Complex history and differentiation patterns of the t-haplotype, a mouse meiotic driver

The t-haplotype, a mouse meiotic driver found on chromosome 17, has been a model for autosomal segregation distortion for close to a century, but several questions remain regarding its biology and evolutionary history. A recently published set of population genomics resources for wild mice includes several individuals heterozygous for the t-haplotype, which we use to characterize this selfish element at the genomic and transcriptomic level. Our results show that large sections of the t-haplotype have been replaced by standard homologous sequences, possibly due to occasional events of recombination, and that this complicates the inference of its history. As expected for a long genomic segment of very low recombination, the t-haplotype carries an excess of fixed nonsynonymous mutations compared to the standard chromosome. This excess is stronger for regions that have not undergone recent recombination, suggesting that occasional gene flow between the t and the standard chromosome may provide a mechanism to regenerate coding sequences that have accumulated deleterious mutations. Finally, we find that t-complex genes with altered expression largely overlap with deleted or amplified regions, and that carrying a t-haplotype alters the testis expression of genes outside of the t-complex, providing new leads into the pathways involved in the biology of this segregation distorter

X chromosome evolution in Drosophila

Although the X chromosome is usually similar to the autosomes in size, gene density 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. In this thesis, I have attempted to investigate some of these patterns and their possible causes. The first two chapters consist of theoretical and empirical work intended to analyse the rates of evolution of coding sequences of X-linked and autosomal loci, with particular emphasis on faster-X evolution, the theory that more effective selection on the X can lead to higher rates of adaptive evolution on this chromosome. By analyzing X-linked and autosomal coding sequence in several species of Drosophila, we found some evidence for more effective selection on the X, particularly evident in the higher levels of codon usage bias detected at X-linked loci. We argue that this could be due to higher levels of recombination on the X chromosome increasing its effective population size (NeX) relative to the autosomal effective population size (NeA). To further investigate this hypothesis, we have modeled the effect of increased NeX/NeA on rates of evolution and confirmed that this can contribute to faster-X evolution. The last two chapters deal with the evolution of sex-biased genes and the possible causes for their differential accumulation on the X. We used EST data to create expression profiles for D. melanogaster male-, female- and unbiased genes. Our results suggest that the expression levels of sex-biased genes are incompatible with the accepted iii model of sex-biased gene evolution. We also show that the deficit of testis-expressed genes that is observed in Drosophila seems to be stronger for highly expressed genes. In fact, for very lowly expressed genes, we observe a small excess of testis-expressed genes on the X. We attempt to discuss this pattern in view of what is currently known about the evolution of sex-biased gene expression

The deep conservation of the Lepidoptera Z chromosome suggests a non canonical origin of the W

Moths and butterflies (Lepidoptera) usually have a pair of differentiated WZ sex chromosomes. However, in most lineages outside of the division Ditrysia, as well as in the sister order Trichoptera, females lack a W chromosome. The W is therefore thought to have been acquired secondarily. Here we compare the genomes of three Lepidoptera species (one Dytrisia and two non-Dytrisia) to test three models accounting for the origin of the W: (1) a Z-autosome fusion; (2) a sex chromosome turnover; and (3) a non-canonical mechanism (e.g., through the recruitment of a B chromosome). We show that the gene content of the Z is highly conserved across Lepidoptera (rejecting a sex chromosome turnover) and that very few genes moved onto the Z in the common ancestor of the Ditrysia (arguing against a Z-autosome fusion). Our comparative genomics analysis therefore supports the secondary acquisition of the Lepidoptera W by a non-canonical mechanism, and it confirms the extreme stability of well-differentiated sex chromosomes

Global dosage compensation is ubiquitous in Lepidoptera, but counteracted by the masculinization of the Z chromosome

While chromosome-wide dosage compensation of the X chromosome has been found in many species, studies in ZW clades have indicated that compensation of the Z is more localized and/or incomplete. In the ZW Lepidoptera, some species show complete compensation of the Z chromosome, while others lack full equalization, but what drives these inconsistencies is unclear. Here, we compare patterns of male and female gene expression on the Z chromosome of two closely related butterfly species, Papilio xuthus and Papilio machaon, and in multiple tissues of two moths species, Plodia interpunctella and Bombyx mori, which were previously found to differ in the extent to which they equalize Z-linked gene expression between the sexes. We find that, while some species and tissues seem to have incomplete dosage compensation, this is in fact due to the accumulation of male-biased genes and the depletion of female-biased genes on the Z chromosome. Once this is accounted for, the Z chromosome is fully compensated in all four species, through the up-regulation of Z expression in females and in some cases additional down-regulation in males. We further find that both sex-biased genes and Z-linked genes have increased rates of expression divergence in this clade, and that this can lead to fast shifts in patterns of gene expression even between closely related species. Taken together, these results show that the uneven distribution of sex-biased genes on sex chromosomes can confound conclusions about dosage compensation and that Z chromosome-wide dosage compensation is not only possible but ubiquitous among Lepidoptera

The X chromosome of insects likely predates the origin of Class Insecta

Sex chromosomes have evolved independently multiple times, but why some are conserved for more than 100 million years whereas others turnover rapidly remains an open question. Here, we examine the homology of sex chromosomes across nine orders of insects, plus the outgroup springtails. We find that the X chromosome is likely homologous across insects and springtails; the only exception is in the Lepidoptera, which has lost the X and now has a ZZ/ZW sex chromosome system. These results suggest the ancestral insect X chromosome has persisted for more than 450 million years – the oldest known sex chromosome to date. Further, we propose that the shrinking of gene content the dipteran X chromosome has allowed for a burst of sex-chromosome turnover that is absent from other speciose insect orders

