Evolution of the avian sex chromosomes and their role in sex determination

Is it the female-specific W chromosome of birds that causes the avian embryo to develop a female phenotype, analogous to the dominance mode of genic sex differentiation seen in mammals? Or is it the number of Z chromosomes that triggers male development, similar to the balance mode of differentiation seen in Drosophila and Caenorhabditis elegans? Although definite answers to these questions cannot be given yet, some recent data have provided support for the latter hypothesis. Moreover, despite the potentially common features of sex determination in mammals and birds, comparative mapping shows that the avian sex chromosomes have a different autosomal origin than the mammalian X and Y chromosomes.     

The “unguarded‐X” and the genetic architecture of lifespan: Inbreeding results in a potentially maladaptive sex‐specific reduction of female lifespan in Drosophila melanogaster

Sex differences in ageing and lifespan are ubiquitous in nature. The "unguarded‐X” hypothesis (UXh) suggests they may be partly due to the expression of recessive mutations in the hemizygous sex chromosomes of the heterogametic sex, which could help explain sex‐specific ageing in a broad array of taxa. A prediction central to the UX hypothesis is that inbreeding will decrease the lifespan of the homogametic sex more than the heterogametic sex, because only in the former does inbreeding increase the expression of recessive deleterious mutations. In this study, we test this prediction by examining the effects of inbreeding on the lifespan and fitness of male and female Drosophila melanogaster across different social environments. We found that, across social environments, inbreeding resulted in a greater reduction of female than male lifespan, and that inbreeding effects on fitness did not seem to counterbalance sex‐specific effects on lifespan, suggesting the former are maladaptative. Inter‐ and intra‐sexual correlation analyses also allowed us to identify evidence of an underlying joint genetic architecture for inbreeding effects on lifespan. We discuss these results in light of the UXh and other alternative explanations, and suggest that more attention should be paid to the possibility that the “unguarded‐X” may play an important role in the evolution of sex‐specific lifespan.     

Sex differences in life span: Females homozygous for the X chromosome do not suffer the shorter life span predicted by the unguarded X hypothesis

Life span differs between the sexes in many species. Three hypotheses to explain this interesting pattern have been proposed, involving different drivers: sexual selection, asymmetrical inheritance of cytoplasmic genomes, and hemizygosity of the X(Z) chromosome (the unguarded X hypothesis). Of these, the unguarded X has received the least experimental attention. This hypothesis suggests that the heterogametic sex suffers a shortened life span because recessive deleterious alleles on its single X(Z) chromosome are expressed unconditionally. In Drosophila melanogaster, the X chromosome is unusually large (～20% of the genome), providing a powerful model for evaluating theories involving the X. Here, we test the unguarded X hypothesis by forcing D. melanogaster females from a laboratory population to express recessive X‐linked alleles to the same degree as males, using females exclusively made homozygous for the X chromosome. We find no evidence for reduced life span or egg‐to‐adult viability due to X homozygozity. In contrast, males and females homozygous for an autosome both suffer similar, significant reductions in those traits. The logic of the unguarded X hypothesis is indisputable, but our results suggest that the degree to which recessive deleterious X‐linked alleles depress performance in the heterogametic sex appears too small to explain general sex differences in life span.     

Dosage compensation in birds

The Z and W sex chromosomes of birds have evolved independently from the mammalian X and Y chromosomes [1]. Unlike mammals, female birds are heterogametic (ZW), while males are homogametic (ZZ). Therefore male birds, like female mammals, carry a double dose of sex-linked genes relative to the other sex. Other animals with nonhomologous sex chromosomes possess "dosage compensation" systems to equalize the expression of sex-linked genes. Dosage compensation occurs in animals as diverse as mammals, insects, and nematodes, although the mechanisms involved differ profoundly [2]. In birds, however, it is widely accepted that dosage compensation does not occur [3-5], and the differential expression of Z-linked genes has been suggested to underlie the avian sex-determination mechanism [6]. Here we show equivalent expression of at least six of nine Z chromosome genes in male and female chick embryos by using real-time quantitative PCR [7]. Only the Z-linked ScII gene, whose ortholog in Caenorhabditis elegans plays a crucial role in dosage compensation [8], escapes compensation by this assay. Our results imply that the majority of Z-linked genes in the chicken are dosage compensated.     

