The Behavior of Molecular Measures of Natural Selection after a Change in Population Size

ABSTRACTA common model to describe natural selection at the molecular level is the nearly neutral theory, which emphasizes the importance of mutations with slightly deleterious fitness effects as they have a chance to get fixed due to genetic drift. Since genetic drift is stronger in smaller than in larger populations, a negative relationship between molecular measures of selection and population size is expected within the nearly neutral theory. Originally, this hypothesis was formulated under equilibrium conditions. A change in population size, however, pushes the selection-drift balance off equilibrium leading to alterations in the efficacy of selection. To investigate the nonequilibrium behavior, we relate measures of natural selection and genetic drift to each other, considering both, measures of micro- and macroevolution. Specifically, we use a Poisson random field framework to model πN/πS and ω as time-dependent measures of selection and assess genetic drift by an effective population size. This analysis reveals a clear deviation from the expected equilibrium selection-drift balance during nonequilibrium periods. Moreover, we find that microevolutionary measures quickly react to a change in population size and reflect a recent change well, at the same time as they quickly lose the knowledge about it. Macroevolutionary measures, on the other hand, react more slowly to a change in population size but instead capture the influence of ancient changes longer. We therefore conclude that it is important to be aware of the different behaviors of micro- and macroevo- lutionary measures when making inference in empirical studies, in particular when comparing results between studies.

From Drift to Draft: How Much Do Beneficial Mutations Actually Contribute to Predictions of Ohta’s Slightly Deleterious Model of Molecular Evolution?

Since its inception in 1973, the slightly deleterious model of molecular evolution, also known as the nearly neutral theory of molecular evolution, remains a central model to explain the main patterns of DNA polymorphism in natural populations. This is not to say that the quantitative fit to data are perfect. A recent study used polymorphism data from Drosophila melanogaster to test whether, as predicted by the nearly neutral theory, the proportion of effectively neutral mutations depends on the effective population size (Ne). It showed that a nearly neutral model simply scaling with Ne variation across the genome could not alone explain the data, but that consideration of linked positive selection improves the fit between observations and predictions. In the present article, we extended the work in two main directions. First, we confirmed the observed pattern on a set of 59 species, including high-quality genomic data from 11 animal and plant species with different mating systems and effective population sizes, hence a priori different levels of linked selection. Second, for the 11 species with high-quality genomic data we also estimated the full distribution of fitness effects (DFE) of mutations, and not solely the DFE of deleterious mutations. Both Ne and beneficial mutations contributed to the relationship between the proportion of effectively neutral mutations and local Ne across the genome. In conclusion, the predictions of the slightly deleterious model of molecular evolution hold well for species with small Ne, but for species with large Ne, the fit is improved by incorporating linked positive selection to the model.

Reconstructing the history of variation in effective population size along phylogenies

The nearly-neutral theory predicts specific relations between effective population size (Ne), and patterns of divergence and polymorphism, which depend on the shape of the distribution of fitness effects (DFE) of new mutations. However, testing these relations is not straightforward since Ne is difficult to estimate in practice. For that reason, indirect proxies for Ne have often been used to test the nearly-neutral theory, although with mixed results. Here, we introduce an integrative comparative framework allowing for an explicit reconstruction of the phylogenetic history of Ne, thus leading to a quantitative test of the nearly-neutral theory and an independent estimation of the shape parameter of the DFE. We applied our method to primates, for which the nearly-neutral predictions were mostly verified. Estimates of the shape parameter were compatible with independent measures based on site frequency spectra. The reconstructed history of Ne in primates seems consistent with current knowledge and shows a clear phylogenetic structure at the super-family level. Altogether, our integrative framework provides a quantitative assessment of the role of Ne in modulating patterns of genetic variation, while giving a synthetic picture of the long-term trends in Ne variation across a group of species.

From drift to draft: How much do beneficial mutations actually contribute to predictions of Ohta’s slightly deleterious model of molecular evolution?

Since its inception in 1973 the slightly deleterious model of molecular evolution, aka the Nearly Neutral Theory of molecular evolution, remains a central model to explain the main patterns of DNA polymorphism in natural populations. This is not to say that the quantitative fit to data is perfect. In a recent study Castellanoet al. (2018) used polymorphism data from D. melanogaster to test whether, as predicted by the Nearly Neutral Theory, the proportion of effectively neutral mutations depends on the effective population size (Ne). They showed that a nearly neutral model simply scaling with Ne variation across the genome could not explain alone the data but that consideration of linked positive selection improves the fit between observations and predictions. In the present article we extended their work in two main directions. First, we confirmed the observed pattern on a set of 59 species, including high quality genomic data from 11 animal and plant species with different mating systems and effective population sizes, hence a priori different levels of linked selection. Second, for the 11 species with high quality genomic data we also estimated the full Distribution of Fitness Effects (DFE) of mutations, and not solely the DFE of deleterious mutations. Both Ne and beneficial mutations contributed to the relationship between the proportion of effectively neutral mutations and local Ne across the genome. In conclusion, the predictions of the slightly deleterious model of molecular evolution hold well for species with small Ne. But for species with large Ne the fit is improved by incorporating linked positive selection to the model.