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doi: 10.1111/jeb.12345 The role of sex chromosomes in sexual dimorphism: discordance between molecular and phenotypic data R. DEAN & J. E. MANK Department of Genetics, Evolution and Environment, University College London, London, UK Keywords: Abstract feminization; gene expression; masculinization; sex chromosomes; sexual dimorphism; sexual selection. In addition to initial sex determination, genes on the sex chromosomes are theorized to play a particularly important role in phenotypic differences between males and females. Sex chromosomes in many species display molecular signatures consistent with these theoretical predictions, particularly through sex-specific gene expression. However, the phenotypic implications of this molecular signature are unresolved, and the role of the sex chromosomes in quantitative genetic studies of phenotypic sex differences is largely equivocal. In this article, we examine molecular and phenotypic data in the light of theoretical predictions about masculinization and feminization of the sex chromosomes. Additionally, we discuss the role of genetic and regulatory complexities in the genome–phenotype relationship, and ultimately how these affect the overall role of the sex chromosomes in sex differences. Are sex chromosomes important in sexual dimorphism? In addition to the differences associated with sex determination, development of the gonad and gamete delivery, males and females in many organisms exhibit an array of somatic dimorphisms, including morphology, anatomy, life history and behaviour, among many others (Fairbairn, 2013). Sexually dimorphic phenotypes often have complex genetic architectures and questions related to how separate female and male phenotypes are encoded within a genome that is largely shared have long been at the heart of evolutionary biology (Lande, 1980, 1987; Reeve & Fairbairn, 2001; Badyaev, 2002). The shared genome places a constraint on the evolution of male- and female-specific phenotypes (e.g. Delph et al., 2004; Poissant et al., 2010), and this means that differences between male- and female-specific fitness optima can lead to sexual conflict. Concerns about this constraint have led many to look to the sex chromosomes, the only regions of the genome that Correspondence: Judith E. Mank, Department of Genetics, Evolution and Environment, University College London, The Darwin Building, Gower Street, London WC1E 6BT, UK. Tel.: +44 (203) 108 4228; e-mail: [email protected] differ between the sexes, as potential hot spots for the genes underlying sexual dimorphism and potential foci of sexual conflict. Theoretical models have long predicted that the sex chromosomes should play a disproportionately large role in sexual antagonism (e.g. Rice, 1984; but see Fry, 2010). This theory can be extended to sexual dimorphism if the resolution of sexual antagonism via modifiers of sexually antagonistic loci is also X-linked (Rice, 1984). However, the predictions of this latter two locus model, requiring both a sex-linked sexually antagonist coding locus and a sex-linked sex-specific regulatory element, have been questioned (Connallon & Clark, 2010). Regardless of this debate, there is an expansive and compelling body of evolutionary theory about the role of the sex chromosomes in sexual conflict and for different models of sexual selection (Rice, 1984; Kirkpatrick & Hall, 2004; Albert & Otto, 2005; Van Doorn & Kirkpatrick, 2007, among many others). There are two primary types of sex chromosome systems, male (XX XY) and female (ZW ZZ) heterogamety, which between them have four types (X,Y,Z and W) of sex chromosomes. In male heterogametic systems, females have two X chromosomes and males one X chromosome and one Y chromosome. In female heterogamety, females have one Z chromosome and one W chromosome, and males two Z chromosomes. There- ª 2014 THE AUTHORS. J. EVOL. BIOL. 27 (2014) 1443–1453 JOURNAL OF EVOLUTIONARY BIOLOGY ª 2014 EUROPEAN SOCIETY FOR EVOLUTIONARY BIOLOGY 1443 1444 R. DEAN AND J. E. MANK fore, Y and W chromosomes are limited to males and females, respectively, whereas X and Z chromosomes are shared by both sexes but are more often present in females (X chromosome) or males (Z chromosome). In theory, both coding and regulatory loci on each of the sex chromosome types should be sexualized in unique and specific ways (Table 1). Even though the sex-limited Y and W chromosomes often contain relatively few genes, those that remain are thought to play a crucial role in male (for the Y chromosome) and female (for the W chromosome) traits, as strong sex-specific selection is needed to maintain genes on these chromosomes once recombination is suppressed (Bachtrog, 2013). X and Z chromosomes are thought to be masculinized (having accumulated a greater degree of male-benefit alleles than the autosomes) and feminized (accumulating greater female-benefit alleles than the autosomes) in different ways depending on the dominance of alleles. In male heterogamety, the hemizygosity experienced by males may give the X chromosome a disproportionately large role in traits encoded by recessive alleles that benefit males, as X-linked genes are always exposed to selection in males. Additionally, sexual selection models Table 1 Predicted sexualization of sex chromosomes. Sex Chromosome Type Sex-specific effects Male heterogamety X chromosome Dominant Accumulation of femalebenefit alleles and/or female-biased genes (feminization) Fewer than expected male-benefit alleles and/or male-biased genes (demasculinization) Y chromosome Accumulation of malebenefit alleles, only expressed in males (masculinization) Female heterogamety Z chromosome Dominant Accumulation of malebenefit alleles and/or male-biased genes (masculinization) Fewer than expected female-benefit alleles and/or female-biased genes (defeminization) W chromosome Accumulation of femalebenefit alleles, only expressed in females (feminization) Recessive Accumulation of malebenefit alleles and/or male-biased genes (masculinization) Fewer than expected female-benefit alleles and/or female-biased genes (defeminization) Recessive Accumulation of femalebenefit alleles and/or female-biased genes (feminization) Fewer than expected male-benefit alleles and/or male-biased genes (demasculinization) suggest that X chromosomes should accumulate genes that act as honest signals of male quality (Kirkpatrick & Hall, 2004). Alternatively, the fact that the X chromosome is more often present in females may give it a larger role in traits encoded by dominant alleles that benefit females because the X chromosome is twice as often present in females than males (Rice, 1984). These predictions in converse are expected of Z chromosomes (i.e. a feminization for Z-linked recessive variation, and masculinization of dominant alleles). Additionally, the inheritance pattern of Z chromosomes, which are the only sex chromosome that can be passed from a male to both his sons and his daughters, is thought to foster the spread of sexually selected traits that are the product of female preference (Reeve & Pfennig, 2003; Kirkpatrick & Hall, 2004). And these are just some of the models suggesting that sex chromosomes are likely