The causes and consequences of sex differences in meiotic recombination.

When animals and plants produce eggs or sperm, their matching chromosomes pair up and exchange large segments of DNA via chromosomal “crossovers”. This is known as meiotic recombination, and it is a fundamental part of sexual reproduction. Recombination is beneficial: it ensures the correct number of chromosomes are transmitted into eggs and sperm; it also brings together beneficial gene-copies (“alleles”) onto the same chromosome, allowing populations to purge harmful mutations and respond faster to selection. However, recombination is also costly: too many crossovers can introduce harmful mutations, and can break apart beneficial alleles that are already linked together. These trade-offs were thought to constrain recombination rates to a narrow range. In reality, we see a huge diversity of recombination rates in nature: they differ within and between species, individuals, chromosomes, and even chromosomal regions. Understanding how and why this variation has evolved has important implications for evolutionary biology, fertility research, and animal and plant breeding. Yet, despite a century of theoretical attention, the evolution of recombination rates remains a major unsolved question in biology. Females and males often have very different rates and patterns of recombination, a phenomenon known as “heterochiasmy”. Recombination rates can be higher in females (e.g., in humans, deer) or males (e.g., in sheep, macaques), and this can vary along the genome, with female- or male-biased recombination “hotspots”. There are many evolutionary theories to explain heterochiasmy, but none are supported with real-world data. A major oversight is that theories rarely consider the molecular basis of female and male recombination - they occur in different tissues (ovaries and testes) at different times of development, are controlled by different genes, and have different effects on fertility. Therefore, if we want to understand the evolution of recombination more broadly, we must first understand the molecular causes and evolutionary consequences of variation in females and males. Our team will investigate this question using genomic data from a long-term study of house sparrows (Passer domesticus). Female sparrows have more crossovers than males, but recombination can be female- or male-biased along the genome. We hypothesise that when DNA unravels to transcribe and express genes, meiotic proteins use this window of opportunity to bind to the DNA and form crossovers. Therefore, differences in gene expression and DNA “accessibility” during meiosis may be a mechanism to explain why heterochiasmy is so common. Furthermore, if some genes are only expressed in meiosis in one sex, we hypothesise that these genes will be less constrained to the other sex, meaning they can evolve faster and lead to rapid evolution of heterochiasmy. Our project will use newly-emerging and cutting-edge sequencing technologies that quantify gene expression and DNA accessibility within individual meiotic cells in both sexes. First, we will determine if sex-biased recombination hotspots correspond to regions of high expression and accessibility in their meiotic cells. Then, we will identify genes that have similar or different effects on recombination between the sexes, and determine if those that are different show evidence of faster evolution in their DNA sequences. Our innovative study will be a first direct examination of the molecular causes and evolutionary consequences of heterochiasmy. It will greatly improve our understanding of a fundamental biological process that is crucial to fertility and inheritance, and broaden our knowledge of the factors that affect recombination rate evolution in nature.