Beatriz Vicoso

Evolution on the X chromosome: unusual patterns and processes

Although the X chromosome is usually similar to the autosomes in size and cytogenetic appearance, theoretical models predict that its hemizygosity in males may cause unusual patterns of evolution. The sequencing of several genomes has indeed revealed differences between the X chromosome and the autosomes in the rates of gene divergence, patterns of gene expression and rates of gene movement between chromosomes. A better understanding of these patterns should provide valuable information on the evolution of genes located on the X chromosome. It could also suggest solutions to more general problems in molecular evolution, such as detecting selection and estimating mutational effects on fitness.

Comparative Sex Chromosome Genomics in Snakes: Differentiation, Evolutionary Strata, and Lack of Global Dosage Compensation

Analysis of the genomes and transcriptomes of snake species with homomorphic and heteromorphic sex chromosomes reveals the evolutionary dynamics of sex chromosome differentiation.

EFFECTIVE POPULATION SIZE AND THE FASTER-X EFFECT: EMPIRICAL RESULTS AND THEIR INTERPRETATION

The X or Z chromosome has several characteristics that distinguish it from the autosomes, namely hemizygosity in the heterogametic sex, and a potentially different effective population size, both of which may influence the rate and nature of evolution. In particular, there may be an accelerated rate of adaptive change for X‐linked compared to autosomal coding sequences, often referred to as the Faster‐X effect. Empirical studies have indicated that the strength of Faster‐X evolution varies among different species, and theoretical treatments have shown that demography and mating system can substantially affect the degree of Faster‐X evolution. Here we integrate genomic data on Faster‐X evolution from a variety of animals with the demographic factors, mating system, and sex chromosome regulatory characteristics that may influence it. Our results suggest that differences in effective population size and mechanisms of dosage compensation may influence the perceived extent of Faster‐X evolution, and help to explain several clade‐specific patterns that we observe.

EFFECTIVE POPULATION SIZE AND THE FASTER-X EFFECT: AN EXTENDED MODEL

Current models of X-linked and autosomal evolutionary rates often assume that the effective population size of the X chromosome (NeX ) is equal to three-quarters of the autosomal population size (NeA). However, polymorphism studies of Drosophila melanogaster and D. simulans suggest that there are often significant deviations from this value. We have computed fixation rates of beneficial and deleterious mutations at X-linked and autosomal sites when this occurs. We find that NeX/NeA is a crucial parameter for the rates of evolution of X-linked sites compared to autosomal sites. Faster-X evolution due to the fixation of beneficial mutations can occur under a much wider range of levels of dominance when NeX/NeA > ¾. We also examined various parameters that are known to influence the rates of evolution at X-linked and autosomal sites, such as different mutation rates in males and females and mutations that are sexually antagonistic, to determine which cases can lead to faster-X evolution. We show that, when the rate of nonsynonymous evolution is normalized by the rate of neutral evolution, a sex difference in mutation rate has no influence on the conditions for faster-X evolution.

Numerous Transitions of Sex Chromosomes in Diptera

Many species groups, including mammals and many insects, determine sex using heteromorphic sex chromosomes. Diptera flies, which include the model Drosophila melanogaster, generally have XY sex chromosomes and a conserved karyotype consisting of six chromosomal arms (five large rods and a small dot), but superficially similar karyotypes may conceal the true extent of sex chromosome variation. Here, we use whole-genome analysis in 37 fly species belonging to 22 different families of Diptera and uncover tremendous hidden diversity in sex chromosome karyotypes among flies. We identify over a dozen different sex chromosome configurations, and the small dot chromosome is repeatedly used as the sex chromosome, which presumably reflects the ancestral karyotype of higher Diptera. However, we identify species with undifferentiated sex chromosomes, others in which a different chromosome replaced the dot as a sex chromosome or in which up to three chromosomal elements became incorporated into the sex chromosomes, and others yet with female heterogamety (ZW sex chromosomes). Transcriptome analysis shows that dosage compensation has evolved multiple times in flies, consistently through up-regulation of the single X in males. However, X chromosomes generally show a deficiency of genes with male-biased expression, possibly reflecting sex-specific selective pressures. These species thus provide a rich resource to study sex chromosome biology in a comparative manner and show that similar selective forces have shaped the unique evolution of sex chromosomes in diverse fly taxa.

Reversal of an ancient sex chromosome to an autosome in Drosophila

Although transitions of sex-determination mechanisms are frequent in species with homomorphic sex chromosomes, heteromorphic sex chromosomes are thought to represent a terminal evolutionary stage owing to chromosome-specific adaptations such as dosage compensation or an accumulation of sex-specific mutations. Here we show that an autosome of Drosophila, the dot chromosome, was ancestrally a differentiated X chromosome. We analyse the whole genome of true fruitflies (Tephritidae), flesh flies (Sarcophagidae) and soldier flies (Stratiomyidae) to show that genes located on the dot chromosome of Drosophila are X-linked in outgroup species, whereas Drosophila X-linked genes are autosomal. We date this chromosomal transition to early drosophilid evolution by sequencing the genome of other Drosophilidae. Our results reveal several puzzling aspects of Drosophila dot chromosome biology to be possible remnants of its former life as a sex chromosome, such as its minor feminizing role in sex determination or its targeting by a chromosome-specific regulatory mechanism. We also show that patterns of biased gene expression of the dot chromosome during early embryogenesis, oogenesis and spermatogenesis resemble that of the current X chromosome. Thus, although sex chromosomes are not necessarily evolutionary end points and can revert back to an autosomal inheritance, the highly specialized genome architecture of this former X chromosome suggests that severe fitness costs must be overcome for such a turnover to occur.

