Inference of gene flow in the process of speciation: Efficient maximum-likelihood implementation of a generalised isolation-with-migration model.

The 'isolation with migration' (IM) model has been extensively used in the literature to detect gene flow during the process of speciation. In this model, an ancestral population split into two or more descendant populations which subsequently exchanged migrants at a constant rate until the present. Of course, the assumption of constant gene flow until the present is often over-simplistic in the context of speciation. In this paper, we consider a 'generalised IM' (GIM) model: a two-population IM model in which migration rates and population sizes are allowed to change at some point in the past. By developing a maximum-likelihood implementation of this model, we enable inference on both historical and contemporary rates of gene flow between two closely related populations or species. The GIM model encompasses both the standard two-population IM model and the 'isolation with initial migration' (IIM) model as special cases, as well as a model of secondary contact. We examine for simulated data how our method can be used, by means of likelihood ratio tests or AIC scores, to distinguish between the following scenarios of population divergence: (a) divergence in complete isolation; (b) divergence with a period of gene flow followed by isolation; (c) divergence with a period of isolation followed by secondary contact; (d) divergence with ongoing gene flow. Our method is based on the coalescent and is suitable for data sets consisting of the number of nucleotide differences between one pair of DNA sequences at each of a large number of independent loci. As our method relies on an explicit expression for the likelihood, it is computationally very fast.

Identification of Prognostic Phenotypes of Esophageal Adenocarcinoma in 2 Independent Cohorts.

BACKGROUND & AIMS: Most patients with esophageal adenocarcinoma (EAC) present with de novo tumors. Although this could be due to inadequate screening strategies, the precise reason for this observation is not clear. We compared survival of patients with prevalent EAC with and without synchronous Barrett esophagus (BE) with intestinal metaplasia (IM) at the time of EAC diagnosis. METHODS: Clinical data were studied using Cox proportional hazards regression to evaluate the effect of synchronous BE-IM on EAC survival independent of age, sex, TNM stage, and tumor location. We analyzed data from a cohort of patients with EAC from the Mayo Clinic (n=411; 203 with BE and IM) and a multicenter cohort from the United Kingdom (n=1417; 638 with BE and IM). RESULTS: In the Mayo cohort, BE with IM had a reduced risk of death compared to patients without BE and IM (hazard ratio [HR] 0.44; 95% CI, 0.34-0.57; P<.001). In a multivariable analysis, BE with IM was associated with longer survival independent of patient age or sex, tumor stage or location, and BE length (adjusted HR, 0.66; 95% CI, 0.5-0.88; P=.005). In the United Kingdom cohort, patients BE and IM had a reduced risk of death compared with those without (HR, 0.59; 95% CI, 0.5-0.69; P<.001), with continued significance in multivariable analysis that included patient age and sex and tumor stage and tumor location (adjusted HR, 0.77; 95% CI, 0.64-0.93; P=.006). CONCLUSION: Two types of EAC can be characterized based on the presence or absence of BE. These findings could increase our understanding the etiology of EAC, and be used in management and prognosis of patients.

Hybrid asexuality as a primary postzygotic barrier between nascent species: On the interconnection between asexuality, hybridization and speciation.

Although sexual reproduction is ubiquitous throughout nature, the molecular machinery behind it has been repeatedly disrupted during evolution, leading to the emergence of asexual lineages in all eukaryotic phyla. Despite intensive research, little is known about what causes the switch from sexual reproduction to asexuality. Interspecific hybridization is one of the candidate explanations, but the reasons for the apparent association between hybridization and asexuality remain unclear. In this study, we combined cross-breeding experiments with population genetic and phylogenomic approaches to reveal the history of speciation and asexuality evolution in European spined loaches (Cobitis). Contemporary species readily hybridize in hybrid zones, but produce infertile males and fertile but clonally reproducing females that cannot mediate introgressions. However, our analysis of exome data indicates that intensive gene flow between species has occurred in the past. Crossings among species with various genetic distances showed that, while distantly related species produced asexual females and sterile males, closely related species produce sexually reproducing hybrids of both sexes. Our results suggest that hybridization leads to sexual hybrids at the initial stages of speciation, but as the species diverge further, the gradual accumulation of reproductive incompatibilities between species could distort their gametogenesis towards asexuality. Interestingly, comparative analysis of published data revealed that hybrid asexuality generally evolves at lower genetic divergences than hybrid sterility or inviability. Given that hybrid asexuality effectively restricts gene flow, it may establish a primary reproductive barrier earlier during diversification than other "classical" forms of postzygotic incompatibilities. Hybrid asexuality may thus indirectly contribute to the speciation process.

Inference of Gene Flow in the Process of Speciation: An Efficient Maximum-Likelihood Method for the Isolation-with-Initial-Migration Model.

The isolation-with-migration (IM) model is commonly used to make inferences about gene flow during speciation, using polymorphism data. However, it has been reported that the parameter estimates obtained by fitting the IM model are very sensitive to the model's assumptions-including the assumption of constant gene flow until the present. This article is concerned with the isolation-with-initial-migration (IIM) model, which drops precisely this assumption. In the IIM model, one ancestral population divides into two descendant subpopulations, between which there is an initial period of gene flow and a subsequent period of isolation. We derive a very fast method of fitting an extended version of the IIM model, which also allows for asymmetric gene flow and unequal population sizes. This is a maximum-likelihood method, applicable to data on the number of segregating sites between pairs of DNA sequences from a large number of independent loci. In addition to obtaining parameter estimates, our method can also be used, by means of likelihood-ratio tests, to distinguish between alternative models representing the following divergence scenarios: (a) divergence with potentially asymmetric gene flow until the present, (b) divergence with potentially asymmetric gene flow until some point in the past and in isolation since then, and (c) divergence in complete isolation. We illustrate the procedure on pairs of Drosophila sequences from ∼30,000 loci. The computing time needed to fit the most complex version of the model to this data set is only a couple of minutes. The R code to fit the IIM model can be found in the supplementary files of this article.