Our paper "Frequent adaptation and the McDonald-Kreitman test" has just been published in PNAS. The McDonald-Kreitman (MK) test is the basis of most modern approaches to measure the rate of adaptation from population genomic data. This test was used to argue that in some organisms, such as Drosophila, the rate of adaptation is surprisingly high. However, the MK test, and in fact most of the current machinery of population genetics, relies on the assumption that adaptation is rare so that the effects of selective sweeps on linked variation can be neglected. We test this assumption using a powerful forward simulation and show that the MK test is severely biased even when the rate of adaptation is only moderate. The bigger claim of our paper is that the effects of linked selection cannot be simply swept under the rug by introducing effective parameters, such as effective population size or effective strength of selection, and then using these effective parameters in formulae derived from the diffusion approximation under the assumption of free recombination. Given that most of our estimates of the key evolutionary parameters are still obtained from methods based on this paradigm, we argue that it is crucial to verify whether they are robust to linkage effects.
Our paper about "The McDonald-Kreitman Test and its Extensions under Frequent Adaptation: Problems and Solutions" is featured on Haldane's Sieve. A preprint of the paper can be downloaded on arXiv. In this paper, we performed forward simulations under realistic gene-structure and selection scenarios to investigate whether linkage effects from recurrent selective sweeps impinge on the ability of the McDonald-Kreitman (MK) test to infer the rate of positive selection from polymorphism and divergence data. We find that in the presence of slightly deleterious mutations, MK estimates often severely underestimate the true rate of adaptation and that already under intermediate rates of adaptation, genetic draft substantially distorts the site frequency spectra at neutral and functional sites from the expectations under mutation-selection-drift balance.
Today our paper about "Genome patterns of selection and introgression of haplotypes in natural populations of the house mouse (mus musculus)" has been published in PLoS Genetics. You can access the paper here. In this paper, we detect abundant evidence for recent positive selection in mice, including loci that are known to be involved in genetic diseases in humans. Unexpectedly, we also find a high proportion of gene exchange between populations that have long been separated. This finding supports the notion that hybridization and transfer of alleles can significantly contribute to new genetic material subject to positive selection.
I gave a talk at SMBE 2012 today about the "McDonald-Kreitman test and its extnesions under frequent adaptation: problems and solutions". I felt that the talk was very well received and sparked some interesting discussions. We have just submitted a manuscript about this story. It was nice to get feedback from people such as Peter Keightley and Adam Eyre-Walker, who's methods we investigate in this project. The slides from my presentation can be downloaded here.
Our paper on "Genome Patterns of Selection and Introgression of Haplotypes in Natural Populations of the House Mouse (Mus musculus)" has been accepted at PLoS Genetics today. Yay! The authors on this paper are Fabian Staubach, Anna Lorenc, myself, Kun Tang, Dmitri A. Petrov and Diethard Tautz. More on this paper to follow soon.>
Today I gave a talk at the Radcliffe Institute for Advanced Studies at Harvard University during the workshop Selection in Population Genetics, which was organized by Michael Desai and Aleksandra Walczak. In my one hour presentation I talked about "McDonald-Kreitman test under frequent adaptation: problems and solutions". The slides from my talk can be downloaded here.
Richard's and my paper on "Measuring the strength of selective sweeps from deep population diversity data" has finally been accepted for publication in Genetics. You can access the paper here. In this paper, we developed a new approach to measure the selection coefficients of selective sweeps. In contrast to previous methods, which typically analyze the reduction in diversity caused by a sweep, our method utilizes the novel variation that arises from mutations occurring on the sweeping haplotypes. Compared to these standard approaches our estimator requires much shorter sequences but sampled at high population depth in order to capture low-frequency variants; given such data, it consistently outperforms the standard approaches. When applying this method to HIV populations we observed several examples of strong adaptation involving both hard and soft sweeps.
My abstract for this year's SMBE conference in Dublin, Ireland, has been accepted for an oral presentation. I will talk in the symposium Adaptive evolution and selective sweeps on Monday, June 25th. Luckily I also got awarded a travel fellowship ($1500) for the conference.
I gave a talk in the Statistics and Genomics seminar at UC Berkeley today. During my one hour presentation I talked about "Heterozygote advantage as a natural consequence of adaptation in diploids". The slides from my talk can be downloaded here.
Our paper on Heterozygote advantage as a natural consequences of adaptation has been published in PNAS. In this paper, Diamantis, Ben, Dmitri and I show that adaptation should often drive beneficial variants only to intermediate population frequencies where they can persist in a balanced state with other variants. This feature of adaptation in diploids emerges naturally from the primary importance of the fitness of heterozygotes for the invasion of new adaptive mutations. We formalize this result in the framework of Fisher's influential geometric model of adaptation. We find that in diploids, adaptation should often proceed through a succession of short-lived balanced states that maintain substantially higher levels of phenotypic and fitness variation in the population compared with classic adaptive walks. In fast-changing environments, this variation produces a diversity advantage that allows diploids to remain better adapted compared with haploids despite the disadvantage associated with the presence of unfit homozygotes. The short-lived balanced states arising during adaptive walks should be mostly invisible to current scans for long-term balancing selection. Instead, they should leave signatures of incomplete selective sweeps, which do appear to be common in many species. Our results also raise the possibility that balancing selection, as a natural consequence of frequent adaptation, might play a more prominent role among the forces maintaining genetic variation than is commonly recognized.