  Speciation is of fundamental importance to understanding the huge diversity
of life on Earth. In contrast to current phenomenological models, we develop a
biophysically motivated approach to study speciation involving the co-evolution
of protein binding DNA for two geographically isolated populations. Our results
predict that, despite neutral diffusion of hybrids in trait space, smaller
populations have a higher rate of speciation, due to sequence entropy poising
populations more closely to incompatible regions of phenotype space. A key
lesson of this work is that non-trivial contributions of sequence entropy give
rise to a strong population size dependence on speciation rates.