to play a large role in sexually dimorphic and sexually selected traits, with many other variations pervading the literature (e.g. Albert & Otto, 2005; Van Doorn & Kirkpatrick, 2007). Predictions and assumptions about the role of the sex chromosomes in sex differences are often so pervasive that it is sometimes assumed that all sex differences ultimately derive from sex-linked genes or have hijacked the sex-determination pathway (Williams & Carroll, 2009; Matson & Zarkower, 2012). The latter view implies that sex determination is always based on sex chromosome complement; however, most animals, many of which have clear sexual dimorphism, lack sex chromosomes. It is therefore clear that sex chromosomes are not required for sexual dimorphism. Consequently, it follows that not all sexually selected or sexually dimorphic traits need necessarily be sex-linked in species with sex chromosomes. Accepting this reality leads to some important questions: How important are the sex chromosomes in phenotypic sex differences? When the sex chromosomes are responsible for phenotypic dimorphisms, what is the underlying genetic mechanism? In species without sex chromosomes, how are sexually dimorphic phenotypes encoded? Testing and quantifying the role of the sex chromosomes in phenotypic sex differences has been a major endeavour in many laboratories for quite some time, and the results have been somewhat mixed. Although some sexually dimorphic phenotypes have been linked to sex chromosomes (Cowley et al., 1986; Chase et al., 2005; Kitano et al., 2009, although see Saetre et al., 2003; Roberts et al., 2009; Natri et al., 2013), many others have not (e.g. Knief et al., 2012; Poissant et al., 2012; Schielzeth et al., 2012). Anecdotal, species-specific reports are heavily influenced by a reporting bias, and few meta-analyses recover a disproportionately large role for the sex chromosomes in sexually dimorphic phenotypes or sex-specific fitness. For example, a survey of putatively sexually selected genes in Drosophila melanogaster (Fitzpatrick, 2004) did not detect ª 2014 THE AUTHORS. J. EVOL. BIOL. 27 (2014) 1443–1453 JOURNAL OF EVOLUTIONARY BIOLOGY ª 2014 EUROPEAN SOCIETY FOR EVOLUTIONARY BIOLOGY Sex chromosomes and sexual dimorphism significant over-representation of sex linkage. Additionally, a meta-analysis of genetic variance in several sexually dimorphic traits in birds did not detect significantly more sex linkage than the size of the sex chromosome would predict (Husby et al. 2013). Similarly, there was no significant association between sex chromosome type and sexually selected traits in fish (Mank et al., 2006). More recently, molecular work has used gene expression and other regulatory differences between females and males to test theoretical predictions about sexualization of the sex chromosomes. Under the assumption that male-biased genes are beneficial to males and female-biased genes are beneficial to females (e.g. Connallon & Clark, 2011; Pointer et al., 2013; Table 1), gene expression data can be used to test for significant masculinization (more male-biased genes than expected) or feminization (more female-biased genes than expected) of sex chromosome gene expression. Molecular data interpreted within this framework are far more concordant than phenotypic studies, with a consistent pattern of masculinization and/or feminization of X, Y, Z and W chromosomes across different species and in accordance with theoretical predictions. The pattern is often so clear that it is difficult at times to understand why sex chromosomes are not always the major players in phenotypic studies of sexual dimorphism. Our goal here is to address the discordance between phenotypic and molecular studies. To do this, we attempt to synthesize phenotypic and molecular studies related to the sexualization of the sex chromosomes. We examine the theory and empirical data on this topic and speculate wildly as to why molecular genetic and phenotypic data might not show concordant patterns. The role of the sex chromosomes in phenotypic sexual dimorphism and sexspecific fitness There are empirical data to support an important role for the sex-limited chromosomes, the male-limited Y chromosome in XX-XY species and the female-limited W in ZZ-ZW species, in sex-specific traits. For example, many male colour polymorphisms have been mapped to the guppy Y chromosome (Winge, 1922), the Y chromosome is important for male fitness in Drosophila (Chippindale & Rice, 2001; Lemos et al., 2008), the human Y chromosome is crucial to male fertility (Lange et al., 2009), and the Y chromosome in Silene latifolia has been shown to control many dimorphic floral traits (Scotti & Delph, 2006; Delph et al., 2010). Similarly, W chromosomes have been shown to harbour female coloration genes in cichlids (Roberts et al. 2009; Parnell & Streelman, 2013) and play a key role in female fertility in chickens (Moghadam et al., 2012). There are also examples of the homogametic sex chromosomes, the X and the Z, playing important roles 1445 in sex-specific phenotypes. For example, the X chromosome influences sexually antagonistic fitness variation (Gibson et al., 2002; Foerster et al., 2007; Innocenti & Morrow, 2010), sexually selected behavioural and morphological traits (Reinhold, 1998), sexual dimorphism in stalked-eyed fly eye span (Wolfenbarger & Wilkinson, 2001), dimorphism in body size in dogs (Chase et al., 2005), dimorphic expression of Drosophila cuticular hydrocarbons (Chenoweth & Blows, 2003; Chenoweth et al., 2008) and a suite of dimorphic Drosophila morphometrics (Cowley et al., 1986; Cowley & Atchley, 1988). Similarly, in female heterogametic systems, female mating preference genes in a moth were identified on the Z chromosome (Iyengar et al., 2002), and female mate preference and male plumage traits have been linked to the flycatcher Z chromosome (Saetre et al., 2003; Saether et al., 2007). The examples above do not represent an exhaustive list, but they do illustrate the power of species-specific reports on particular phenotypes. Reading through these examples, it may seem as although the sex chromosomes play a huge role in sexual dimorphism. However, there are three things to consider: First, some of the above cases do not make clear how often sexually dimorphic traits have been shown to be under autosomal control, for instance dimorphism over beak coloration and size in finches (Knief et al., 2012; Schielzeth et al., 2012), male dimorphism in turkeys (Pointer et al., 2013), horn traits in big horn sheep (Poissant et al., 2012) and, for sex-specific phenotypes, mate preferences in Heliconius butterflies (Merrill et al., 2011). Meta-analyses synthesizing multiple studies, species or traits can create a less-biased estimate of the role of sex linkage in sexual dimorphism. Although they are of course dependent upon the underlying literature and can be influenced by reporting and publication biases, they are still in many ways fairer and less likely to be influenced by reporting and journal preferences. Some meta-analyses do report a disproportionately large role of the sex chromosomes (e.g. Reinhold, 1998; Lindholm & Breden, 2002); however, more often they do not recover a larger role