Genetic conflict and changes in heterogametic mechanisms of sex determination

The consequences of cytoplasmic sex‐ratio distortion and host repression for the evolution of host sex‐determining mechanisms are examined. Analytical models and simulations are developed to investigate whether the interplay between sex‐ratio distorters and host masculinizers or resistance genes can cause heterogamety switching (changes between male and female heterogamety). Switches from female heterogamety to a system analogous to male heterogamety can occur when selection favours the spread of autosomal masculinizers. However, the evolutionary outcome depends on the type of repressor and costs associated with repression, and also on aspects of population structure. Under most conditions, systems evolved to a polymorphic sex‐determining state although many systems were characterized by numerical dominance of male heterogamety.     

How to identify sex chromosomes and their turnover

Although sex is a fundamental component of eukaryotic reproduction, the genetic systems that control sex determination are highly variable. In many organisms the presence of sex chromosomes is associated with female or male development. Although certain groups possess stable and conserved sex chromosomes, others exhibit rapid sex chromosome evolution, including transitions between male and female heterogamety, and turnover in the chromosome pair recruited to determine sex. These turnover events have important consequences for multiple facets of evolution, as sex chromosomes are predicted to play a central role in adaptation, sexual dimorphism, and speciation. However, our understanding of the processes driving the formation and turnover of sex chromosome systems is limited, in part because we lack a complete understanding of interspecific variation in the mechanisms by which sex is determined. New bioinformatic methods are making it possible to identify and characterize sex chromosomes in a diverse array of non‐model species, rapidly filling in the numerous gaps in our knowledge of sex chromosome systems across the tree of life. In turn, this growing data set is facilitating and fueling efforts to address many of the unanswered questions in sex chromosome evolution. Here, we synthesize the available bioinformatic approaches to produce a guide for characterizing sex chromosome system and identity simultaneously across clades of organisms. Furthermore, we survey our current understanding of the processes driving sex chromosome turnover, and highlight important avenues for future research.     

ZW,XY, and yet ZW: Sex chromosome evolution in snakes even more complicated

Snakes are historically important in the formulation of several central concepts on the evolution of sex chromosomes. For over 50 years, it was believed that all snakes shared the same ZZ/ZW sex chromosomes, which are homomorphic and poorly differentiated in “basal” snakes such as pythons and boas, while heteromorphic and well differentiated in “advanced” (caenophidian) snakes. Recent molecular studies revealed that differentiated sex chromosomes are indeed shared among all families of caenophidian snakes, but that boas and pythons evolved likely independently male heterogamety (XX/XY sex chromosomes). The historical report of heteromorphic ZZ/ZW sex chromosomes in a boid snake was previously regarded as ambiguous. In the current study, we document heteromorphic ZZ/ZW sex chromosomes in a boid snake. A comparative approach suggests that these heteromorphic sex chromosomes evolved very recently and that they are poorly differentiated at the sequence level. Interestingly, two snake lineages with confirmed male heterogamety possess homomorphic sex chromosomes, but heteromorphic sex chromosomes are present in both snake lineages with female heterogamety. We point out that this phenomenon is more common across squamates. The presence of female heterogamety in non‐caenophidian snakes indicates that the evolution of sex chromosomes in this lineage is much more complex than previously thought, making snakes an even better model system for the evolution of sex chromosomes.     

Identification of sex‐specific molecular markers using restriction site‐associated DNA sequencing

A major barrier to evolutionary studies of sex determination and sex chromosomes has been a lack of information on the types of sex‐determining mechanisms that occur among different species. This is particularly problematic in groups where most species lack visually heteromorphic sex chromosomes, such as fish, amphibians and reptiles, because cytogenetic analyses will fail to identify the sex chromosomes in these species. We describe the use of restriction site‐associated DNA (RAD) sequencing, or RAD‐seq, to identify sex‐specific molecular markers and subsequently determine whether a species has male or female heterogamety. To test the accuracy of this technique, we examined the lizard Anolis carolinensis. We performed RAD‐seq on seven male and ten female A. carolinensis and found one male‐specific molecular marker. Anolis carolinensis has previously been shown to possess male heterogamety and the recently published A. carolinensis genome facilitated the characterization of the sex‐specific RAD‐seq marker. We validated the male specificity of the new marker using PCR on additional individuals and also found that it is conserved in some other Anolis species. We discuss the utility of using RAD‐seq to identify sex‐determining mechanisms in other species with cryptic or homomorphic sex chromosomes and the implications for the evolution of male heterogamety in Anolis.     

