the causes of Y chromosome degeneration • the evolution of gene expression and dosage compensation • heterochromatin formation • gene trafficking off X chromosomes • evolution of gene expression in ZW systems • speciation in drosophila • evolution of chromatin structure • mammals with clonal chromosomes

     The main research interest of our lab is in the evolutionary significance of sex and recombination, the mode and tempo of genome evolution, the genomics of speciation, and the evolution of epigenetic modifications. Questions of interest to us include: Why is recombination so prevalent in eukaryotes? Why do non-recombining parts of the genome in sexual species, like the Y chromosome, degenerate? How do patterns of genome evolution and genome-wide expression-levels respond to changes in genome architecture and recombination rate? How does dosage compensation evolve? How do epigenetic modifications, such as the formation of heterochromatin or hypertranscribed chromatin, evolve? Why do genes with sex-biased expression show a non-random distribution across the genome? How do new species form?
     Most of our work involves using
Drosophila as a model but more recently, our lab has also started to explore species where females are the heterogametic sex, such as birds and snakes. We use several different approaches in our research, combining molecular and computational genomics techniques, comparative and functional genomics approaches, theoretical modeling and experimental tests. Current research focuses on the following areas:

The tree of sex.

     Sex is universal among living organisms, yet a mind-boggling diversity of mechanisms that determine the sex of an individual exists. These include chromosomal sex determination (such as in humans, where males have an X and a Y chromosome, and females have two X chromosomes), environmental sex determination (such as in many reptiles, where environmental cues – such as temperature – determine sex), or haplo-diploid sex determination (where fertilized eggs develop as females, and unfertilized eggs develop as males – such as in bees), amongst others. While some taxonomic groups (such as mammals and birds) have stable sex determination mechanisms, in other taxa (such as insects and fish), sex determination mechanisms can vary greatly among closely related species, or even among individuals within a species. This variation is surprising, given that sex determination is a fundamental biological process. The evolutionary forces that drive this variation of sex determination systems are not understood. The “
Tree of Sex Consortium” has assembled a database which is listing sexual systems and sex determination mechanisms across the eukaryotic tree of life.

The causes of Y chromosome degeneration.

     It is generally believed that the advantage of sex lies in the associated process of genetic recombination during meiosis, which constitutes the main difference between sexual and asexual reproduction. Asexual species of eukaryotes seem to go extinct at a higher rate than their sexual relatives. Likewise, non-recombining parts of the genome in sexual species are prone to degeneration: X and Y chromosomes are derived from a pair of ordinary autosomes, and the lack of recombination on the Y chromosome has resulted in its degeneration. The non-recombining portion of Y chromosomes is characterized by a paucity of active genes and an abundance of repetitive sequences. We are using comparative genomics approaches, population genetics and molecular genetic approaches to study the forces responsible for Y chromosome degeneration in
Drosophila, using three model species: D. miranda, D. albomicans and D. athabasca. These species all have Y chromosomes that were formed very recently on an evolutionary time scale, allowing us to study the process of Y chromosome degeneration in action.

The evolution of gene expression and dosage compensation.
     The degeneration of the Y chromosome creates the problem of reduced gene-dosage of X-linked genes in males, resulting in the evolution of dosage-compensation mechanisms. Dramatically different dosage-compensation mechanisms have evolved in different organisms: Mammals inactivate one of their two X chromosomes in females, XX hermaphrodite C. elegans effectively halve the expression from each X, and male Drosophila increase the transcription of their single X approximately twofold. Large parts of the neo-Y chromosome in D. miranda show various signs of degeneration, and some parts of the neo-X already recruit the molecular machinery necessary for dosage compensation. Using a library of tools from comparative genomics, population genetics to gene expression studies, we investigate how gene expression patterns evolve on these newly formed sex chromosomes, and, in particular, the evolution of dosage compensation.