than would be expected based on the relative size of the sex chromosomes in sex-specific traits (Fitzpatrick, 2004; Fairbairn & Roff, 2006; Mank et al., 2006; Husby et al., 2013). Second, there is a strong reporting bias. Because of the clear theoretical expectations, researchers recovering sex linkage for sexually dimorphic traits often emphasize the role of sex chromosomes in the given trait in the resulting manuscript. Those studies that fail to recover the predicted relationship are less likely to discuss the predictions or lack of observed sex linkage. And, because of the theoretical expectations, studies that do recover sex linkage may be more likely to be published in higher impact multidisciplinary journals, whereas those that do not, often receive less notice. ª 2014 THE AUTHORS. J. EVOL. BIOL. 27 (2014) 1443–1453 JOURNAL OF EVOLUTIONARY BIOLOGY ª 2014 EUROPEAN SOCIETY FOR EVOLUTIONARY BIOLOGY 1446 R. DEAN AND J. E. MANK Third, for polygenic traits spanning multiple loci, it is important to consider the relative size of the sex chromosomes compared with the autosomal portion of the genome when determining whether they play a disproportionately large role. For example, the Drosophila melanogaster X chromosome constitutes around 20% of the genome and carries >15% of the coding genes. Given this large size, many traits, sexually dimorphic or not, will map to the sex chromosomes, and it is important to account for the relative size of the sex chromosomes in such studies. An over-representation can only be assessed with an appropriate null expectation. For example, Wolfenbarger and Wilkinson (2001) showed that the X chromosome in stalk-eyed flies accounted for 25% variation in eye span, even though the chromosome harbours 12% of the male genome. This suggests that the X is over-represented in this sexually selected trait. However, there are other considerations, such as dosage compensation (below) that should be considered. Molecular signatures of sex chromosome sexualization The theoretical models that predict that the sex chromosomes should accumulate genes with sex-specific fitness effects, and by extension genes underlying sexual dimorphism (e.g. Rice, 1984), have recently been extended to molecular data under two assumptions: first, sex-biased genes represent genes with different expression optima for females and males (Connallon & Clark, 2011; Pointer et al., 2013), and second, sexbiased genes represent at least partially resolved sexual conflict (Connallon & Knowles, 2005; Connallon & Clark, 2010). In this framework, genes expressed at higher levels in females (female-biased genes) confer female benefits and contribute to female-specific phenotypes, and genes expressed at higher levels in males (male-biased genes) confer benefits to males and encode male-specific phenotypes. Regions of the genome, particularly the sex chromosomes, have been shown to be sexualized in specific ways. Regions that contain more female-biased or male-biased genes than would be expected due to chance are often referred to as feminized or masculinized, respectively. Similarly, regions can also be defeminized, with a deficit of female-biased genes or demasculinized with a deficit of male-biased genes. The models are really not applicable to the sex-limited nonrecombining regions of Y and W chromosomes, which by definition can only be expressed in males and females, respectively. The theory predicts an expected feminization of X chromosomes for dominant alleles, which would be observable at the molecular level through an excess of female-biased genes, possibly concurrent with demasculinization, or a deficit of male-biased genes, when compared to the autosomes. Similarly, we would expect, based on theoretical predictions, a masculiniza- tion of Z chromosomes through an excess of malebiased dominant alleles, possibly in concert with a decrease in female-biased genes (defeminization). Hemizygosity would lead to a masculinization of X chromosomes for recessive alleles and feminization of Z chromosomes. Sexualization of X and Z chromosomes has been documented in nearly every species thus far assessed (Table 2). For example, the X chromosome has been both feminized (it has an over-abundance of femalebiased genes) and demasculinized (it is depauperate in male-biased loci) in Drosophila (Parisi et al., 2003; Ranz et al. 2003; Sturgill et al., 2007; Meisel et al., 2012). The mammalian X chromosome also shows evidence of feminization (Khil et al., 2004), although young malebiased genes are enriched on the mammalian X (Zhang et al., 2010). Additionally, both the X chromosomes of C. elegans (Reinke et al., 2004) and the flour beetle (Prince et al., 2010) are also feminized, although the latter effect may be due, at least in part, to the peculiar pattern of dosage compensation in this species. The avian Z chromosome is masculinized (Wright et al., 2012) and defeminized (Mank & Ellegren, 2009). The Z chromosome in silk worm also shows patterns of masculinization (Arunkumar et al., 2009), as does the pea aphid X chromosome, potentially due to its unusual transmission pattern resulting from periodic parthenogenesis (Jaquiery et al., 2013). Finally, the mosquito X chromosome shows evidence of demasculinization (Magnusson et al., 2012). However, it is important to note that there are several complicating factors when assessing the relative proportion of sex-biased genes on the sex chromosomes. First, different animals have different mechanisms, with different efficacies, of dosage compensation on the X or Z chromosome (Mank, 2013). The heterogametic sex has only one copy of X- or Z-linked genes compared with the homogametic sex. Because gene dose often correlates with expression level, this means that many genes are expressed less in the heterogametic sex due to halved copy number (Guo et al., 1996; Malone et al., 2012). In some organisms, sex chromosome dosage compensation has evolved to correct for this imbalance. In other organisms, only a small subset of genes are compensated, and the majority of the chromosome shows expression differences between the sexes (reviewed in Mank, 2013). In male heterogametic species with incomplete dosage compensation, the X chromosome will appear to be very strongly femalebiased. Similarly, incomplete dosage compensation in female heterogametic species would appear to lead to the appearance of a very strong masculinization of gene expression. When incomplete dosage compensation is not recognized and corrected for, it can lead to a false perception of an excess of sex-biased genes on sex chromosomes as a function of sexual conflict, rather than dose effects. ª 2014 THE AUTHORS. J. EVOL. BIOL. 27 (2014) 1443–1453 JOURNAL OF EVOLUTIONARY BIOLOGY ª 2014 EUROPEAN SOCIETY FOR EVOLUTIONARY BIOLOGY Sex chromosomes and sexual dimorphism 1447 Table 2 Empirical sexualization of gene expression on the sex chromosomes of various animals. Masculinization Feminization Demasculinization X chromosome Mammals, for young male-biased genes (Zhang et al., 2010) Pea aphid (Jaquiery et al., 2013) Flour beetle (Prince et al., 2010) C. elegans (Magnusson et al., 2012) Fruit fly (Meisel et al., 2012) Mouse (Khil et al., 2004) Mosquito (Magnusson et