Weldon Memorial Prize Lecture - Cracking the code of sexual reproduction and speciation

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In mammals, hybrids are often infertile, and this is thought to be a key driver of species formation – but how does this happen? In mammals, only a single speciation gene has so far been identified, in mice. In this talk I will talk about how this sterility is deeply connected to recombination, which shuffles mutations into new combinations, and to the pairing of chromosomes, essential to ensure one of each pair is passed on to offspring, two fundamental processes which are very incompletely understood. I will describe our collaborative work that has revealed how specific DNA sequences, which differ between all species so far examined, “code” for possible recombination sites, and identified key genes involved. Remarkably, simply modifying this code fully reverses hybrid sterility, in several cases.

Evolution of this code occurs extraordinarily rapidly both in cis and in trans, driving diverse phenomena: it explains hybrid sterility in mice, the origins of many human diseases, and why different human populations have differing recombination landscapes. The study of hybrid mice has led to an improved understanding of an enduring biological mystery: how do homologous chromosomes precisely align, finding their exact partners among billions of genetic bases of DNA within the cell? We speculate that this explains why, in most studied species, recombination occurs in only a tiny fraction of the genome, in “hotspots”, and discuss a range of evolutionary implications.

Professor Simon Myers is a member of the Department of Statistics, the Wellcome Trust Centre for Human Genetics and St John’s College, in Oxford. He has spent much of his career in Oxford, as well as several years spent at Harvard and the Broad Institute of MIT/Harvard. Although his original degree is in mathematics, his labs’ research has gradually broadened to combine the development of novel statistical techniques to investigate genetic data with experimental work. His research is diverse but centers around the study of genetic variation, its drivers and its impacts, for example revealing the timing and impacts on our DNA of many human migration events such as the Mongol empire, and Anglo-Saxon migrations. Another key research strand is the study of meiosis and its key defining features, namely recombination and the pairing of homologous chromosomes, and their connections to speciation in mammals. This has discovered a number of the key genes involved in the earliest steps of these processes, including some of the most rapidly evolving genes in the human genome. For his work, Professor Myers has been awarded the Genetics Society Balfour prize, and the Royal Society Francis Crick medal and lecture.