In mammals, meiosis is initiated at different time points in males and females, but the mechanism underlying this difference is unknown. Female germ cells begin meiosis during embryogenesis. In males, embryonic germ cells undergo G₀/G₁mitotic cell cycle arrest, and meiosis begins after birth. In mice, theStimulated by Retinoic Acid Gene 8(Stra8) has been found to be required for the transition into meiosis in both female and male germ cells.Stra8is expressed in embryonic ovaries just before meiotic initiation, whereas its expression in testes is first detected after birth. Here we examine the mechanism underlying the sex-specific timing ofStra8expression and meiotic initiation in mice. Our work shows that signaling by retinoic acid (RA), an active derivative of vitamin A, is required forStra8expression and thereby meiotic initiation in embryonic ovaries. We also discovered that RA is sufficient to induceStra8expression in embryonic testes and in vitamin A-deficient adult testesin vivo. Finally, our results show that cytochrome p450 (CYP)-mediated RA metabolism prevents prematureStra8expression in embryonic testes. Treatment with an inhibitor specific to RA-metabolizing enzymes indicates that a cytochrome p450 from the 26 family (CYP26) is responsible for delayingStra8expression in embryonic testes. Sex-specific regulation of RA signaling thus plays an essential role in meiotic initiation in embryonic ovaries and precludes its occurrence in embryonic testes. Because RA signaling regulatesStra8expression in both embryonic ovaries and adult testes, this portion of the meiotic initiation pathway may be identical in both sexes.

In eukaryotes, diploid cells give rise to haploid cells via meiosis, a program of two cell divisions preceded by one round of DNA replication. Although key molecular components of the meiotic apparatus are highly conserved among eukaryotes, the mechanisms responsible for initiating the meiotic program have diverged substantially among eukaryotes. This raises a related question in animals with two distinct sexes: Within a given species, are similar or different mechanisms of meiotic initiation used in the male and female germ lines? In mammals, this question is underscored by dramatic differences in the timing of meiotic initiation in males and females. Stra8 is a vertebrate-specific, cytoplasmic factor expressed by germ cells in response to retinoic acid. We previously demonstrated that Stra8 gene function is required for meiotic initiation in mouse embryonic ovaries. Here we report that, on an inbred C57BL/6 genetic background, the same factor is also required for meiotic initiation in germ cells of juvenile mouse testes. In juvenile C57BL/6 males lacking Stra8 gene function, the early mitotic development of germ cells appears to be undisturbed. However, these cells then fail to undergo the morphological changes that define meiotic prophase, and they do not display the molecular hallmarks of meiotic chromosome cohesion, synapsis and recombination. We conclude that, in mice, Stra8 regulates meiotic initiation in both spermatogenesis and oogenesis. Taken together with previous observations, our present findings indicate that, in both the male and female germ lines, meiosis is initiated through retinoic acid induction of Stra8 .

With the sequencing of the male-specific region of the chimpanzee Y chromosome, it is now possible to make comparisons with the human Y sequence and to learn more about the recent evolution of the human Y chromosome. The two sequences differ markedly in structure and gene content, indicating rapid evolution during the past 6 million years. This finding is at odds with the common view that Y chromosomes are essentially static structures that evolve only very slowly by genetic loss. Rather, renovation and remodelling dominate the evolution of human and chimpanzee Y chromosomes. Possible reasons for this extraordinary divergence include genetic hitchhiking effects, species-specific mating behaviours and the Y chromosome's role in sperm production. Little is known about the recent evolution of the Y chromosome because only the human Y chromosome has been fully sequenced. The sequencing of the male-specific region of the Y chromosome (MSY) in the chimpanzee and comparison between the MSYs of the two species now reveals that they differ radically in sequence structure and gene content, indicating rapid evolution over the past 6 million years. The human Y chromosome began to evolve from an autosome hundreds of millions of years ago, acquiring a sex-determining function and undergoing a series of inversions that suppressed crossing over with the X chromosome1,2. Little is known about the recent evolution of the Y chromosome because only the human Y chromosome has been fully sequenced. Prevailing theories hold that Y chromosomes evolve by gene loss, the pace of which slows over time, eventually leading to a paucity of genes, and stasis3,4. These theories have been buttressed by partial sequence data from newly emergent plant and animal Y chromosomes5,6,7,8, but they have not been tested in older, highly evolved Y chromosomes such as that of humans. Here we finished sequencing of the male-specific region of the Y chromosome (MSY) in our closest living relative, the chimpanzee, achieving levels of accuracy and completion previously reached for the human MSY. By comparing the MSYs of the two species we show that they differ radically in sequence structure and gene content, indicating rapid evolution during the past 6 million years. The chimpanzee MSY contains twice as many massive palindromes as the human MSY, yet it has lost large fractions of the MSY protein-coding genes and gene families present in the last common ancestor. We suggest that the extraordinary divergence of the chimpanzee and human MSYs was driven by four synergistic factors: the prominent role of the MSY in sperm production, ‘genetic hitchhiking’ effects in the absence of meiotic crossing over, frequent ectopic recombination within the MSY, and species differences in mating behaviour. Although genetic decay may be the principal dynamic in the evolution of newly emergent Y chromosomes, wholesale renovation is the paramount theme in the continuing evolution of chimpanzee, human and perhaps other older MSYs.