The formation of heterochromatin on evolving Y chromosomes.
Significant portions of eukaryotic genomes, including the Y chromosome, are heterochromatic, made up largely of repetitive sequences and possessing a distinctive chromatin structure associated with gene silencing. Heterochromatic regions have a high repeat content and are characterized by specific histone modifications, but the primary sequence elements that define specific chromosomal domains as preferred sites of heterochromatin assembly are not well understood. Recent studies suggest that small RNAs, possibly derived from transposable elements, contribute to heterochromatin targeting. The recently formed neo-Y chromosomes of
Drosophila albomicans and D. miranda are in the process of evolving altered chromatin structure and provide unique systems to study the mechanisms and evolution of heterochromatin formation in action using a comparative and functional genomics approach.

Speciation in
     The biological species concept defines species in terms of groups of interbreeding individuals. Most speciation models require restricted gene flow between populations, allowing them to diverge genetically and morphologically. However, many of these models also allow a period of secondary contact, where natural selection can act to complete the speciation process. During this period of incipient speciation, reproductive isolation between closely related species is not complete and hybrids can form. If hybrids are viable and fertile, gene flow between such diverging species can occur, and the hybridization will introduce sets of foreign alleles. Genomic regions that did not diverge functionally between species may be readily introgressed, while genes or genomic regions that are well adapted in one species but not the other will tend to be eliminated by natural selection. We are studying two species groups in
Drosophila (the D. nasuta - D. albomicans species complex and the D. athabasca species complex), in order to identify genomic regions involved in species-specific adaptations and species formation.

Gene expression in ZW systems
     Non-recombining chromosomes, such as the Y chromosome in male heterogamtic species or the W chromosome in species with female heterogamety are characterized by their loss of active genes. In XY systems, this degeneration of the Y chromosome is coupled with the evolution of dosage compensation mechanisms to increase the expression of X-linked genes in males. Given the similarities between the degenerated Y and W chromosomes, one would expect similar dosage compensation mechanisms in ZW females, as W-linked copies of genes are also often missing or non-functional. However, the two independently evolved ZW systems that have so far been studied in detail, birds and Lepidoptera, lack dosage compensation. Although absence of dosage compensation may be a general feature of female-heterogametic species, it is also possible that the absence of DC mechanisms in these two clades is a mere coincidence, and the analysis of other independently evolved ZW systems is needed to confirm the pattern. We are analysing an independently evolved ZW system to test for this: Tephritids are dipteran insects closely related to Drosophila of which one genus, Tephritis, has a conserved ZW system. We are using Illumina sequencing to sequence the transcriptome of Tephritis species caught in the wild, in order to compare Z-linked and autosomal expression in males and females. If dosage compensation mechanisms are absent in these species, we expect ZW females, but not ZZ males, to show decreased Z-linked expression relative to the autosomal expression.

Gene trafficking on an evolving X chromosome
     Genes are distributed non-randomly across the genome. One intriguing pattern to emerge from genome-wide expression profiling is that genes with sex-biased expression (that is, genes that are differentially expressed between the sexes) show a biased distribution on sex chromosomes. In particular, male-biased genes are depleted from the Drosophila X chromosome, such that the X has become demasculinized. The deficiency of male-biased genes can partly be explained by movement of male genes off the X chromosome. The evolutionary forces underlying these patterns are controversial and may involve male germline X inactivation, sexual antagonism or dosage compensation mechanisms. Drosophila miranda has a newly formed sex chromosome system. Its neo-Y chromosome is in transition from an ordinary autosome to a degenerate Y. In response, the neo-X is evolving the stereotypical properties of a differentiated X, including the acquisition of partial dosage compensation and — as suggested by preliminary data—an excess of gene translocations originating from its neo-X. We are using
D. miranda to study the mechanisms of gene trafficking on an evolving X chromosome and its evolutionary causes in action using a comparative and functional genomics approach.

Mammals with clonal chromosomes.
     In most mammals, females have two X chromosomes, and males have an X and a Y chromosome (XX vs. XY). However, some rodents have very unusual sex chromosome systems. In the creeping vole,
Microtus oregoni, males are XY and females are X0 while in the mole vole, Ellobius lutescens, both males and females are X0. Thus, the X chromosome in these species is completely sheltered from recombination. Using population genetics and molecular evolution approaches, we are investigating the evolutionary origin of these bizarre sex chromosome systems.