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.     

POSITIVE SELECTION DRIVES FASTER‐Z EVOLUTION IN SILKMOTHS

Genes linked to X or Z chromosomes, which are hemizygous in the heterogametic sex, are predicted to evolve at different rates than those on autosomes. This “faster‐X effect” can arise either as a consequence of hemizygosity, which leads to more efficient selection for recessive beneficial mutations in the heterogametic sex, or as a consequence of reduced effective population size of the hemizygous chromosome, which leads to increased fixation of weakly deleterious mutations due to genetic drift. Empirical results to date suggest that, while the overall pattern across taxa is complicated, systems with male heterogamy show a faster‐X effect attributable to more efficient selection, whereas the faster‐Z effect in female‐heterogametic taxa is attributable to increased drift. To test the generality of the faster‐Z pattern seen in birds and snakes, we sequenced the genome of the lepidopteran silkmoth Bombyx huttoni. We show that silkmoths experience faster‐Z evolution, but unlike in birds and snakes, the faster‐Z effect appears to be attributable to more efficient positive selection. These results suggest that female heterogamy alone is unlikely to explain the reduced efficacy of selection on vertebrate Z chromosomes. It is likely that many factors, including differences in overall effective population size, influence Z chromosome evolution.     

Origin and evolution of mammalian sex chromosomes

Mammals present an XX/XY system of chromosomal sex determination, males being the heterogametic sex. Comparative studies of the gene content of sex chromosomes from the major groups of mammals reveal that most Y genes have X-linked homologues and that X and Y share homologous pseudoautosomal regions. These observations, together with the presence of the two homologous regions (pseudoautosomal regions) at the tips of the sex chromosomes, suggest that these chromosomes began as an ordinary pair of homologous autosomes. Birds present a ZW/ZZ system of chromosomal sex determination where females are the heterogametic sex. In this case, avian sex chromosomes are derived from different pairs of autosomes than mammals. The evolutionary pathway from the autosomal homomorphic departure to the present-day heteromorphic sex chromosomes in mammals includes suppression of X-Y recombination, differentiation of the nascent non-recombining regions, and progressive autosomal addition and attrition of the sex chromosomes. Recent results indicate that the event marking the beginning of the differentiation between the extant X and Y chromosomes occurred about 300 million years ago.     

Sex chromosomes evolved from independent ancestral linkage groups in winged insects

The evolution of a pair of chromosomes that differ in appearance between males and females (heteromorphic sex chromosomes) has occurred repeatedly across plants and animals. Recent work has shown that the male heterogametic (XY) and female heterogametic (ZW) sex chromosomes evolved independently from different pairs of homomorphic autosomes in the common ancestor of birds and mammals but also that X and Z chromosomes share many convergent molecular features. However, little is known about how often heteromorphic sex chromosomes have either evolved convergently from different autosomes or in parallel from the same pair of autosomes and how universal patterns of molecular evolution on sex chromosomes really are. Among winged insects with sequenced genomes, there are male heterogametic species in both the Diptera (e.g., Drosophila melanogaster) and the Coleoptera (Tribolium castaneum), female heterogametic species in the Lepidoptera (Bombyx mori), and haplodiploid species in the Hymenoptera (e.g., Nasonia vitripennis). By determining orthologous relationships among genes on the X and Z chromosomes of insects with sequenced genomes, we are able to show that these chromosomes are not homologous to one another but are homologous to autosomes in each of the other species. These results strongly imply that heteromorphic sex chromosomes have evolved independently from different pairs of ancestral chromosomes in each of the insect orders studied. We also find that the convergently evolved X chromosomes of Diptera and Coleoptera share genomic features with each other and with vertebrate X chromosomes, including excess gene movement from the X to the autosomes. However, other patterns of molecular evolution--such as increased codon bias, decreased gene density, and the paucity of male-biased genes on the X--differ among the insect X and Z chromosomes. Our results provide evidence for both differences and nearly universal similarities in patterns of evolution among independently derived sex chromosomes.     