Genetic sex determination mechanisms and evolution.

Different animal groups exhibit a surprisingly diversity of sex determination systems. Moreover, even systems that are superficially similar may utilize different underlying mechanisms. This diversity is illustrated by a comparison of sex determination in three well-studied model organisms: the fruitfly Drosophila melanogaster, the nematode Caenorhabditis elegans, and the mouse. All three animals exhibit male heterogamety, extensive sexual dimorphism and sex chromosome dosage compensation, yet the molecular and cellular processes involved are now known to be quite unrelated. The similarities must have arisen by convergent evolution. Studies of sex determination demonstrate that evolution can produce a variety of solutions to the same basic problems in development.     

Plant sex determination and sex chromosomes

Sex determination systems in plants have evolved many times from hermaphroditic ancestors (including monoecious plants with separate male and female flowers on the same individual), and sex chromosome systems have arisen several times in flowering plant evolution. Consistent with theoretical models for the evolutionary transition from hermaphroditism to monoecy, multiple sex determining genes are involved, including male-sterility and female-sterility factors. The requirement that recombination should be rare between these different loci is probably the chief reason for the genetic degeneration of Y chromosomes. Theories for Y chromosome degeneration are reviewed in the light of recent results from genes on plant sex chromosomes.     

Sex ratio selection and multi-factorial sex determination in the housefly: a dynamic model

Sex determining (SD) mechanisms are highly variable between different taxonomic groups and appear to change relatively quickly during evolution. Sex ratio selection could be a dominant force causing such changes. We investigate theoretically the effect of sex ratio selection on the dynamics of a multi-factorial SD system. The system considered resembles the naturally occurring three-locus system of the housefly, which allows for male heterogamety, female heterogamety and a variety of other mechanisms. Sex ratio selection is modelled by assuming cost differences in the production of sons and daughters, a scenario leading to a strong sex ratio bias in the absence of constraints imposed by the mechanism of sex determination. We show that, despite of the presumed flexibility of the SD system considered, equilibrium sex ratios never deviate strongly from 1 : 1. Even if daughters are very costly, a male-biased sex ratio can never evolve. If sons are more costly, sex ratio can be slightly female biased but even in case of large cost differences the bias is very small (<10% from 1 : 1). Sex ratio selection can lead to a shift in the SD mechanism, but cannot be the sole cause of complete switches from one SD system to another. In fact, more than one locus remains polymorphic at equilibrium. We discuss our results in the context of evolution of the variable SD mechanism found in natural housefly populations.     

Bird sex determination

During the evolution, sex determination occurred early. Sex determining factors were progressively isolated from other genes in sexual chromosomes, or gonosomes. Among vertebrates, evolution took two opposite pathways : in mammals, the system of XX:XY sex determination, with Y chromosome, induces male differentiation. In contrast, in birds, the system ZZ:ZW, with the W chromosome, induces female differentiation. But comparative studies show that the two pathways are not so simple. In the chicken as in the lower vertebrates, estrogens play a central role in gonadal sex differentiation. Several genes, show to be critical for mammalian determination, are also expressed in the chicken but their expression pattern differs, indicating functional plasticity. The W-linked female determinants remains still unknown. But comparative studies of the two pathways, with conserved and divergent elements, are broadening our understanding of sex determination.     

Invasion and fixation of sex-reversal genes

We simulated a meta-population with random dispersal among demes but local mating within demes to investigate conditions under which a dominant female-determining gene W, with no individual selection advantage, can invade and become fixed in females, changing the population from male to female heterogamety. Starting with one mutant W in a single deme, the interaction of sex ratio selection and random genetic drift causes W to be fixed among females more often than a comparable neutral mutation with no influence on sex determination, even when YY males have slightly reduced viability. Meta-population structure and interdeme selection can also favour the fixation of W. The reverse transition from female to male heterogamety can also occur with higher probability than for a comparable neutral mutation. These results help to explain the involvement of sex-determining genes in the evolution of sex chromosomes and in sexual selection and speciation.     

