A New Isolation with Migration Model along Complete Genomes Infers Very Different Divergence Processes among Closely Related Great Ape Species

We present a hidden Markov model (HMM) for inferring gradual isolation between two populations during speciation, modelled as a time interval with restricted gene flow. The HMM describes the history of adjacent nucleotides in two genomic sequences, such that the nucleotides can be separated by recombination, can migrate between populations, or can coalesce at variable time points, all dependent on the parameters of the model, which are the effective population sizes, splitting times, recombination rate, and migration rate. We show by extensive simulations that the HMM can accurately infer all parameters except the recombination rate, which is biased downwards. Inference is robust to variation in the mutation rate and the recombination rate over the sequence and also robust to unknown phase of genomes unless they are very closely related. We provide a test for whether divergence is gradual or instantaneous, and we apply the model to three key divergence processes in great apes: (a) the bonobo and common chimpanzee, (b) the eastern and western gorilla, and (c) the Sumatran and Bornean orang-utan. We find that the bonobo and chimpanzee appear to have undergone a clear split, whereas the divergence processes of the gorilla and orang-utan species occurred over several hundred thousands years with gene flow stopping quite recently. We also apply the model to the Homo/Pan speciation event and find that the most likely scenario involves an extended period of gene flow during speciation. Author Summary: Next-generation sequencing technology has enabled the generation of whole-genome data for many closely related species. For population genetic inference we have sequenced many loci, but only in a few individuals. We present a new method that allows inference of the divergence process based on two closely related genomes, modelled as gradual isolation in an isolation with migration model. This allows estimation of the initial time of restricted gene flow, the cessation of gene flow, as well as the population sizes, migration rates, and recombination rates. We show by simulations that the parameter estimation is accurate with genome-wide data and use the model to disentangle the divergence processes among three sets of closely related great ape species: bonobo/chimpanzee, eastern/western gorillas, and Sumatran/Bornean orang-utans. We find allopatric speciation for bonobo and chimpanzee and non-allopatric speciation for the gorillas and orang-utans. We also consider the split between humans and chimpanzees/bonobos and find evidence for non-allopatric speciation, similar to that within gorillas and orang-utans.