A single theory for the evolution of sex chromosomes and the two rules of speciation

Abstract

Sex chromosomes are involved in three major empirical patterns: Y (or W) chromosomes are often non-recombining and degenerate; heterogametic offspring (XY or ZW) from interspecific crosses are more often sterile or inviable than homogametic offspring (Haldanes rule); the X (or Z) has a disproportionately large effect on reproductive isolation between species compared to autosomes (the large X effect). Each observation has received its own tailored explanation involving multiple genetic and evolutionary causes. Here, we show that these empirical patterns all emerge from a single theory for sex chromosome evolution incorporating the co-evolution of cis and trans-acting regulators of gene expression, and leading to systematic misexpression of dosage-compensated genes in heterogametic F1 hybrids, for both young and old sex chromosomes. Structured AbstractO_ST_ABSIntroductionC_ST_ABSSex chromosomes have long been known to play a prominent role in the genetics of speciation, captured by the famous "two rules of speciation". The first, attributed to J.B.S. Haldane and known as Haldanes rule, corresponds to the general observation that when, among interspecific hybrids, one sex is inviable or sterile, it is more often the heterogametic sex (XY or ZW). The second is known as the large X effect, and refers to the fact that the X or Z chromosome often has a stronger effect on hybrid fitness than autosomes of equivalent size. While several theories have been proposed to explain these empirical patterns, none has been able to account for all the observations, leading to the current consensus that the two rules of speciation may have multiple causes. Furthermore, these theories remain disconnected from general models predicting sex chromosome evolution. RationaleWe have recently developed a new theory for the evolution of sex chromosomes, showing that the coevolution of cis and trans regulators of gene expression can lead to stable recombination arrest between the X and Y (or Z and W) chromosomes, degeneration of the Y (or W) chromosome and dosage compensation. Here we investigate the role of sex chromosomes on the fitness of interspecific hybrids under this general model, considering different scenarios that correspond to different stages in the evolution of sex chromosomes. We also investigate the effect of genes with sex-specific effects that affect either male or female fertility. ResultsHaldanes rule and the large X effect are observed in all scenarios considered. Our model also captures "Darwins corollary" to Haldanes rule, i.e. an asymmetry between the effects of reciprocal crosses between species. These results are caused by the divergence of regulators of gene expression between species, due to the presence of a non-recombining, degenerate stratum on the Y chromosome either shared by both species or present in only one of them. In both cases, Haldanes rule results from the heterogametic sex inheriting X chromosome cis regulators from only one parental species that have not coevolved with the trans regulators of the other species, resulting in under or overexpression of dosage-compensated genes on the X (or Z) chromosome. While this regulatory divergence may be limited in the case of species with a global (chromosome-wide) somatic system of dosage compensation, regulatory divergence of germline-expressed genes may generate Haldanes rule for fertility in these species. Genes whose effect is restricted to the heterogametic sex often have strong effects on reproductive isolation and on the fitness of heterogametic hybrids, especially if they are silenced on the X (or Z) chromosome of one parental species and on the Y (or W) chromosome of the other. ConclusionOur study shows that a simple model of coevolution between cis and trans regulators of gene expression on sex chromosomes can explain the evolution of non-recombining, degenerate and dosage compensated Y and W chromosomes, Haldanes rule and the large X effect. It may also explain why Haldanes rule is based on viability is some taxa and on fertility in others, an observation that remained difficult to explain from previous theories. These results match with recent observations on the role of misregulation of gene expression on hybrid fitness, and open new perspectives of empirical research on the genetics of speciation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=184 SRC="FIGDIR/small/585601v4_figa1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@e94472org.highwire.dtl.DTLVardef@8cbecaorg.highwire.dtl.DTLVardef@41cc5dorg.highwire.dtl.DTLVardef@1d00ea0_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOSummary figure.C_FLOATNO A multilocus, individual-based simulation model was used to investigate the joint evolution of sex chromosomes and reproductive isolation between species. It includes deleterious mutations, mutations suppressing or restoring recombination and mutations affecting the strength of cis and trans regulators of gene expression. This model predicts the major features of sex chromosome evolution and the "two rules of speciation" (Haldanes rule and the large X effect). C_FIG