Morphologically differentiated sex chromosomes in neotropical freshwater fish

A general survey of the occurrence of morphologically differentiated sex chromosomes in the neotropical freshwater fishes is presented. The total number of 32 occurrences involving simple XX-XY and ZZ-ZW, and multiple X₁X₂Y, XY₁Y₂ and ZW₁W₂ sex chromosome systems is described, with comments on the aspects of sex chromosome evolution in this fish fauna. The occurrence of different sex chromosome systems in related species of the same genus, or in different populations of the same nominal species, involving male and sometimes female heterogamety, and differences in the molecular composition of sex-linked heterochromatin, are considered as indicative of the early stage of sex chromosomes evolution in fish.     

Genetic mapping of sex determination in a wild strawberry, Fragaria virginiana, reveals earliest form of sex chromosome

The evolution of separate sexes (dioecy) from hermaphroditism is one of the major evolutionary transitions in plants, and this transition can be accompanied by the development of sex chromosomes. Studies in species with intermediate sexual systems are providing unprecedented insight into the initial stages of sex chromosome evolution. Here, we describe the genetic mechanism of sex determination in the octoploid, subdioecious wild strawberry, Fragaria virginiana Mill., based on a whole-genome simple sequence repeat (SSR)-based genetic map and on mapping sex determination as two qualitative traits, male and female function. The resultant total map length is 2373 cM and includes 212 markers on 42 linkage groups (mean marker spacing: 14 cM). We estimated that approximately 70 and 90% of the total F. virginiana genetic map resides within 10 and 20 cM of a marker on this map, respectively. Both sex expression traits mapped to the same linkage group, separated by approximately 6 cM, along with two SSR markers. Together, our phenotypic and genetic mapping results support a model of gender determination in subdioecious F. virginiana with at least two linked loci (or gene regions) with major effects. Reconstruction of parental genotypes at these loci reveals that both female and hermaphrodite heterogamety exist in this species. Evidence of recombination between the sex-determining loci, an important hallmark of incipient sex chromosomes, suggest that F. virginiana is an example of the youngest sex chromosome in plants and thus a novel model system for the study of sex chromosome evolution.     

Dynamic sex chromosomes in Old World chameleons (Squamata: Chamaeleonidae)

Much of our current state of knowledge concerning sex chromosome evolution is based on a handful of ‘exceptional’ taxa with heteromorphic sex chromosomes. However, classifying the sex chromosome systems of additional species lacking easily identifiable, heteromorphic sex chromosomes is indispensable if we wish to fully understand the genesis, degeneration and turnover of vertebrate sex chromosomes. Squamate reptiles (lizards and snakes) are a potential model clade for studying sex chromosome evolution as they exhibit a suite of sex‐determining modes yet most species lack heteromorphic sex chromosomes. Only three (of 203) chameleon species have identified sex chromosome systems (all with female heterogamety, ZZ/ZW). This study uses a recently developed method to identify sex‐specific genetic markers from restriction site‐associated DNA sequence (RADseq) data, which enables the identification of sex chromosome systems in species lacking heteromorphic sex chromosomes. We used RADseq and subsequent PCR validation to identify an XX/XY sex chromosome system in the veiled chameleon (Chamaeleo calyptratus), revealing a novel transition in sex chromosome systems within the Chamaeleonidae. The sex‐specific genetic markers identified here will be essential in research focused on sex‐specific, comparative, functional and developmental evolutionary questions, further promoting C. calyptratus’ utility as an emerging model organism.     

When Sex Chromosomes Recombine Only in the Heterogametic Sex: Heterochiasmy and Heterogamety in Hyla Tree Frogs

Sex chromosomes are classically predicted to stop recombining in the heterogametic sex, thereby enforcing linkage between sex-determining (SD) and sex-antagonistic (SA) genes. With the same rationale, a pre-existing sex asymmetry in recombination is expected to affect the evolution of heterogamety, for example, a low rate of male recombination might favor transitions to XY systems, by generating immediate linkage between SD and SA genes. Furthermore, the accumulation of deleterious mutations on nonrecombining Y chromosomes should favor XY-to-XY transitions (which discard the decayed Y), but disfavor XY-to-ZW transitions (which fix the decayed Y as an autosome). Like many anuran amphibians, Hyla tree frogs have been shown to display drastic heterochiasmy (males only recombine at chromosome tips) and are typically XY, which seems to fit the above expectations. Instead, here we demonstrate that two species, H. sarda and H. savignyi, share a common ZW system since at least 11 Ma. Surprisingly, the typical pattern of restricted male recombination has been maintained since then, despite female heterogamety. Hence, sex chromosomes recombine freely in ZW females, not in ZZ males. This suggests that heterochiasmy does not constrain heterogamety (and vice versa), and that the role of SA genes in the evolution of sex chromosomes might have been overemphasized.     