al., 2012) Fruit fly (Parisi et al., 2003; Sturgill et al., 2007; Bachtrog et al., 2010) Z chromosome Chicken (Wright et al., 2012) Silk worm (Arunkumar et al., 2009) Second, some animals exhibit meiotic sex chromosome inactivation (MSCI) in the heterogametic sex. Although evidence is conflicting, it is thought that MSCI occurs in placental mammals (Turner et al., 2005; Cocquet et al., 2009), where transcription from the X chromosome is nearly entirely shut off in the meiotic cells of males, but might be absent in Drosophila (Meiklejohn et al., 2011; but see Hense et al., 2007; Vibranovski et al., 2012) and birds (Guioli et al., 2012; but see Shoenmakers et al., 2009). In those species where it does occur, if uncorrected for in gonad tissue, MSCI can create a false pattern of female bias on X chromosomes. Even though MSCI has not yet been definitely shown for a Z chromosome and may not occur in any female heterogametic species, it would theoretically exacerbate male-biased expression observed in gonad tissue. Some of the earlier discordant results over relative sexualization of X and Z chromosomes were due to the fact that the presence, absence or efficacy of dosage compensation and MSCI were unknown. However, there are several species where the status of MSCI and dosage compensation is known and accounted for. Even accounting for dosage compensation and MSCI, the X chromosome in both mouse and Drosophila has been feminized for expression (Khil et al., 2004; Meisel et al., 2012, respectively), and the Z chromosome has been masculinized in birds (Wright et al., 2012). The Drosophila X chromosome shows weaker and less consistent evidence of demasculinization (Meisel et al., 2012), although this may be due to the mechanism of dosage compensation in this clade (Vicoso & Charlesworth, 2009), explained in more detail below. Random-X inactivation in female mammals does not in itself present a confounding factor, as it equilibrates gene dose between males and females. However, some genes escape inactivation and are female-biased, which can present a source of bias in the data. Correcting for these species-specific regulatory peculiarities, there is some enrichment of testis-expressed genes on the X (Khil et al., 2004; Meisel et al., 2012). The confounding effects of incomplete dosage compensation in birds make it difficult to assess defeminization, although there is some circumstantial evidence for it (Mank & Ellegren, 2009). Defeminization Chicken (Mank & Ellegren, 2009) Possible causes of discordance The concordance of the molecular sexualization of the sex chromosomes is in stark contrast to the equivocal phenotypic results of the relative role of the sex chromosomes in sexual dimorphism and sex-specific fitness. Gene expression and QTL studies measure different components and require different assumptions, and this, along with several other factors, may explain some of the discordance between these two approaches. Phenotypic studies may underestimate the role of the sex chromosomes QTL studies rely on intrasexual polymorphism and variation, whereas molecular approaches do not. This fact alone may account for a great deal of the discordance. Moreover, molecular studies of gene expression sexualization often ignore any intrasexual variation and simply average over all the individuals of each sex. In addition to being based on different underlying data types, QTL studies can only identify traits for which polymorphisms exist, and this may be particularly problematic for the sex chromosomes, which often have reduced effective population size (Charlesworth et al., 1987). Furthermore, QTL studies sometimes ignore the Y or W chromosome, which of course makes it impossible to determine the role of the sex-limited chromosomes in sexually dimorphic traits. Additionally, quantitative genetic approaches to complex phenotypes, particularly in natural populations with smaller sample numbers, can miscalculate the effect size of specific loci and potentially fail to identify some contributing loci due to the Beavis effect, which leads to a stronger perceived association to fewer QTL in situations with fewer samples (Slate, 2013). For traits with many contributing loci, only a few will be detected, and this could make it difficult to obtain a fair estimate of the contribution of sex-linked genes. Recent work on the transcriptional differences among males with different levels of sexual dimorphism in the wild turkey suggests that some sexspecific traits may have many contributing loci (Pointer et al., 2013). A recent genome-wide association study (GWAS) of sexually dimorphic traits in 270 000 humans also revealed a complex genetic architecture ª 2014 THE AUTHORS. J. EVOL. BIOL. 27 (2014) 1443–1453 JOURNAL OF EVOLUTIONARY BIOLOGY ª 2014 EUROPEAN SOCIETY FOR EVOLUTIONARY BIOLOGY 1448 R. DEAN AND J. E. MANK with many contributing loci (Randall et al., 2013). If this is generally true, then this may limit the ability of QTL approaches, particularly in natural populations, to accurately reconstruct the genetic architecture and therefore the supporting role of the sex chromosomes. Phenotypic studies may underestimate the role of the sex chromosomes through the type of phenotype studied. First, predictions for sex chromosome linkage are strongest for sex-limited or strongly sexually dimorphic phenotypes, and weaker for less dimorphic phenotypes (Fairbairn & Roff, 2006). Second, genomic studies find X chromosomes to be feminized through the accumulation of female-biased genes, and yet most examples of phenotypic sexual dimorphism are sexual display traits which are usually exaggerated in males (Andersson, 1994). Although theory predicts male-biased recessive alleles to accumulate on the X (Rice, 1984), based on the molecular signature of feminization, we might expect X chromosome linkage at the phenotypic level for sexually dimorphic traits that are exaggerated in females. The strongest, and therefore possibly easier to detect, associations between X chromosomes and sexual dimorphism would be expected for highly dimorphic traits exaggerated in females, such as body size in some insects (e.g. Cowley & Atchley, 1988). Additionally, most genes have pleiotropic effects (Wright, 1968) which impose constraints on their evolutionary pathway, and this may complicate the role of the sex chromosomes in sexual dimorphism. A pleiotropic gene subject to sex-specific selection is not free to evolve in response to that selection alone. Its chromosomal location may reflect a mix of sex-specific and nonsex-specific selection (Fitzpatrick, 2004). This mixture may limit the role of the sex chromosomes in sexually dimorphic phenotypes that are controlled by strongly pleiotropic genes, particularly because such genes are not expected on the nonrecombining regions of the sex-limited Y and W chromosomes. Importantly, pleiotropic genes involved in sexually dimorphic traits may contribute to trait variability. However, the degree of pleiotropy differs greatly among loci, and we might expect that the general predictions are fairly accurate for less pleiotropic genes. That said, although the term pleiotropy is usually defined broadly as the multiple functions of a single locus, pleiotropy