Diversity of modes of reproduction and sex determination systems in invertebrates, and the putative contribution of genetic conflict

About eight million animal species are estimated to live on Earth, and all except those belonging to one subphylum are invertebrates. Invertebrates are incredibly diverse in their morphologies, life histories, and in the range of the ecological niches that they occupy. A great variety of modes of reproduction and sex determination systems is also observed among them, and their mosaic-distribution across the phylogeny shows that transitions between them occur frequently and rapidly. Genetic conflict in its various forms is a long-standing theory to explain what drives those evolutionary transitions. Here, we review (1) the different modes of reproduction among invertebrate species, highlighting sexual reproduction as the probable ancestral state; (2) the paradoxical diversity of sex determination systems; (3) the different types of genetic conflicts that could drive the evolution of such different systems

Novel patterns of expression and recruitment of new genes on the t-haplotype, a mouse selfish chromosome

The t-haplotype of mice is a classical model for autosomal transmission distortion. A largely non-recombining variant of the proximal region of chromosome 17, it is transmitted to more than 90% of the progeny of heterozygous males through the disabling of sperm carrying a standard chromosome. While extensive genetic and functional work has shed light on individual genes involved in drive, much less is known about the evolution and function of the rest of its hundreds of genes. Here, we characterize the sequence and expression of dozens of t-specific transcripts and of their chromosome 17 homologues. Many genes showed reduced expression of the t-allele, but an equal number of genes showed increased expression of their t-copy, consistent with increased activity or a newly evolved function. Genes on the t-haplotype had a significantly higher non-synonymous substitution rate than their homologues on the standard chromosome, with several genes harbouring dN/dS ratios above 1. Finally, the t-haplotype has acquired at least two genes from other chromosomes, which show high and tissue-specific expression. These results provide a first overview of the gene content of this selfish element, and support a more dynamic evolutionary scenario than expected of a large genomic region with almost no recombination

Novel patterns of expression and recruitment of new genes on the t-haplotype, a mouse selfish chromosome

The t-haplotype of mice is a classical model for autosomal transmission distortion. A largely non-recombining variant of the proximal region of chromosome 17, it is transmitted to more than 90% of the progeny of heterozygous males through the disabling of sperm carrying a standard chromosome. While extensive genetic and functional work has shed light on individual genes involved in drive, much less is known about the evolution and function of the rest of its hundreds of genes. Here, we characterize the sequence and expression of dozens of t-specific transcripts and of their chromosome 17 homologues. Many genes showed reduced expression of the t-allele, but an equal number of genes showed increased expression of their t-copy, consistent with increased activity or a newly evolved function. Genes on the t-haplotype had a significantly higher non-synonymous substitution rate than their homologues on the standard chromosome, with several genes harbouring dN/dS ratios above 1. Finally, the t-haplotype has acquired at least two genes from other chromosomes, which show high and tissue-specific expression. These results provide a first overview of the gene content of this selfish element, and support a more dynamic evolutionary scenario than expected of a large genomic region with almost no recombination

Schistosome W-Linked genes inform temporal dynamics of sex chromosome evolution and suggest candidate for sex determination

Schistosomes, the human parasites responsible for snail fever, are female-heterogametic. Different parts of their ZW sex chromosomes have stopped recombining in distinct lineages, creating “evolutionary strata” of various ages. Although the Z-chromosome is well characterized at the genomic and molecular level, the W-chromosome has remained largely unstudied from an evolutionary perspective, as only a few W-linked genes have been detected outside of the model species Schistosoma mansoni. Here, we characterize the gene content and evolution of the W-chromosomes of S. mansoni and of the divergent species S. japonicum. We use a combined RNA/DNA k-mer based pipeline to assemble around 100 candidate W-specific transcripts in each of the species. About half of them map to known protein coding genes, the majority homologous to S. mansoni Z-linked genes. We perform an extended analysis of the evolutionary strata present in the two species (including characterizing a previously undetected young stratum in S. japonicum) to infer patterns of sequence and expression evolution of W-linked genes at different time points after recombination was lost. W-linked genes show evidence of degeneration, including high rates of protein evolution and reduced expression. Most are found in young lineage-specific strata, with only a few high expression ancestral W-genes remaining, consistent with the progressive erosion of nonrecombining regions. Among these, the splicing factor u2af2 stands out as a promising candidate for primary sex determination, opening new avenues for understanding the molecular basis of the reproductive biology of this group

Sex-biased gene expression and dosage compensation on the Artemia franciscana Z-chromosome

Males and females of Artemia franciscana, a crustacean commonly used in the aquarium trade, are highly dimorphic. Sex is determined by a pair of ZW chromosomes, but the nature and extent of differentiation of these chromosomes is unknown. Here, we characterize the Z chromosome by detecting genomic regions that show lower genomic coverage in female than in male samples, and regions that harbor an excess of female-specific SNPs. We detect many Z-specific genes, which no longer have homologs on the W, but also Z-linked genes that appear to have diverged very recently from their existing W-linked homolog. We assess patterns of male and female expression in two tissues with extensive morphological dimorphism, gonads, and heads. In agreement with their morphology, sex-biased expression is common in both tissues. Interestingly, the Z chromosome is not enriched for sex-biased genes, and seems to in fact have a mechanism of dosage compensation that leads to equal expression in males and in females. Both of these patterns are contrary to most ZW systems studied so far, making A. franciscana an excellent model for investigating the interplay between the evolution of sexual dimorphism and dosage compensation, as well as Z chromosome evolution in general