene and allele-specific expression analysis of backcross males. Heredity, 117(2): 100–108.
Castillo D.M. and Moyle L.C. 2014. Intraspecific sperm competition genes enforce post-mating species barriers in Drosophila. Proc. R. Soc. B Biol. Sci. 281(1797): 20142050.
Chang A.S. and Noor M.A.F. 2007. The genetics of hybrid male sterility between the allopatric species pair Drosophila persimilis and D. pseudoobscura bogotana: dominant sterility alleles in collinear autosomal regions. Genetics, 176(1): 343–349.
Chang A.S., Bennett S.M., and Noor M.A.F. 2010. Epistasis among Drosophila persimilis factors conferring hybrid male sterility with D. pseudoobscura bogotana. PLoS ONE, 5(10): e15377.
Chapman T. 2001. Seminal fluid-mediated fitness traits in Drosophila. Heredity, 87(Pt. 5): 511–521.
Cheng Y.J., Fang S., Tsaur S.C., Chen Y.L., Fu H.W., Patel N.H., and Ting C.T. 2012. Reduction of germ cells in the Odysseus null mutant causes male fertility defect in Drosophila melanogaster. Genes Genet. Syst. 87(4): 273–276.
Civetta A. 2016. Misregulation of gene expression and sterility in interspecies hybrids: Causal links and alternative hypotheses. J. Mol. Evol. 82(4–5): 176–182.
Civetta A. and Ranz J.M. 2019. Genetic factors influencing sperm competition. Front. Genet. 10: 820.
Civetta A. and Reimer A. 2014. Positive selection at a seminal fluid gene within a QTL for conspecific sperm precedence. Genetica, 142(6): 537–543.
Clark N.L., Aagaard J.E., and Swanson W.J. 2006. Evolution of reproductive proteins from animals and plants. Reproduction, 131(1): 11–22.
Coolon J.D., McManus C.J., Stevenson K.R., Graveley B.R., and Wittkopp P.J. 2014. Tempo and mode of regulatory evolution in Drosophila. Genome Res. 24(5): 797–808.
Coolon J.D., Stevenson K.R., Mcmanus C.J., Yang B., Graveley B.R., and Wittkopp P.J. 2015. Molecular mechanisms and evolutionary processes contributing to accelerated divergence of gene expression on the Drosophila X chromosome. Mol. Biol. Evol. 32(10): 2605–2615.
Cooper J.C., Lukacs A., Reich S., Schauer T., Imhof A., Phadnis N., and Larracuente A.M. 2019. Altered localization of hybrid incompatibility proteins in Drosophila. Mol. Biol. Evol. 36(8): 1783–1792.
Coyne J.A. 2018. “Two Rules of Speciation” revisited. Mol. Ecol. 27(19): 3749–3752.
Coyne J.A., Simeonidis S., and Rooney P. 1998. Relative paucity of genes causing inviability in hybrids between Drosophila melanogaster and D. simulans. Genetics, 150(3): 1091–1103.
Dagilis A.J., Kirkpatrick M., and Bolnick D.I. 2019. The evolution of hybrid fitness during speciation. PLoS Genet. 15(5): e1008125.
David J.R., Araripe L.O., Chakir M., Legout H., Lemos B., Pétavy G., et al. 2005. Male sterility at extreme temperatures: a significant but neglected phenomenon for understanding Drosophila climatic adaptations. J. Evol. Biol. 18(4): 838–846.
Durand S., Bouché N., Perez Strand, E., Loudet O., and Camilleri C. 2012. Rapid establishment of genetic incompatibility through natural epigenetic variation. Curr. Biol. 22(4): 326–331.
Ellegren H. and Parsch J. 2007. The evolution of sex-biased genes and sex-biased gene expression. Nat. Rev. Genet. 8(9): 689–698.
Fedorka K.M., Winterhalter W.E., and Ware B. 2011. Perceived sperm competition intensity influences seminal fluid protein production prior to courtship and mating. Evolution, 65(2): 584–590.
