%0 Journal Article %A Khatri, Bhavin S %A Goldstein, Richard A %D 2020 %T Biophysics and population size constrains speciation in an evolutionary model of developmental system drift. %U https://crick.figshare.com/articles/journal_contribution/Biophysics_and_population_size_constrains_speciation_in_an_evolutionary_model_of_developmental_system_drift_/11559768 %2 https://crick.figshare.com/ndownloader/files/20780898 %K Animals %K Biodiversity %K Biological Evolution %K Biophysical Phenomena %K Computational Biology %K Computer Simulation %K Epistasis, Genetic %K Female %K Genetic Association Studies %K Genetic Drift %K Genetic Fitness %K Genetic Speciation %K Genotype %K Male %K Models, Genetic %K Monte Carlo Method %K Phenotype %K Population Density %K Reproductive Isolation %K Bioinformatics %K 06 Biological Sciences %K 08 Information and Computing Sciences %K 01 Mathematical Sciences %X Developmental system drift is a likely mechanism for the origin of hybrid incompatibilities between closely related species. We examine here the detailed mechanistic basis of hybrid incompatibilities between two allopatric lineages, for a genotype-phenotype map of developmental system drift under stabilising selection, where an organismal phenotype is conserved, but the underlying molecular phenotypes and genotype can drift. This leads to number of emergent phenomenon not obtainable by modelling genotype or phenotype alone. Our results show that: 1) speciation is more rapid at smaller population sizes with a characteristic, Orr-like, power law, but at large population sizes slow, characterised by a sub-diffusive growth law; 2) the molecular phenotypes under weakest selection contribute to the earliest incompatibilities; and 3) pair-wise incompatibilities dominate over higher order, contrary to previous predictions that the latter should dominate. The population size effect we find is consistent with previous results on allopatric divergence of transcription factor-DNA binding, where smaller populations have common ancestors with a larger drift load because genetic drift favours phenotypes which have a larger number of genotypes (higher sequence entropy) over more fit phenotypes which have far fewer genotypes; this means less substitutions are required in either lineage before incompatibilities arise. Overall, our results indicate that biophysics and population size provide a much stronger constraint to speciation than suggested by previous models, and point to a general mechanistic principle of how incompatibilities arise the under stabilising selection for an organismal phenotype. %I The Francis Crick Institute