Genomic evidence for a large-Z effect

The 'large-X effect' suggests that sex chromosomes play a disproportionate role in adaptive evolution. Theoretical work indicates that this effect may be most pronounced in genetic systems with female heterogamety under both good-genes and Fisher's runaway models of sexual selection (males ZZ, females ZW). Here, I use a comparative genomic approach (alignments of several thousands of chicken-zebra finch-human-mouse-opossum orthologues) to show that avian Z-linked genes are highly overrepresented among those bird-mammalian orthologues that show evidence of accelerated rate of functional evolution in birds relative to mammals; the data suggest a twofold excess of such genes on the Z chromosome. A reciprocal analysis of genes accelerated in mammals found no evidence for an excess of X-linkage. This would be compatible with theoretical expectations for differential selection on sex-linked genes under male and female heterogamety, although the power in this case was not sufficient to statistically show that 'large-Z' was more pronounced than 'large-X'. Accelerated Z-linked genes include a variety of functional categories and are characterized by higher non-synonymous to synonymous substitution rate ratios than both accelerated autosomal and non-accelerated genes. This points at a genomic 'large-Z effect', which is widespread and of general significance for adaptive divergence in birds.     

Maternal-offspring conflict leads to the evolution of dominant zygotic sex determination

Sex determination in many species involves interactions among maternally expressed genes (eg, mRNA's and proteins placed into the egg) and zygotically expressed genes. Recent studies have proposed that conflicting selective pressures can occur between maternally and zygotically expressed sex determining loci and that these may play a role in shaping the evolution of sex determining systems. Here we show that such genetic conflict occurs under very general circumstances. Whenever sex ratio among progeny in a family affects the fitness of either progeny in that family or maternal fitness, then maternal-zygotic genetic conflict occurs. Furthermore, we show that this conflict typically results in a "positive feedback loop" that leads to the evolution of a dominant zygotic sex determining locus. When males more negatively effect fitness within the family, a male heterogametic (XY male) sex determining system evolves, whereas when females more negatively effect fitness in the family, a female heterogametic (ZW female) system evolves. Individuals with the dominant sex allele are one sex, and the opposite sex is determined by maternally-expressed genes in individuals without the dominant sex allele. Results therefore suggest that maternal-zygotic conflict could play a role in the early evolution of chromosomal sex determining systems. Predictions are made concerning the patterns of expression of maternal and zygotic sex determining genes expected to result from conflict over sex determination.     

The red bayberry genome and genetic basis of sex determination

Morella rubra, red bayberry, is an economically important fruit tree in south China. Here, we assembled the first high‐quality genome for both a female and a male individual of red bayberry. The genome size was 313‐Mb, and 90% sequences were assembled into eight pseudo chromosome molecules, with 32 493 predicted genes. By whole‐genome comparison between the female and male and association analysis with sequences of bulked and individual DNA samples from female and male, a 59‐Kb region determining female was identified and located on distal end of pseudochromosome 8, which contains abundant transposable element and seven putative genes, four of them are related to sex floral development. This 59‐Kb female‐specific region was likely to be derived from duplication and rearrangement of paralogous genes and retained non‐recombinant in the female‐specific region. Sex‐specific molecular markers developed from candidate genes co‐segregated with sex in a genetically diverse female and male germplasm. We propose sex determination follow the ZW model of female heterogamety. The genome sequence of red bayberry provides a valuable resource for plant sex chromosome evolution and also provides important insights for molecular biology, genetics and modern breeding in Myricaceae family.     