Ferguson J., Gomes S., and Civetta A. 2013. Rapid male-specific regulatory divergence and down regulation of spermatogenesis genes in Drosophila species hybrids. PLoS ONE, 8(4): e61575.
Findlay G.D., Yi X., MacCoss M.J., and Swanson W.J. 2008. Proteomics reveals novel Drosophila seminal fluid proteins transferred at mating. PLoS Biol. 6(7): e178.
Fuyama Y. 1983. Species-specificity of paragonial substances as an isolating mechanism in Drosophila. Experientia, 39(2): 190–192.
Garbaczewska M., Billeter J.C., and Levine J.D. 2013. Drosophila melanogaster males increase the number of sperm in their ejaculate when perceiving rival males. J. Insect Physiol. 59(3): 306–310.
Gavrilets S. 2014. Is sexual conflict an “Engine of speciation”? Cold Spring Harb. Perspect. Biol. 6(12): a017723.
Go A., Alhazmi D., and Civetta A. 2019. Altered expression of cell adhesion genes and hybrid male sterility between subspecies of Drosophila pseudoobscura. Genome, 62(10): 657–663.
Gomes S. and Civetta A. 2014. Misregulation of spermatogenesis genes in Drosophila hybrids is lineage-specific and driven by the combined effects of sterility and fast male regulatory divergence. J. Evol. Biol. 27(9): 1775–1783.
Gomes S. and Civetta A. 2015. Hybrid male sterility and genome-wide misexpression of male reproductive proteases. Sci. Rep. 5: 11976.
Grath S., Baines J.F., and Parsch J. 2009. Molecular evolution of sex-biased genes in the Drosophila ananassae subgroup. BMC Evol. Biol. 9(1): 291.
Graze R.M., McIntyre L.M., Main B.J., Wayne M.L., and Nuzhdin S.V. 2009. Regulatory divergence in Drosophila melanogaster and D. simulans, a genomewide analysis of allele-specific expression. Genetics, 183(2): 547–561.
Haerty W., Jagadeeshan S., Kulathinal R.J., Wong A., Ram K.R., Sirot L.K., et al. 2007. Evolution in the fast lane: rapidly evolving sex-related genes in Drosophila. Genetics, 177(3): 1321–1335.
Haldane J.B.S. 1922. Sex ratio and unisexual sterility in hybrid animals. J. Genet. 12(2): 101–109.
Halligan D.L. and Keightley P.D. 2006. Ubiquitous selective constraints in the Drosophila genome revealed by a genome-wide interspecies comparison. Genome Res. 16(7): 875–884.
Hodgins-Davis A., Rice D.P., and Townsend J.P. 2015. Gene expression evolves under a house-of-cards model of stabilizing selection. Mol. Biol. Evol. 32(8): 2130–2140.
Hutter P. and Ashburner M. 1987. Genetic rescue of inviable hybrids between Drosophila melanogaster and its sibling species. Nature, 327(6120): 331–333.
Hutter S., Saminadin-Peter S.S., Stephan W., and Parsch J. 2008. Gene expression variation in African and European populations of Drosophila melanogaster. Genome Biol. 9(1): R12.
Inoue Y. and Watanabe T.K. 1979. Inversion polymorphisms in japanese natural populations of Drosophila melanogaster. Jpn. J. Genet. 54(2): 69–82.
Jagadeeshan S. and Singh R.S. 2005. Rapidly evolving genes of Drosophila: Differing levels of selective pressure in testis, ovary, and head tissues between sibling species. Mol. Biol. Evol. 22(9): 1793–1801.
Jiang Z.F. and Machado C.A. 2009. Evolution of sex-dependent gene expression in three recently diverged species of Drosophila. Genetics, 183(3): 1175–1185.
Johnson, N.A. 2000. Gene interactions and the origin of species. In Epistasis and the Evolutionary Process. Edited by J. Wolf, E. Brodie, and M. Wade. Oxford University Publishes, New York. pp. 197–212.
Kemkemer C., Catalán A., and Parsch J. 2014. “Escaping” the X chromosome leads to increased gene expression in the male germline of Drosophila melanogaster. Heredity, 112(2): 149–155.
