Biology subjects

Chapel, M. E.

Publications and source records attributed to Chapel, M. E..

2 recordsLinked to original sources

bioRxiv2025

Evolutionary simulations reveal role for genomic recombination in the evolution of gene regulatory network complexity and robustness

The gene regulatory networks (GRNs) of eukaryotes are dramatically more complex than the GRNs of prokaryotes, but we lack a complete picture of the selective pressures that have shaped this difference. Here, we use a biochemically informed model of gene regulation to simulate GRN evolution and explore the role that reproductive strategy plays in shaping regulatory complexity. We find that recombining and non-recombining populations converge to the same level of complexity, even in the absence of selection. However, recombination modifies the rate at which complexity emerges, accelerating convergence to the complexity plateau in changing environments while slowing the process in static environments. Our results suggest that, rather than being under direct selection, regulatory complexity may emerge as a byproduct of other evolutionary processes. These results highlight how reproductive strategy and environmental change interact to influence evolutionary trajectories.

bioinformatics↗

bioRxiv2025

Variant effects depend on polygenic background: experimental, clinical, and evolutionary implications

Both rare and common genetic variants contribute to human disease, and emerging evidence suggests that they combine additively to influence disease liability. However, the non-linear relationship between disease liability and disease prevalence means that risk variants may have more severe phenotypic consequences in high-risk polygenic backgrounds and minimal impact in low-risk backgrounds, resulting in uneven selection across the population. As a result, selection coefficients may be better modeled as distributions that differ across populations, time, environments, and individuals rather than single values. Further, the number of genes contributing to a trait and epistasis between alleles enhance negative selection due to the increased variance pushing more individuals to phenotypic extremes. Because disease-relevant phenotypes may be masked in certain genetic backgrounds, polygenic background should be considered when characterizing the molecular underpinnings of complex traits.

genomics↗