"It does not deny that change, when it occurs, may be mediated by natural selection, but it holds that constraints restrict possible paths and modes of change so strongly that the constraints themselves become much the most interesting aspect of evolution."
-Gould and Lewontin, 1979
Understanding the effects of selection at linked sites
Understanding the effects of selection at linked sites: current population genetic approaches assume complete neutrality, i.e., they assume that new mutations that do not contribute to fitness (i.e., neutral alleles) segregate independently of other nearby selected mutations. Several experimental and population-genetic studies have now confirmed that most new mutations that occur on functionally important sites are deleterious. Thus, despite the drastic prevalence of deleterious mutations, their effects on nearby linked sites remain relatively under-studied and are largely ignored when performing population-genetic inference (e.g. Figure 1). We are interested in understanding how linked effects of selection against deleterious and for beneficial alleles affects genome-wide patterns of variation and how we can account for their effects when performing evolutionary inference.
Inference of selection and demography
A primary challenge in population genetics has been to understand how evolutionary processes like selection, mutation, recombination, and genetic drift determined by population size changes jointly shape patterns of genome-wide variation and how to disentangle their individual contributions using population-genetic data. This is essential to better understand the demographic and selective history of organisms of interest, for instance, uncovering the historical migration patterns of our ancestors and predicting the mode and tempo of adaptation in pathogenic organisms and so on. Moreover, advances in accurately disentangling the contributing evolutionary processes are also essential to answer broader questions in evolutionary biology, like the relative importance of adaptive vs non-adaptive processes in determining evolutionary outcomes. However, as multiple evolutionary processes can shape patterns of variation in a similar manner, disentangling their individual contributions can be a difficult task. We are interested in developing methods to perform joint inference of parameters of evolutionary processes from population-genetic data, especially those of the demographic history of natural populations and the distribution of fitness effects of new mutations.
Population genetics in species with compact genomes
Organisms can vary widely in how much of their genome is under selective constraints. For instance, while human genomes are estimated to have about 5-8% of the genome functional, ~40-60% of the D. melanogaster genome and ~70-90% of the genome in unicellular organisms can be functionally important. We are interested in understanding patterns of variation and in performing evolutionary inference in species with highly compact genomes where direct and linked effects of selection are pervasive, confounding patterns generated by other evolutionary forces. These approaches will be particularly useful to understand the demographic and selective history of pathogenic species, that usually have densely-packed genomes and a complex natural history.
Evolution of gene duplicates
Gene duplication is an important source of evolutionary novelty, resulting in new gene functions, expansion of gene families and contributing to the emergence of new species. Segmental duplications have been found to occur at high rates in most eukaryotic genomes, while whole-genome duplications have occurred in the ancestors of many eukaryotes. What are the consequences and fate of these duplications? While gene duplicates have been studied at phylogenic timescales pretty extensively, much less is understood about how population genetic parameters play a role in their retention/loss. We are interested in questions like how long does it take for a gene duplicate to be lost in a population, i.e., what is the time to fixation of a loss-of-function mutation or null allele of a duplicate? Do gene duplicates experience different selective forces in a population? Why are some species more likely to retain gene duplicates than others? What are the fitness effects of new gene duplicates?