Kern A.D., Jones C.D., and Begun D.J. 2004. Molecular population genetics of male accessory gland proteins in the Drosophila simulans complex. Genetics, 167(2): 725–735.
Khaitovich P., Hellmann I., Enard W., Nowick K., Leinweber M., Franz H., et al. 2005. Evolution: Parallel patterns of evolution in the genomes and transcriptomes of humans and chimpanzees. Science, 309(5742): 1850–1854.
King M.C. and Wilson A.C. 1975. Evolution at two levels in humans and chimpanzees. Science, 188(4184): 107–116.
Kohn M.H., Shapiro J., and Wu C.I. 2008. Decoupled differentiation of gene expression and coding sequence among Drosophila populations. Genes Genet. Syst. 83(3): 265–273.
Kraaijeveld K., Kraaijeveld-Smit F.J.L., and Maan M.E. 2011. Sexual selection and speciation: the comparative evidence revisited. Biol. Rev. 86(2): 367–377.
Lafon-Placette C. and Köhler C. 2015. Epigenetic mechanisms of postzygotic reproductive isolation in plants. Curr. Opin. Plant Biol. 23: 39–44.
Landry C.R., Wittkopp P.J., Taubes C.H., Ranz J.M., Clark A.G., and Hartl D.L. 2005. Compensatory cis-trans evolution and the dysregulation of gene expression in interspecific hybrids of Drosophila. Genetics, 171(4): 1813–1822.
Lemos B., Bettencourt B.R., Meiklejohn C.D., and Hartl D.L. 2005. Evolution of proteins and gene expression levels are coupled in Drosophila and are independently associated with mRNA abundance, protein length, and number of protein–protein interactions. Mol. Biol. Evol. 22(5): 1345–1354.
Lemos B., Araripe L.O., and Hartl D.L. 2008. Polymorphic Y chromosomes harbor cryptic variation with manifold functional consequences. Science, 319(5859): 91–93.
Lemos B., Branco A.T., and Hartl D.L. 2010. Epigenetic effects of polymorphic Y chromosomes modulate chromatin components, immune response, and sexual conflict. Proc. Natl. Acad. Sci. U.S.A. 107(36): 15826–15831.
Li V.C., Davis J.C., Lenkov K., Bolival B., Fuller M.T., and Petrov D.A. 2009. Molecular evolution of the testis TAFs of Drosophila. Mol. Biol. Evol. 26(5): 1103–1116.
Llopart A. 2012. The rapid evolution of X-linked male-biased gene expression and the large-X effect in Drosophila yakuba, D. santomea, and their hybrids. Mol. Biol. Evol. 29(12): 3873–3886.
Llopart A., Brud E., Pettie N., and Comeron J.M. 2018. Support for the dominance theory in Drosophila transcriptomes. Genetics, 210(2): 703–718.
Mack K.L. and Nachman M.W. 2017. Gene regulation and speciation. Trends Genet. 33(1): 68–80.
Maside X.R., Barral J.P., and Naveira H.F. 1998. Hidden effects of X chromosome introgressions on spermatogenesis in Drosophila simulans × D. mauritiana hybrids unveiled by interactions among minor genetic factors. Genetics, 150(2): 745–754.
McManus C.J., Coolon J.D., Duff M.O., Eipper-Mains J., Graveley B.R., and Wittkopp P.J. 2010. Regulatory divergence in Drosophila revealed by mRNA-seq. Genome Res. 20(6): 816–825.
Meiklejohn C.D., Parsch J., Ranz J.M., and Hartl D.L. 2003. Rapid evolution of male-biased gene expression in Drosophila. Proc. Natl. Acad. Sci. U.S.A. 100(17): 9894–9899.
Meiklejohn C.D., Landeen E.L., Cook J.M., Kingan S.B., and Presgraves D.C. 2011. Sex chromosome-specific regulation in the Drosophila male germline but little evidence for chromosomal dosage compensation or meiotic inactivation. PLoS Biol. 9(8): e1001126.