is actually measured in a variety of different ways. For example, measures of pleiotropy encompass such disparate metrics as tissue-specificity (e.g. expression breadth, Mank et al., 2008; Meisel, 2011), connectivity of genetic networks (Ayroles et al., 2009) or even expression at different life stages (e.g. antagonistic pleiotropy, Williams, 1957). Integrating these various measures into a cohesive test of the role of pleiotropy in sex chromosomes and dimorphism is an important area for future work. In addition to the complications of pleiotropy, regulatory differences further confound our ability to predict and detect the loci underlying sex differences. Most evolutionary theory assumes, usually implicitly, cis-regulation of gene expression, where regulatory elements are relatively close, and definitely on the same chromosome, as the gene they control. Studies across a broad array of species have shown that only a small proportion of all gene regulation is purely in cis, and evidence for an important role of trans-regulation (where more distant elements control expression levels) spans Drosophila (Wayne et al., 2007), C. elegans (Li et al., 2006), humans (Grundberg et al., 2012), mice (Van Nas et al., 2010) and Arabidopsis (West et al., 2007) The location of sexually dimorphic genes and their sex-specific regulation may be disparate, and this complicates matters immensely. More nuanced theoretical predictions with reasonable assumptions about cis- vs. trans-regulation are very much needed. Finally, discordance between molecular and phenotypic findings may simply be a power issue. The restricted ability of genes to move around the genome and the often relatively small size of the sex chromosomes might make detecting patterns of sex chromosome linkage particularly noisy due to stochasticity. The fact that relatively few phenotypic traits have been studied compared with thousands of genes assessed in every transcriptomic analysis might mean we just do not have sufficient power to detect an association. Furthermore, power to detect sex chromosome linkage using the animal model approach is not simply a product of sample size, but also the type of pedigree information (specifically relationships outside the nuclear family) available within the data set (Wolak & Keller, 2014). Even studies with large sample sizes might have deceptively low power when it comes to measuring sex chromosome linkage. Molecular studies may overestimate the sexualization of the sex chromosomes Although there seems to be a clear pattern of sexualization of gene expression on the X and Z chromosomes, it remains unclear how this translates to phenotypic sex differences. The sexualization in many cases only produces relatively small differences in expression between males and females. Do small differences in expression between the sexes translate to observable phenotypic differences? How large does the magnitude of sex bias need to be to have a meaningful phenotypic effect? More work understanding the relationship between sex-biased expression and sexually dimorphic phenotypes is very much needed. Extending studies of sex reversal via sex hormone treatment (such as Gordon et al., 2011) or experimental evolution to increase phenotypic dimorphism (such as Delph et al., 2011) to the transcriptome would be an excellent first start. Additionally, the rate of sexualization of sex chromosome expression seems quite slow (Zhang et al., 2010; Wright et al., 2012), and may be far slower than the ª 2014 THE AUTHORS. J. EVOL. BIOL. 27 (2014) 1443–1453 JOURNAL OF EVOLUTIONARY BIOLOGY ª 2014 EUROPEAN SOCIETY FOR EVOLUTIONARY BIOLOGY Sex chromosomes and sexual dimorphism evolution of the specific sexually dimorphic phenotypes that we are most interested in, which often vary between closely related species. If sexualization of sex chromosomes is slow, how large a role can it play in the evolution of sexually dimorphic phenotypes? Furthermore, what is the degree of sexualization of gene expression for species with minimal levels of sexual dimorphism? It is important to point out that these are related questions and depend on the answers to the questions posed in the preceding paragraph. The confusing role of sex chromosome dosage compensation, or lack thereof Complete sex chromosome dosage compensation may be confined to a small proportion of organisms with sex chromosomes (Mank, 2013), and the presence, absence or efficacy of sex chromosome dosage compensation complicates the role of sex chromosomes in sexual dimorphism considerably. For example, random female X inactivation in mammals (although not strictly a dosage compensation mechanism, sensu Ohno, 1967) invalidates the assumption that the X chromosome is more often selected in females for all types of dominant genes. X inactivation in females is patchy, and tissues are composed of groups of cells with either an active maternal or paternal X chromosome (Carrel & Willard, 2005). For X-linked genes that are not secreted outside the cell wall (cell-autonomous genes), only one copy is expressed within any given patch of cells, and these genes are effectively hemizygous within the cell patch (Haig, 2006). This may suggest that the feminization of the mammalian X chromosome (Khil et al., 2004) applies predominately to secreted genes, which mix throughout the body and remain effectively diploid in females. We do not yet know how this might affect the role of the X in sexually dimorphic phenotypes. Drosophila counters the differences in gene dose of the X chromosome by hyperexpression in males, yet there are limits to how much a gene can be up-regulated. For genes expressed at relatively high levels, males simply cannot hypertranscribe them sufficiently, as the transcriptional machinery becomes saturated. This causes a deficit of highly expressed male-biased genes on the Drosophila X chromosome (Vicoso & Charlesworth, 2009), exactly the type of genes we might expect to be key to male phenotypes. For those species that lack complete sex chromosome dosage compensation, the predicted role of the sex chromosomes in dimorphism is even less clear, and several questions remain unanswered. For example, does the increase in expression of sex-linked genes due to dose effects have a sex-specific phenotypic effect? If so, we might expect the role of the sex chromosomes in sexual dimorphism to be greater in species with incomplete sex chromosome dosage compensation. Also, there is evidence that selection correlates positively with expression 1449 level (Castillo-Davis et al., 2002; Subramanian & Kumar, 2004; Van Dyken & Wade, 2010). If there is a similar relationship between the strength of sex-specific selection and expression level, we might expect X- or Z-linked loci to be under weaker selection in the heterogametic sex in species with incomplete dosage compensation compared with those species where hypertranscription in the heterogametic sex compensates for reduced gene dose. This could lead to the accumulation of alleles benefiting the homogametic sex to be slower in species with complete dosage compensation. Dosage compensation is a largely unexplored issue in regards to the evolution of sexual dimorphism. The recent realization that