Meiotic pairing constraints and the activity of sex chromosomes

The state of activity and condensation of the sex chromosomes in gametocytes is frequently different from that found in somatic cells. For example, whereas the X chromosomes of XY males are euchromatic and active in somatic cells, they are usually condensed and inactive at the onset of meiosis; in the somatic cells of female mammals, one X chromosome is heterochromatic and inactive, but both X chromosomes are euchromatic and active early in meiosis. In species in which the female is the heterogametic sex (ZZ males and ZW females), the W chromosome, which is often seen as a condensed chromatin body in somatic cells, becomes euchromatic in early oocytes. We describe an hypothesis which can explain these changes in the activity and condensation of sex chromosomes in gametocytes. It is based on the fact that normal chromosome pairing seems to be essential for the survival of sex cells; chromosomal anomalies resulting in incomplete pairing during meiosis usually result in gametogenic loss. We argue that the changes seen in the sex chromosomes reflect the need to avoid pairing failure during meiosis. Pairing normally requires structural and conformational homology of the two chromosomes, but when the regions is avoided when these regions become heterochromatinized. This hypothesis provides an explanation for the changes found in gametocytes both in species with male heterogamety and those with female heterogamety. It also suggests possible reasons for the frequent origin of large supernumerary chromosomes from sex chromosomes, and for the reported lack of dosage compensation in species with female heterogamety.     

Retrogenes Moved Out of the Z Chromosome in the Silkworm

Previous studies on organisms with well-differentiated X and Y chromosomes, such as Drosophila and mammals, consistently detected an excess of genes moving out of the X chromosome and gaining testis-biased expression. Several selective evolutionary mechanisms were shown to be associated with this nonrandom gene traffic, which contributed to the evolution of the X chromosome and autosomes. If selection drives gene traffic, such traffic should also exist in species with Z and W chromosomes, where the females are the heterogametic sex. However, no previous studies on gene traffic in species with female heterogamety have found any nonrandom chromosomal gene movement. Here, we report an excess of retrogenes moving out of the Z chromosome in an organism with the ZW sex determination system, Bombyx mori. In addition, we showed that those "out of Z" retrogenes tended to have ovary-biased expression, which is consistent with the pattern of non-retrogene traffic recently reported in birds and symmetrical to the retrogene movement in mammals and fruit flies out of the X chromosome evolving testis functions. These properties of gene traffic in the ZW system suggest a general role for the heterogamety of sex chromosomes in determining the chromosomal locations and the evolution of sex-biased genes.     

Novel evolutionary pathways of sex‐determining mechanisms

Evolutionary transitions between sex‐determining mechanisms (SDMs) are an enigma. Among vertebrates, individual sex (male or female) is primarily determined by either genes (genotypic sex determination, GSD) or embryonic incubation temperature (temperature‐dependent sex determination, TSD), and these mechanisms have undergone repeated evolutionary transitions. Despite this evolutionary lability, transitions from GSD (i.e. from male heterogamety, XX/XY, or female heterogamety, ZZ/ZW) to TSD are an evolutionary conundrum, as they appear to require crossing a fitness valley arising from the production of genotypes with reduced viability owing to being homogametic for degenerated sex chromosomes (YY or WW individuals). Moreover, it is unclear whether alternative (e.g. mixed) forms of sex determination can persist across evolutionary time. It has previously been suggested that transitions would be easy if temperature‐dependent sex reversal (e.g. XX male or XY female) was asymmetrical, occurring only in the homogametic sex. However, only recently has a mechanistic model of sex determination emerged that may allow such asymmetrical sex reversal. We demonstrate that selection for TSD in a realistic sex‐determining system can readily drive evolutionary transitions from GSD to TSD that do not require the production of YY or WW individuals. In XX/XY systems, sex reversal (female to male) occurs in a portion of the XX individuals only, leading to the loss of the Y allele (or chromosome) from the population as XX individuals mate with each other. The outcome is a population of XX individuals whose sex is determined by incubation temperature (TSD). Moreover, our model reveals a novel evolutionarily stable state representing a mixed‐mechanism system that has not been revealed by previous approaches. This study solves two long‐standing puzzles of the evolution of sex‐determining mechanisms by illuminating the evolutionary pathways and endpoints.     

Weak male-determining genes and female heterogamety in Chironomus tentans

Female heterogamety in the midge Chironomus tentans has been previously reported and attributed to a dominant female determiner. Published results are not consistent with the interpretation, and the female heterogamety, if any, can be better explained by a model involving a weakened male determiner. Suggestions are made for crosses between populations with different sex-determining mechanisms that would discriminate between models for the evolution of female heterogamety, and serve to determine whether indeed female development is the norm in the absence of any parental sex chromosomes.