Meisel R.P., Han M.V., and Hahn M.W. 2009. A complex suite of forces drives gene traffic from Drosophila X chromosomes. Genome Biol. Evol. 1: 176–188.
Michalak P. and Ma D. 2008. The acylphosphatase (Acyp) alleles associate with male hybrid sterility in Drosophila. Gene, 416(1–2): 61–65.
Michalak P. and Noor M.A.F. 2003. Genome-wide patterns of expression in Drosophila pure species and hybrid males. Mol. Biol. Evol. 20(7): 1070–1076.
Miller C.J.J. and Matute D.R. 2017. The effect of temperature on Drosophila hybrid fitness. Genes Genomes Genet. 7(2): 377–385.
Moehring A.J., Teeter K.C., and Noor M.A.F. 2007. Genome-wide patterns of expression in Drosophila pure species and hybrid males. II. Examination of multiple-species hybridizations, platforms, and life cycle stages. Mol. Biol. Evol. 24(1): 137–145.
Mohorianu I., Bretman A., Smith D.T., Fowler E.K., Dalmay T., and Chapman T. 2017. Genomic responses to the socio-sexual environment in male Drosophila melanogaster exposed to conspecific rivals. RNA, 23(7): 1048–1059.
Nourmohammad A., Rambeau J., Held T., Kovacova V., Berg J., and Lässig M. 2017. Adaptive evolution of gene expression in Drosophila. Cell Rep. 20(6): 1385–1395.
Nuzhdin S.V., Wayne M.L., Harmon K.L., and McIntyre L.M. 2004. Common pattern of evolution of gene expression level and protein sequence in Drosophila. Mol. Biol. Evol. 21(7): 1308–1317.
Orr H.A. 1996. Dobzhansky, Bateson, and the genetics of speciation. Genetics, 144(4): 1331–1335.
Orr H.A. and Irving S. 2001. Complex epistasis and the genetic basis of hybrid sterility in the Drosophila pseudoobscura Bogota-U.S.A. hybridization. Genetics, 158(3): 1089–1100.
Osada N., Miyagi R., and Takahashi A. 2017. Cis- and trans-regulatory effects on gene expression in a natural population of Drosophila melanogaster. Genetics, 206(4): 2139–2148.
Parisi M., Nuttall R., Naiman D., Bouffard G., Malley J., Andrews J., et al. 2003. Paucity of genes on the Drosophila X chromosome showing male-biased expression. Science, 299(5607): 697–700.
Parsch J. and Ellegren H. 2013. The evolutionary causes and consequences of sex-biased gene expression. Nat. Rev. Genet. 14(2): 83–87.
Patlar B. and Ramm S.A. 2020. Genotype-by-environment interactions for seminal fluid expression and sperm competitive ability. J. Evol. Biol. 33(2): 225–236.
Patlar B., Weber M., and Ramm S.A. 2019. Genetic and environmental variation in transcriptional expression of seminal fluid proteins. Heredity, 122(5): 595–611.
Pavey S.A., Collin H., Nosil P., and Rogers S.M. 2010. The role of gene expression in ecological speciation. Ann. N.Y. Acad. Sci. 1206: 110–129.
Perez D.E. and Wu C.I. 1995. Further characterization of the Odysseus locus of hybrid sterility in Drosophila: Oone gene is not enough. Genetics, 140(1): 201–206.
Pfennig D.W., Wund M.A., Snell-Rood E.C., Cruickshank T., Schlichting C.D., and Moczek A.P. 2010. Phenotypic plasticity’s impacts on diversification and speciation. Trends Ecol. Evol. 25(8): 459–467.
Phadnis N. 2011. Genetic architecture of male sterility and segregation distortion in Drosophila pseudoobscura Bogota-U.S.A. hybrids. Genetics, 189(3): 1001–1009.
Phadnis N. and Orr H.A. 2009. A single gene causes both male sterility and segregation distortion in Drosophila hybrids. Science, 323(5912): 376–379.