the efficacy of sex chromosome dosage compensation varies extensively across species may prove important in our ultimate understanding of the role of sex chromosomes in sex differences. Where do we go from here? To better understand this discordance between phenotypic and molecular studies of sex chromosomes and sexual dimorphism, we suggest several future directions that may prove profitable. First, moving towards broadly synthetic meta-analyses of multiple species or multiple traits is a helpful way to present a less-biased view of the role of sex chromosomes vs. autosomes in sexual dimorphism. In particular, studies of this sort should also account for the relative size of the sex chromosomes in their analysis, as we might expect a fair percentage of traits to be linked to the sex chromosomes by chance in species, such as many invertebrates, with relatively large sex chromosomes. As the tide of available phenotypic and genomic data grows, this approach becomes increasingly viable. Another way to bridge the gap in our understanding of the discordance between molecular and phenotypic studies could be to look for the genomic location of regions that regulate sex-biased gene expression (i.e. eQTL approaches). Although eQTL studies may still suffer from some of the same problems as traditional QTL studies, studying a less complex trait (i.e. expression of a specific locus) increases the chances of detecting fewer, but stronger signals. Knowledge of the location of sex-biased genes, their trans-acting regulation and the resulting phenotype would present a fuller picture of the importance of sex chromosomes for sexual dimorphism. Given the growing evidence that complex traits are probably regulated by many loci of small effect (Rockman, 2012), techniques to assess the role of sex chromosomes in shaping phenotypic sexual dimorphism could be at the chromosome level, rather than approaches used to find individual loci. Such approaches that might give useful future advances include chromosome partitioning techniques and whole chromosome substitutions, such as those possible in Drosophila (e.g. Rice et al., 2005). ª 2014 THE AUTHORS. J. EVOL. BIOL. 27 (2014) 1443–1453 JOURNAL OF EVOLUTIONARY BIOLOGY ª 2014 EUROPEAN SOCIETY FOR EVOLUTIONARY BIOLOGY 1450 R. DEAN AND J. E. MANK Many studies of sex-biased expression assume that sex-biased genes are the biochemical basis of sexual dimorphism. Although there is indeed some evidence for this (Connallon & Clark, 2011; Pointer et al., 2013), the relationship between sex-biased genes, sexually dimorphic phenotypes and sex-specific fitness remains rather hazy. We therefore do not really know whether the patterns of masculinization and feminization of gene expression on the sex chromosomes actually have definitive phenotypic implications. Studies with stronger links between phenotype, fitness and gene expression are clearly needed. Finally, the elegant theory that predicts a large role of the sex chromosomes in sexual dimorphism, sexual selection and sexual conflict, such as Rice (1984), Albert & Otto (2005) and Kirkpatrick and Hall (2004), among many others, may not have the necessary genetic complexity. Integrating the role of pleiotropy, cis- vs. trans-regulation and sex chromosome dosage compensation into the mathematics remains to be carried out. Doing so may offer a revised and more nuanced understanding of the conditions under which sex chromosomes do, and do not, punch above their weight in the production of sexually dimorphic forms. Acknowledgments This work was supported by the BBSRC and the ERC (grant agreement 260233), and by a fellowship from the Wissenschaftskolleg zu Berlin to JEM and Lars Hiertas Minne to RD. We thank P.W. Harrison, S.H. Montgomery, J.C. Perry, F. Zimmer and A.E. Wright for helpful comments. References Albert, A.Y.K. & Otto, S.P. 2005. Sexual selection can resolve sex-linked antagonism. Science 310: 119–121. Andersson, M. 1994. Sexual Selection. Princeton University Press, Princeton. Arunkumar, K.P., Mita, K. & Nagaraju, J. 2009. The silkworm Z chromosome is enriched in testis-specific genes. Genetics 182: 493–501. Ayroles, A.F., Carbone, M.A., Stone, E.A., Jordan, K.W., Lyman, R.F., Magwire, M.M. et al. 2009. Systems genetics of complex traits in Drosophila melanogaster. Nat. Genet. 41: 299–307. Bachtrog, D. 2013. Y chromosome evolution: emerging insights into processes of Y chromosome degeneration. Nat. Rev. Genet. 14: 113–124. Bachtrog, D., Toda, N.R.T. & Lockton, S. 2010. Dosage compensation and demasculinization of X chromosomes in Drosophila. Curr. Biol. 20: 1476–1481. Badyaev, A.V. 2002. Growing apart: an ontogenetic perspective on the evolution of sexual size dimorphism. Trends Ecol. Evol. 17: 369–378. Carrel, L. & Willard, H.F. 2005. X inactivation profile reveals extensive variability in X-linked gene expression in females. Nature 434: 400–404. Castillo-Davis, C.I., Mekhedov, S.L., Hartl, D.L., Koonin, E.V. & Kondrashov, F.A. 2002. Selection for short introns in highly expressed genes. Nat. Genet. 31: 415–418. Charlesworth, B., Coyne, J.A. & Barton, N.H. 1987. The relative rates of evolution of sex chromosomes and autosomes. Am. Nat. 130: 113–146. Chase, K., Carrier, D.R., Adler, F.R., Ostrander, E.A. & Lark, K.G. 2005. Interaction between the X chromosome and an autosome regulations size sexual dimorphism in Portugese water dogs. Genome Res. 15: 1820–1824. Chenoweth, S.F. & Blows, M.W. 2003. Signal trait sexual dimorphism and mutual sexual selection in Drosophila serrata. Evolution 57: 2326–2334. Chenoweth, S.F., Rundle, H.D. & Blows, M.W. 2008. Genetic constraints and the evolution of display trait sexual dimorphism by natural and sexual selection. Am. Nat. 171: 22–34. Chippindale, A.K. & Rice, W.R. 2001. Y chromosome polymorphism is a strong determinant of male fitness in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 98: 5677–5682. Cocquet, J., Ellis, P.J.I., Yamauchi, Y., Mahadevaiah, S.K., Affara, N.A., Ward, M.A. et al. 2009. The multicopy gene Sly represses the sex chromosomes in the male mouse germline after meiosis. PLoS Biol. 7: ew1000244. Connallon, T. & Clark, A.G. 2010. Sex linkage, sex-specific selection and the role of recombination in the evolution of sexually dimorphic gene expression. Evolution 64: 3417–3442. Connallon, T. & Clark, A.G. 2011. Association between sexbiased gene expression and mutations with sex-specific phenotypic consequences in Drosophila. Genome Biol. Evol. 3: 151–155. Connallon, T. & Knowles, L.L. 2005. Intergenomic conflict revealed by patterns of sex-biased gene expression. Trends Genet. 