Birds and mammals have distinct sex chromosomes. In birds, males have a pair of Z chromosomes and females a Z and a W. In mammals, males are XY and females XX. It has long been assumed that sex-chromosome evolution has involved dramatic modification of the sex-specific (W and Y) chromosomes but only modest changes to the Z and X chromosomes shared by the sexes. Not so, according to a new study reporting the sequence of the chicken Z chromosome and comparing it with the finished sequence of human X. The Z and X chromosomes have changed dramatically from the autosomal (non-sex) chromosomes that gave rise to them. And they seem to have followed convergent evolutionary trajectories, including the acquisition and amplification of testis-expressed gene families, despite having arisen independently from different portions of the ancestral genome. Birds and mammals have distinct sex chromosomes: in birds, males are ZZ and females ZW; in mammals, males are XY and females XX. By sequencing the chicken Z chromosome and comparing it with the human X chromosome, these authors overturn the currently held view that these chromosomes have diverged little from their autosomal progenitors. The Z and X chromosomes seem to have followed convergent evolutionary trajectories, despite evolving with opposite systems of heterogamety. In birds, as in mammals, one pair of chromosomes differs between the sexes. In birds, males are ZZ and females ZW. In mammals, males are XY and females XX. Like the mammalian XY pair, the avian ZW pair is believed to have evolved from autosomes, with most change occurring in the chromosomes found in only one sex—the W and Y chromosomes1,2,3,4,5. By contrast, the sex chromosomes found in both sexes—the Z and X chromosomes—are assumed to have diverged little from their autosomal progenitors2. Here we report findings that challenge this assumption for both the chicken Z chromosome and the human X chromosome. The chicken Z chromosome, which we sequenced essentially to completion, is less gene-dense than chicken autosomes but contains a massive tandem array containing hundreds of duplicated genes expressed in testes. A comprehensive comparison of the chicken Z chromosome with the finished sequence of the human X chromosome demonstrates that each evolved independently from different portions of the ancestral genome. Despite this independence, the chicken Z and human X chromosomes share features that distinguish them from autosomes: the acquisition and amplification of testis-expressed genes, and a low gene density resulting from an expansion of intergenic regions. These features were not present on the autosomes from which the Z and X chromosomes originated but were instead acquired during the evolution of Z and X as sex chromosomes. We conclude that the avian Z and mammalian X chromosomes followed convergent evolutionary trajectories, despite their evolving with opposite (female versus male) systems of heterogamety. More broadly, in birds and mammals, sex chromosome evolution involved not only gene loss in sex-specific chromosomes, but also marked expansion and gene acquisition in sex chromosomes common to males and females.

The genetics of sexual dimorphism: In mammals, many species exhibit sex-specific phenotypes that differ between males and females. Although attention has been directed to the effects of the X and Y sex chromosomes, we do not understand how sex affects the rest of the genome. Naqvi et al. examined gene expression in 12 tissues in male and female humans, mice, rats, dogs, and cynomolgus macaques and identified diversity in gene expression between the sexes. Examining sex-biased gene expression in human height identified opposing male or female bias. Although conservation of differential sex-specific gene expression among species was observed, specific genes differed in the sexes among species and lineages suggesting the evolution of species- or lineage-specific sex-biased expression. Science , this issue p. eaaw7317