The Staurotypus Turtles and Aves Share the Same Origin of Sex Chromosomes but Evolved Different Types of Heterogametic Sex Determination

Reptiles have a wide diversity of sex-determining mechanisms and types of sex chromosomes. Turtles exhibit temperature-dependent sex determination and genotypic sex determination, with male heterogametic (XX/XY) and female heterogametic (ZZ/ZW) sex chromosomes. Identification of sex chromosomes in many turtle species and their comparative genomic analysis are of great significance to understand the evolutionary processes of sex determination and sex chromosome differentiation in Testudines. The Mexican giant musk turtle (Staurotypus triporcatus, Kinosternidae, Testudines) and the giant musk turtle (Staurotypus salvinii) have heteromorphic XY sex chromosomes with a low degree of morphological differentiation; however, their origin and linkage group are still unknown. Cross-species chromosome painting with chromosome-specific DNA from Chinese soft-shelled turtle (Pelodiscus sinensis) revealed that the X and Y chromosomes of S. triporcatus have homology with P. sinensis chromosome 6, which corresponds to the chicken Z chromosome. We cloned cDNA fragments of S. triporcatus homologs of 16 chicken Z-linked genes and mapped them to S. triporcatus and S. salvinii chromosomes using fluorescence in situ hybridization. Sixteen genes were localized to the X and Y long arms in the same order in both species. The orders were also almost the same as those of the ostrich (Struthio camelus) Z chromosome, which retains the primitive state of the avian ancestral Z chromosome. These results strongly suggest that the X and Y chromosomes of Staurotypus turtles are at a very early stage of sex chromosome differentiation, and that these chromosomes and the avian ZW chromosomes share the same origin. Nonetheless, the turtles and birds acquired different systems of heterogametic sex determination during their evolution.     

The origin and evolution of vertebrate sex chromosomes and dosage compensation

In mammals, birds, snakes and many lizards and fish, sex is determined genetically (either male XY heterogamy or female ZW heterogamy), whereas in alligators, and in many reptiles and turtles, the temperature at which eggs are incubated determines sex. Evidently, different sex-determining systems (and sex chromosome pairs) have evolved independently in different vertebrate lineages. Homology shared by Xs and Ys (and Zs and Ws) within species demonstrates that differentiated sex chromosomes were once homologous, and that the sex-specific non-recombining Y (or W) was progressively degraded. Consequently, genes are left in single copy in the heterogametic sex, which results in an imbalance of the dosage of genes on the sex chromosomes between the sexes, and also relative to the autosomes. Dosage compensation has evolved in diverse species to compensate for these dose differences, with the stringency of compensation apparently differing greatly between lineages, perhaps reflecting the concentration of genes on the original autosome pair that required dosage compensation. We discuss the organization and evolution of amniote sex chromosomes, and hypothesize that dosage insensitivity might predispose an autosome to evolving function as a sex chromosome.     

The multiple sex chromosomes of platypus and echidna are not completely identical and several share homology with the avian Z

Background

Sex-determining systems have evolved independently in vertebrates. Placental mammals and marsupials have an XY system, birds have a ZW system. Reptiles and amphibians have different systems, including temperature-dependent sex determination, and XY and ZW systems that differ in origin from birds and placental mammals. Monotremes diverged early in mammalian evolution, just after the mammalian clade diverged from the sauropsid clade. Our previous studies showed that male platypus has five X and five Y chromosomes, no SRY, and DMRT1 on an X chromosome. In order to investigate monotreme sex chromosome evolution, we performed a comparative study of platypus and echidna by chromosome painting and comparative gene mapping.

Results

Chromosome painting reveals a meiotic chain of nine sex chromosomes in the male echidna and establishes their order in the chain. Two of those differ from those in the platypus, three of the platypus sex chromosomes differ from those of the echidna and the order of several chromosomes is rearranged. Comparative gene mapping shows that, in addition to bird autosome regions, regions of bird Z chromosomes are homologous to regions in four platypus X chromosomes, that is, X₁, X₂, X₃, X₅, and in chromosome Y₁.

Conclusion

Monotreme sex chromosomes are easiest to explain on the hypothesis that autosomes were added sequentially to the translocation chain, with the final additions after platypus and echidna divergence. Genome sequencing and contig anchoring show no homology yet between platypus and therian Xs; thus, monotremes have a unique XY sex chromosome system that shares some homology with the avian Z.     