21: 495–499. Cowley, D.E. & Atchley, W.R. 1988. Quantitative genetics of Drosophila melanogaster. II Heritabilities and genetic correlations between sexes for head and thorax traits. Genetics 119: 421–433. Cowley, D.E., Atchley, W.R. & Rutledge, J.J. 1986. Quantitative genetics of Drosophila melanogaster. I. Sexual dimorphism in genetic parameters for wing traits. Genetics 114: 549–566. Delph, L.F., Gehring, J.L., Frey, F.M., Arntz, A.M. & Levri, M. 2004. Genetics constraints on floral evolution in a sexually dimorphic plant revealed by artificial selection. Evolution 58: 1936–1946. Delph, L.F., Arntz, A.M., Scotti-Santagne, C. & Scotti, I. 2010. The genomic architecture of sexual dimorphism in the dioecious plant Silene latifolia. Evolution 64: 2873–2886. Delph, L.F., Steven, J.C., Anderson, I.A., Herlihy, C.R. & Bordie, E.D. 2011. Elimination of a genetic correlation between the sexes via artificial correlational selection. Evolution 65: 2872–2880. Fairbairn, D. 2013. Odd Couples: Extraordinary Differences Between the Sexes in the Animal Kingdom. Princeton University Press, Princeton. Fairbairn, D.J. & Roff, D.A. 2006. The quantitative genetics of sexual dimorphism: assessing the importance of sex linkage. Heredity 97: 319–328. Fitzpatrick, M.J. 2004. Pleiotropy and the genomic location of sexually selected genes. Am. Nat. 163: 800–808. Foerster, K., Coulson, T., Sheldon, B.C., Pemberton, J.M., Clutton-Brock, T.H. & Kruuk, L.E.B. 2007. Sexually antago- ª 2014 THE AUTHORS. J. EVOL. BIOL. 27 (2014) 1443–1453 JOURNAL OF EVOLUTIONARY BIOLOGY ª 2014 EUROPEAN SOCIETY FOR EVOLUTIONARY BIOLOGY Sex chromosomes and sexual dimorphism nistic genetic variation for fitness in red deer. Nature 447: 1107–1110. Fry, J.D. 2010. The genomic location of sexually antagonistic variation: some cautionary comments. Evolution 64: 1510– 1516. Gibson, J.R., Chippindale, A.K. & Rice, W.R. 2002. The X chromosome is a hot spot for sexually antagonistic fitness variation. Proc. Biol. Sci. 269: 499–505. Gordon, S.P., Lopez-Sepulcre, A. & Reznick, D.N. 2011. Predation-associated differences in sex linkage of wild guppy coloration. Evolution 66: 912–918. Grundberg, E., Small, K.S., Hedman, A.K., Nica, A.C., Buil, A., Keilson, S. et al. 2012. Mapping cis- and trans-regulatory effects across multiple tissues in twins. Nat. Genet. 44: 1084– 1089. Guioli, S., Lovell-Badge, R. & Turner, J.M.A. 2012. Errorprone pairing and no evidence for meiotic sex chromosome inactivation in chicken germ line. PLoS Genet. 8: e1002560. Guo, M., Davis, D. & Birchler, J.A. 1996. Dosage effects on gene expression in a maize ploidy series. Genetics 142: 1349– 1355. Haig, D. 2006. Self-imposed silence: parental antagonism and the evolution of X chromosome inactivation. Evolution 60: 440–447. Hense, W., Baines, J.F. & Parsch, J. 2007. X chromosome inactivation during Drosophila spermatogenesis. PLoS Biol. 5: 2288– 2295. Husby, A., Schielzeth, H., Forstmeier, W., Gustafsson, L. & Qvarnstr€ om, A. 2013. Sex chromosome linked genetic variance and the evolution of sexual dimorphism of quantitative traits. Evolution 67: 609–619. Innocenti, P. & Morrow, E. 2010. The sexually selected genes of Drosophila melanogaster. PLoS Biol. 8: e1000335. Iyengar, V.K., Reeve, K. & Eisner, T. 2002. Paternal inheritance of a female moth’s mating preference. Nature 419: 830–832. Jaquiery, J., Rispe, C., Roze, D., Legeai, F., Le Trionnaire, G., Stoeckel, S. et al. 2013. Masculinization of the X chromosome in the pea aphid. PLoS Genet. 9: e1003690. Khil, P.P., Smirnova, N.A., Romanienko, P.J. & CameriniOtero, R.D. 2004. The mouse X chromosome in enriched for sex-biased genes not subject to selection by meiotic sex chromosome inactivation. Nat. Genet. 36: 642–646. Kirkpatrick, M. & Hall, D.W. 2004. Sexual selection and sex linkage. Evolution 58: 683–691. Kitano, J., Ross, J.A., Mori, S., Kume, M., Jones, F.C., Chan, Y.F. et al. 2009. A role for a neo-sex chromosome in stickleback speciation. PLoS Genet. 461: 1079–1083. Knief, U., Schielzeth, H., Kenpanaers, B., Ellegren, H. & Forstmeier, W. 2012. QTL and quantitative genetic analysis of beak morphology reveals patterns of standing genetic variation in an Estrildid finch. Mol. Ecol. 21: 3704–3737. Lande, R. 1980. Sexual dimorphism, sexual selection and adaptation in polygenic characters. Evolution 34: 292–305. Lande, R. 1987. Genetic correlations between the sexes in the evolution of sexual dimorphism and mating preferences. In: Sexual Selection: Testing the Alternatives (J.W. Bradbury, M.B. Andersson, eds), pp. 83–94. John Wiley and Sons Ltd, New York. Lange, J., Skaletsky, H., can Daalen, S.K.M., Embry, S.L., Korver, C.M., Brown, L.G. et al. 2009. Isodicentric Y chromosomes and sex disorders as byproducts of homologous 1451 recombination that maintains palindromes. Cell 138: 855– 869. Lemos, B., Araripe, L.O. & Hartl, D.L. 2008. Polymorphic Y chromosomes harbour cryptic variation with manifold functional consequences. Science 319: 91–93. Li, Y., Lvarez, O.A.A., Gutteling, E.W., Tijsterman, M., Fu, J.J., Riksen, J.A.G. et al. 2006. Mapping determinants of gene expression plasticity by genetical genomics in C. elegans. PLoS Genet. 2: 2155–2161. Lindholm, A. & Breden, F. 2002. Sex chromosomes and sexual selection in poeciliid fishes. Am. Nat. 160: s214–s224. Magnusson, K., Lycett, G.J., Mendes, A.M., Lynd, A., Papathanos, P.A., Crisant, A. et al. 2012. Demasculinization of the Anopheles gambiae X chromosome. BMC Evol. Biol. 12: 69. Malone, J.H., Cho, D.Y., Mattiuzzo, N.R., Artieri, C.G., Jiang, L., Dale, R.K., et al. 2012. Mediation of Drosophila autosomal dosage effects and compensation by network interactions. Genome Biol. 13: R28. Mank, J.E. 2013. Sex chromosome dosage compensation: definitely not for everyone. Trends Genet. 12: 677–683. Mank, J.E. & Ellegren, H. 2009. Sex-linkage of sexually antagonistic genes is predicted by female-, but not male-, effects in birds. Evolution 63: 1464–1472. Mank, J.E., Hall, D.W., Kirkpatrick, M. & Avise, J.C. 2006. Sex chromosomes and male ornaments: a comparative evaluation in ray-finned fishes. Proc. Biol. Sci. 273: 233–236. Mank, J.E., Hultin-Rosenberg, L., Zwahlen, M. & Ellegren, H. 2008. Pleiotropic constraint hampers the resolution of sexual antagonism in vertebrate gene expression. Am. Nat. 171: 35– 43. Matson, C.K. & Zarkower, D. 2012. Sex and the singular DM domain: insights into sexual regulation, evolution and plasticity. Nat. Rev. Genet. 13: 163–174. Meiklejohn, C.D., Landeen, E.L., Cook, J.M., Kingan, S.B. & Presgraves, D.C. 2011. Sex chromosome specific regulation in the Drosophila male germline but little evidence for chromosome dosage compensation or meiotic inactivation. PLoS Biol. 9: e1001126. Meisel, R.P. 2011. Towards a more nuanced understanding of the relationship between sex-biased gene expression and rates of protein coding sequence evolution. Mol. Biol. Evol. 28: 1893–1900. Meisel, R.P., Malone, J.H. & Clark, A.G. 2012. Disentangling the relationship between sex-biased gene expression and sex-linkage. Genome Res. 22: 1255–1256. Merrill, R.M., Van Schooten, B., Scott, J.A. & Jiggins, C.D. 2011. Pervasive genetic associations between traits causing reproductive isolation in Heliconius butterflies. Proc. Biol. Sci. 278: 511–518. Moghadam, H.K., Pointer, M.A., Wright, A.E., Berlin, S. & Mank, J.E. 2012. W chromosome gene expression responds to female-specific selection. Proc. Natl. Acad. Sci. USA 109: 8207–8211. Natri, H.M., Shikano, T. & Merila, J. 2013. Progressive recombination suppression and differentiation in recently evolved neo-sex chromosomes. Mol. Biol. Evol. 30: 1131–1144. Ohno, S. 1967. Sex Chromosomes and Sex-Linked Genes. Springer Verlag, Berlin. 