Sex-biased gene expression at homomorphic sex chromosomes in emus and its implication for sex chromosome evolution

Sex chromosomes originate from autosomes. The accumulation of sexually antagonistic mutations on protosex chromosomes selects for a loss of recombination and sets in motion the evolutionary processes generating heteromorphic sex chromosomes. Recombination suppression and differentiation are generally viewed as the default path of sex chromosome evolution, and the occurrence of old, homomorphic sex chromosomes, such as those of ratite birds, has remained a mystery. Here, we analyze the genome and transcriptome of emu (Dromaius novaehollandiae) and confirm that most genes on the sex chromosome are shared between the Z and W. Surprisingly, however, levels of gene expression are generally sex-biased for all sex-linked genes relative to autosomes, including those in the pseudoautosomal region, and the male-bias increases after gonad formation. This expression bias suggests that the emu sex chromosomes have become masculinized, even in the absence of ZW differentiation. Thus, birds may have taken different evolutionary solutions to minimize the deleterious effects imposed by sexually antagonistic mutations: some lineages eliminate recombination along the protosex chromosomes to physically restrict sexually antagonistic alleles to one sex, whereas ratites evolved sex-biased expression to confine the product of a sexually antagonistic allele to the sex it benefits. This difference in conflict resolution may explain the preservation of recombining, homomorphic sex chromosomes in other lineages and illustrates the importance of sexually antagonistic mutations driving the evolution of sex chromosomes.

The deficit of male-biased genes on the D. melanogaster X chromosome is expression-dependent: a consequence of dosage compensation?

In Drosophila, there is a consistent deficit of male-biased genes on the X chromosome. It has been suggested that male-biased genes may evolve from initially unbiased genes as a result of increased expression levels in males. If transcription rates are limited, a large increase in expression in the testis may be harder to achieve for single-copy X-linked genes than for autosomal genes, because they are already hypertranscribed due to dosage compensation. This hypothesis predicts that the larger the increase in expression required to make a male-biased gene, the lower the chance of this being achievable if it is located on the X chromosome. Consequently, highly expressed male-biased genes should be located on the X chromosome less often than lowly expressed male-biased genes. This pattern is observed in our analysis of publicly available data, where microarray data or EST data are used to detect male-biased genes in D. melanogaster and to measure their expression levels. This is consistent with the idea that limitations in transcription rates may prevent male-biased genes from accumulating on the X chromosome.

Progress and prospects toward our understanding of the evolution of dosage compensation

In many eukaryotic organisms, gender is determined by a pair of heteromorphic sex chromosomes. Degeneration of the non-recombining Y chromosome is a general facet of sex chromosome evolution. Selective pressure to restore expression levels of X-linked genes relative to autosomes accompanies Y-chromosome degeneration, thus driving the evolution of dosage compensation mechanisms. This review focuses on evolutionary aspects of dosage compensation, in light of recent advances in comparative and functional genomics that have substantially increased our understanding of the molecular mechanisms of dosage compensation and how it evolved. We review processes involved in sex chromosome evolution, and discuss the dynamic interaction between Y degeneration and the acquisition of dosage compensation. We compare mechanisms of dosage compensation and the origin of dosage compensation genes between different taxa and comment on sex chromosomes that apparently lack compensation mechanisms. Finally, we discuss how dosage compensation systems can also influence the evolution of well-established sex chromosomes.

Lack of global dosage compensation in Schistosoma mansoni, a female-heterogametic parasite

Many species have morphologically and genetically differentiated sex chromosomes, such as the XY pair of mammals. Y chromosomes are often highly degenerated and carry few functional genes, so that XY males have only one copy of most X-linked genes (whereas females have two). As a result, chromosome-wide mechanisms of dosage compensation, such as the mammalian X-inactivation, often evolve to reestablish expression balance. A similar phenomenon is expected in female-heterogametic species, where ZW females should suffer from imbalances due to W-chromosome degeneration. However, no global dosage compensation mechanisms have been detected in the two independent ZW systems that have been studied systematically (birds and silkworm), leading to the suggestion that lack of global dosage compensation may be a general feature of female-heterogametic species. However, analyses of other independently evolved ZW systems are required to test if this is the case. In this study, we use published genomic and expression data to test for the presence of global dosage compensation in Schistosoma mansoni, a trematode parasite that causes schistosomiasis in humans. We find that Z-linked expression is reduced relative to autosomal expression in females but not males, consistent with incomplete or localized dosage compensation. This gives further support to the theory that female-heterogametic species may not require global mechanisms of dosage compensation.