Phadnis N., Baker E.P., Cooper J.C., Frizzell K.A., Hsieh E., de La Cruz A.F.A., et al. 2015. An essential cell cycle regulation gene causes hybrid inviability in Drosophila. Science, 350(6267): 1552–1555.
Pontecorvo G. 1943. Viability interactions between chromosomes of Drosophila melanogaster and Drosophila simulans. J. Genet. 45(1): 51–66.
Presgraves D.C. 2008. Sex chromosomes and speciation in Drosophila. Trends Genet. 24(7): 336–343.
Price C.S.C., Kim C.H., Posluszny J., and Coyne J.A. 2000. Mechanisms of conspecific sperm precedence in Drosophila. Evolution, 54(6): 2028–2037.
Ranz J.M., Castillo-Davis C.I., Meiklejohn C.D., and Hartl D.L. 2003a. Sex-dependent gene expression and evolution of the Drosophila transcriptome. Science, 300(5626): 1742–1745.
Ranz J.M., Ponce A.R., Hartl D.L., and Nurminsky D. 2003b. Origin and evolution of a new gene expressed in the Drosophila sperm axoneme. Genetica, 118(2–3): 233–244.
Rifkin S.A., Kim J., and White K.P. 2003. Evolution of gene expression in the Drosophila melanogaster subgroup. Nat. Genet. 33(2): 138–144.
Ritchie M.G. 2007. Sexual selection and speciation. Annu. Rev. Ecol. Evol. Syst. 38(1): 79–102.
Rohmer C., David J.R., Moreteau B., and Joly D. 2004. Heat induced male sterility in Drosophila melanogaster: Adaptive genetic variations among geographic populations and role of the Y chromosome. J. Exp. Biol. 207(Pt. 16): 2735–2743.
Sawamura K., Roote J., Wu C.I., and Yamamoto M.T. 2004. Genetic complexity underlying hybrid male sterility in Drosophila. Genetics, 166(2): 789–796.
Servedio M.R. and Bürger R. 2014. The counterintuitive role of sexual selection in species maintenance and speciation. Proc. Natl. Acad. Sci. U.S.A. 111(22): 8113–8118.
Signor S.A. and Nuzhdin S.V. 2018. The evolution of gene expression in cis and trans. Trends Genet. 34(7): 532–544.
Singh, R.S. 1990. Patterns of species divergence and genetic theories of speciation. In Population biology. Edited by K. Wohrmann and S.K. Jain. Springer-Verlag Press, Berlin. pp. 231–265.
Singh, R.S. 1999. Toward a unified theory of speciation. In Evolutionary genetics: From molecules to morphology. Edited by R.S. Singh and C. Krimbas. Cambridge University Press, New York. pp. 573–608.
Sirot L.K., Findlay G.D., Sitnik J.L., Frasheri D., Avila F.W., and Wolfner M.F. 2014. Molecular characterization and evolution of a gene family encoding both female- and male-specific reproductive proteins in Drosophila. Mol. Biol. Evol. 31(6): 1554–1567.
Sun S., Ting C.T., and Wu C.I. 2004. The normal function of a speciation gene, Odysseus, and its hybrid sterility effect. Science, 305(5680): 81–83.
Swanson W.J. and Vacquier V.D. 2002. The rapid evolution of reproductive proteins. Nat. Rev. Genet. 3: 137–144.
Swanson W.J., Clark A.G., Waldrip-Dail H.M., Wolfner M.F., and Aquadro C.F. 2001. Evolutionary EST analysis identifies rapidly evolving male reproductive proteins in Drosophila. Proc. Natl. Acad. Sci. U.S.A. 98(13): 7375–7379.
Sweigart A.L. 2010. Simple Y-autosomal incompatibilities cause hybrid male sterility in reciprocal crosses between Drosophila virilis and D. americana. Genetics, 184(3): 779–787.
Takahasi K.R., Matsuo T., and Takano-Shimizu-Kouno T. 2011. Two types of cis-trans compensation in the evolution of transcriptional regulation. Proc. Natl. Acad. Sci. U.S.A. 108(37): 15276–15281.