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: 697–700. ª 2014 THE AUTHORS. J. EVOL. BIOL. 27 (2014) 1443–1453 JOURNAL OF EVOLUTIONARY BIOLOGY ª 2014 EUROPEAN SOCIETY FOR EVOLUTIONARY BIOLOGY 1452 R. DEAN AND J. E. MANK Parnell, N.F. & Streelman, J.T. 2013. Genetic interactions controlling sex and color establish the potential for sexual conflict in Lake Malawi cichlids. Heredity 110: 239–246. Pointer, M.A., Harrison, P.W., Wright, A.E. & Mank, J.E. 2013. Masculinization of gene expression is associated with exaggeration of male sexual dimorphism. PLoS Genet. 9: e1003649. Poissant, J., Wilson, A.J. & Coltman, D.W. 2010. Sex-specific genetic variance and the evolution of sexual dimorphism: a systematic review of cross-sex genetic correlations. Evolution 64: 97–107. Poissant, J., Davis, C.S., Malenfant, R.M., Hogg, J.T. & Coltman, D.W. 2012. QTL mapping for sexually dimorphic fitness-related traits in wild bighorn sheep. Heredity 108: 256–263. Prince, E.G., Kirkland, D. & Demuth, J.P. 2010. Hyperexpression of the X chromosome in both sexes results in extensive female bias of X-Linked genes in the flour beetle. Genome Biol. Evol. 2: 336–346. Randall, J.C., Winkler, T.W., Kutalik, Z., Berndt, S.I., Jackson, A.U., Monda, K.L. et al. 2013. Sex stratified genome-wide association studies including 270 000 individuals show sexual dimorphism in genetic loci for anthropometric traits. PLoS Genet. 9: e1003500. Ranz, J.M., CAstillo-Davis, C.I., Meiklejohn, C.D. & Hartl, D.L. 2003. Sex-dependent gene expression and evolution of Drosophila transcriptome. Science 300: 1742–1745. Reeve, J.P. & Fairbairn, D.J. 2001. Predicting the evolution of sexual size dimorphism. J. Evol. Biol. 14: 244–254. Reeve, H.K. & Pfennig, D.W. 2003. Genetic biases for showy males: are some genetic systems especially conducive to sexual selection. Proc. Natl. Acad. Sci. USA 100: 1089–1094. Reinhold, K. 1998. Sex linkage among genes controlling sexually selected traits. Behav. Ecol. Sociobiol. 44: 1–7. Reinke, V., Gil, I.S., Ward, S. & Kazmer, K. 2004. Genomewide germline-enriched and sex-biased expression profiles in Caenorhabditis elegans. Development 131: 311–323. Rice, W.R. 1984. Sex chromosomes and the evolution of sexual dimorphism. Evolution 38: 735–742. Rice, W.R., Linder, J.E., Friberg, U., Lew, T.A., Morrow, E.H. & Stewart, A.D. 2005. Inter-locus antagonistic coevolution as an engine of speciation: assessment with hemiclonal analysis. Proc. Natl. Acad. Sci. USA 102(Suppl 1): 6527–6534. Roberts, R.B., Ser, J.R. & Kocher, T.D. 2009. Sexual conflict resolved by invasion of a novel sex determiner in Lake Malawi cichlids. Science 326: 998–1001. Rockman, M. 2012. The QTN program and the alleles that matter for evolution: all that’s gold does not glitter. Evolution 66: 1–17. Saether, S.A., Saetre, G.P., Borge, T., Wiley, C., Svedin, N., Andersson, G. et al. 2007. Sex chromosome-linked species recognition and evolution of reproductive isolation in flycatchers. Science 318: 95–97. Saetre, G.P., Borge, T., Lindroos, K., Haavie, J., Sheldon, B.C., Primmer, C. et al. 2003. Sex chromosome evolution and speciation in Ficedula flycatchers. Proc. Biol. Sci. 270: 53–59. Schielzeth, H., Kempenaers, B., Ellegren, H. & Forstmeier, W. 2012. QTL linkage mapping of zebra finch beak color shows an oligogenic control of a sexually selected trait. Evolution 66: 18–30. Scotti, I. & Delph, L.F. 2006. Selective trade-offs and sex chromosome evolution in Silene latifolia. Evolution 60: 1793– 1800. Shoenmakers, S., Wassenaar, E., Hoogerbrugge, J.W., Laven, J.S.E., Grootegoed, J.A. & Baarends, W.M. 2009. Female meiotic sex chromosome inactivation in chicken. PLoS Genet. 5: e1000466. Slate, J. 2013. From Beavis to beak color: a simulation study to examine how much QTL mapping can reveal about the genetic architecture of quantitative traits. Evolution 67: 1251–1262. Sturgill, D., Zhang, Y., Parisi, M. & Oliver, B. 2007. Demasculinization of X chromosomes in the Drosophila genus. Nature 450: 238–241. Subramanian, S. & Kumar, S. 2004. Gene expression intensity shapes evolutionary rates of proteins encoded by the vertebrate genome. Genetics 168: 373–381. Turner, J.M.A., Mahadevaiah, S.K., Fernandez-Capetillo, O., Nussenzweig, A., Xu, X.L., Deng, C.X. et al. 2005. Silencing of unsynapsed meiotic chromosomes in the mouse. Nat. Genet. 37: 41–47. Van Doorn, G.S. & Kirkpatrick, M. 2007. Turnover of sex chromosomes induced by sexual conflict. Nature 449: 909–912. Van Dyken, J.D. & Wade, M.J. 2010. The genetic signature of conditional expression. Genetics 184: 557–570. Van Nas, A., Ingram-Drake, L., Sinsheimer, J.S., Wang, S.S., Schadt, E.E., Drake, T. et al. 2010. Expression quantitative trait loci: replication, tissue- and sex-specificity in mice. Genetics 185: 1059–1068. Vibranovski, M.D., Zhang, Y.E., Kemkemer, C., Lopes, H.F., Karr, T.L. & Long, M. 2012. Re-analysis of the larval testis data on meiotic sex chromosome inactivation revealed evidence for tissue-specific gene expression related to the Drosophila X chromosome. BMC Biol. 10: 49. Vicoso, B. & Charlesworth, B. 2009. The deficit of male-biased genes on the D. melanogaster X chromosome is expression-dependent: a consequence of dosage compensation? J. Mol. Evol. 68: 576–583. Wayne, M.L., TElonis-Scott, M., Bono, L.M., Harshman, L., Kopp, A., Nuzhdin, S.V. et al. 2007. Simpler model of inheritance of transcriptional variation in male Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 104: 18577–18582. West, M.A.L., Kim, K., Kliebenstein, D.J., van Leeuwen, H., Michelmore, R.W., Doerge, R.W. et al. 2007. Global eQTL mapping reveals the complex genetic architecture of transcript-level variation in Arabidopsis. Genetics 175: 1441– 1450. Williams, G.C. 1957. Pleiotropy, natural selection and the evolution of senescence. Evolution 11: 398–411. Williams, T.M. & Carroll, S.B. 2009. Genetics and molecular insights into the development and evolution of sexual dimorphism. Nat. Rev. Genet. 10: 883–893. € 1922. One-sided masculine and sex-linked inheriWinge, O. tance in Lebistes reticulatus. J. Genet. 18: 1–43. Wolak, M.E. & Keller, L.F. 2014. Dominance genetic variance and inbreeding in natural populations. In: Quantitative Genetics in the Wild (A. Charmantier, D. Garant & L.E.B. Kruuk, eds), Chapter 7. Oxford University Press, Oxford. Wolfenbarger, L.L. & Wilkinson, G.S. 2001. Sex-linked expression of a sexually selected trait in the stalk-eyed fly, Cyrtodiopsis dalmanni. Evolution 55: 103–110. Wright, S. 1968. Evolution and the Genetics of Populations. Volume I: Genetic and Biometric Foundations. University of Chicago Press, Chicago. ª 2014 THE AUTHORS. J. EVOL. BIOL. 27 (2014) 1443–1453 JOURNAL OF EVOLUTIONARY BIOLOGY ª 2014 EUROPEAN SOCIETY FOR EVOLUTIONARY BIOLOGY Sex chromosomes and sexual dimorphism Wright, A.E., Moghadam, H.K. & Mank, J.E. 2012. Trade-off between selection for dosage compensation and masculinization of the avian Z chromosome. Genetics 192: 1433– 1445. Zhang, Y.E., Vibranovski, M.D., Landback, P., Marais, G.A.B. & Long, M.Y. 2010. Chromosomal redistribution of male-biased 1453 genes in mammalian evolution with two bursts of gene gain on the X chromosome. PLoS Biol. 8: e1000494. Received 26 September 2013; revised 20 January 2014; accepted 22 January 2014 ª 2014 THE AUTHORS. J. EVOL. BIOL. 27 (2014) 1443–1453 JOURNAL OF EVOLUTIONARY BIOLOGY ª 2014 EUROPEAN SOCIETY FOR EVOLUTIONARY BIOLOGY