Effect and interaction of mutation and recombination in the dynamics of genetic variation in modern chickens

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Resolving how genetic variation is maintained in closed populations under directional selection is one of the fundamental, yet still open questions in quantitative genetics. Addressing this question has also vital implications for the sustainability of genetic improvement programmes that underpin global staple food production systems. Considerable research effort has focused on studying how selection reduces genetic variation and how its footprint can be identified in the genome. Little effort has been placed to study how genetic variation is de-novo created and shuffled across generations. The reason is that until now, it was not feasible to track mutation, the evolutionary force creating new genetic variation, on the large-scale that analysis required, due to technological and economic constraints. The only option available to geneticists was to rely on low precision estimates for the mutation rate, since they mostly arose from small scale studies in experimental populations. These parameters then would be used in models aiming to describe the dynamics of genetic variation, which were based on many theoretical assumptions due to lack of data on the observed rate of mutation. The uncertainty of the parameters used, combined with our limited understanding of the interplay of forces on genetic variation, reduce the power of our current models to capture the underlying processes and therefore, explain why "there is still no clear resolution on the evolutionary forces responsible for the maintenance of variation", as one of the gold standard textbooks in Quantitative Genetics (Lynch and Walsh, 2018) emphatically states. The main hypothesis of this proposal is that the rate of creation and shuffling of genetic variation can counterbalance the effects of selection, genetic drift and inbreeding in finite closed populations, such as the elite breeding populations. Our goal is to take a data-driven approach to quantify with unprecedented accuracy the mutation and recombination processes that could explain how genetic variation appears to be maintained in closed populations that are under intense directional selection. To achieve this aim, we will use a unique genomic repository consisting of hundreds of thousands of birds (either sequenced in high-depth or genotyped with SNP arrays) extending over 25 generations with full pedigree and phenotypic information to study how genetic variation is maintained over time. This dataset gives us the required power to precisely estimate important parameters, such as how many mutational events occur per generation, where they tend to occur across the genome, and how the new genetic variation due to mutation balances its removal. As our data extend over many generations, we will have the power to track both mutations and chromosomal segments through the pedigree in order to remove false positive observations that can inflate estimates. Our study will also focus on quantifying recombination, as the force shuffling genetic variation, and we will explore its interplay with mutation. Finally, we will apply our more precise estimates to update theoretical expectations on where selection limits may lay and thus we will aim to reconcile theoretical predictions and observations. Beyond the potential to address the key question of how genetic variation is maintained, our findings could be directly applicable across animal and plant breeding organisations to improve the resilience and sustainability of their genetic improvement programmes.