Conserved synteny between the chicken Z sex chromosome and human chromosome 9 includes the male regulatory gene DMRT1: a comparative (re)view on avian sex determination

Sex-determination mechanisms in birds and mammals evolved independently for more than 300 million years. Unlike mammals, sex determination in birds operates through a ZZ/ZW sex chromosome system, in which the female is the heterogametic sex. However, the molecular mechanism remains to be elucidated. Comparative gene mapping revealed that several genes on human chromosome 9 (HSA 9) have homologs on the chicken Z chromosome (GGA Z), indicating the common ancestry of large parts of GGA Z and HSA 9. Based on chromosome homology maps, we isolated a Z-linked chicken ortholog of DMRT1, which has been implicated in XY sex reversal in humans. Its location on the avian Z and within the sex-reversal region on HSA 9p suggests that DMRT1 represents an ancestral dosage-sensitive gene for vertebrate sex-determination. Z dosage may be crucial for male sexual differentiation/determination in birds.     

Mammalian sex--Origin and evolution of the Y chromosome and SRY

Sex determination in vertebrates is accomplished through a highly conserved genetic pathway. But surprisingly, the downstream events may be activated by a variety of triggers, including sex determining genes and environmental cues. Amongst species with genetic sex determination, the sex determining gene is anything but conserved, and the chromosomes that bear this master switch subscribe to special rules of evolution and function. In mammals, with a few notable exceptions, female are homogametic (XX) and males have a single X and a small, heterochromatic and gene poor Y that bears a male dominant sex determining gene SRY. The bird sex chromosome system is the converse in that females are the heterogametic sex (ZW) and males the homogametic sex (ZZ). There is no SRY in birds, and the dosage-sensitive Z-borne DMRT1 gene is a credible candidate sex determining gene. Different sex determining switches seem therefore to have evolved independently in different lineages, although the complex sex chromosomes of the platypus offer us tantalizing clues that the mammal XY system may have evolved directly from an ancient reptile ZW system. In this review we will discuss the organization and evolution of the sex chromosomes across a broad range of mammals, and speculate on how the Y chromosome, and SRY, evolved.     

Sexually antagonistic chromosomal cuckoos

The two kinds of sex chromosomes in the heterogametic parent are transmitted to offspring with different sexes, causing opposite-sex siblings to be completely unrelated for genes located on these chromosomes. Just as the nest-parasitic cuckoo chick is selected to harm its unrelated nest-mates in order to garner more shared resources, sibling competition causes the sex chromosomes to be selected to harm siblings that do not carry them. Here we quantify and contrast this selection on the X and Y, or Z and W, sex chromosomes. We also develop a hypothesis for how this selection can contribute to the decay of the non-recombining sex chromosome.     

A new look at the evolution of avian sex chromosomes

Birds have a ubiquitous, female heterogametic, ZW sex chromosome system. The current model suggests that the Z chromosome and its degraded partner, the W chromosome, evolved from an ancestral pair of autosomes independently from the mammalian XY male heteromorphic sex chromosomes--which are similar in size, but not gene content (Graves, 1995; Fridolfsson et al., 1998). Furthermore the degradation of the W has been proposed to be progressive, with the basal clade of birds (the ratites) possessing virtually homomorphic sex chromosomes and the more recently derived birds (the carinates) possessing highly heteromorphic sex chromosomes (Ohno, 1967; Solari, 1993). Recent findings have suggested an alternative to independent evolution of bird and mammal chromosomes, in which an XY system took over directly from an ancestral ZW system. Here we examine recent research into avian sex chromosomes and offer alternative suggestions as to their evolution.     

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.     

Meiotic drive and sex chromosome cycling

Sex-linked meiotic drive is found in a broad variety of taxa, including insects, birds, and mammals. In populations of some species, we see four types of sex chromosomes segregating: normal and driving X chromosomes and susceptible and resistant Y chromosomes. A theoretical analysis shows that a stable four-chromosome equilibria is a more common outcome in these systems than previously recognized. Cycling of sex chromosome frequencies and associated changes in the sex ratio are other predicted outcomes. The absence of cycling in nature may be due to migration among populations.