Tang S. and Presgraves D.C. 2009. Evolution of the Drosophila nuclear pore complex results in multiple hybrid incompatibilities. Science, 323(5915): 779–782.
Tao Y., Zeng Z.B., Li J., Hartl D.L., and Laurie C.C. 2003. Genetic dissection of hybrid incompatibilities between Drosophila simulans and D. mauritiana. II. Mapping hybrid male sterility loci on the third chromosome. Genetics, 164(4): 1399–1418.
Ting C.T., Tsaur S.C., Wu M.L., and Wu C.I. 1998. A rapidly evolving homeobox at the site of a hybrid sterility gene. Science, 282(5393): 1501–1504.
Ting C.T., Tsaur S.C., Sun S., Browne W.E., Chen Y.C., Patel N.H., and Wu C.I. 2004. Gene duplication and speciation in Drosophila: evidence from the Odysseus locus. Proc. Natl. Acad. Sci. U.S.A. 101(33): 12232–12235.
Voordeckers K., Pougach K., and Verstrepen K.J. 2015. How do regulatory networks evolve and expand throughout evolution? Curr. Opin. Biotechnol. 34: 180–188.
Wang P.J., McCarrey J.R., Yang F., and Page D.C. 2001. An abundance of X-linked genes expressed in spermatogonia. Nat. Genet. 27(4): 422–426.
Wigby S., Perry J.C., Kim Y.H., and Sirot L.K. 2016. Developmental environment mediates male seminal protein investment in Drosophila melanogaster. Funct. Ecol. 30(3): 410–419.
Wittkopp P.J., Haerum B.K., and Clark A.G. 2008. Regulatory changes underlying expression differences within and between Drosophila species. Nat. Genet. 40(3): 346–350.
Wong A., Turchin M.C., Wolfner M.F., and Aquadro C.F. 2008. Evidence for positive selection on Drosophila melanogaster seminal fluid protease homologs. Mol. Biol. Evol. 25(3): 497–506.
Wu C. and Davis A. 1993. Evolution of postmating reproductive isolation: the composite nature of Haldane’s Rule and its genetic bases. Am. Nat. 142(2): 187–212.
Wyman M.J., Cutter A.D., and Rowe L. 2012. Gene duplication in the evolution of sexual dimorphism. Evolution, 66(5): 1556–1566.
Yanicostas C., Ferrer P., Vincent A., and Lepesant J.A. 1995. Separate cis-regulatory sequences control expression of serendipity β and janus A, two immediately adjacent Drosophila genes. Mol. Gen. Genet. 246(5): 549–560.
Zhang Y., Sturgill D., Parisi M., Kumar S., and Oliver B. 2007. Constraint and turnover in sex-biased gene expression in the genus Drosophila. Nature, 450(7167): 233–237.

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cover image Genome
Volume 64Number 2February 2021
Pages: 63 - 73


Received: 27 February 2020
Accepted: 25 July 2020
Published online: 30 July 2020


This article is part of the special issue entitled “CanFly XV 2019”. A collection of invited papers from the Canadian Drosophila Research Conference, Toronto, Ontario, 9–13 June 2019.


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Key Words

  1. gene expression
  2. plasticity
  3. hybrid incompatibility
  4. speciation


  1. expression génique
  2. plasticité
  3. incompatibilité hybride
  4. spéciation



Bahar Patlar
Department of Biology, University of Winnipeg, Winnipeg, MB R3B 2E9, Canada.
Alberto Civetta*
Department of Biology, University of Winnipeg, Winnipeg, MB R3B 2E9, Canada.


Alberto Civetta currently serves as an Associate Editor; peer review and editorial decisions regarding this manuscript were handled by Thomas Merritt.
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1. Divergence of X-linked trans regulatory proteins and the misexpression of gene targets in sterile Drosophila pseudoobscura hybrids
2. Seminal fluid gene expression and reproductive fitness in Drosophila melanogaster
3. Viviparity and habitat restrictions may influence the evolution of male reproductive genes in tsetse fly (Glossina) species

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