Thinking too positive? Revisiting current methods of population genetic selection inference.

In the age of next-generation sequencing, the availability of increasing amounts and improved quality of data at decreasing cost ought to allow for a better understanding of how natural selection is shaping the genome than ever before. However, alternative forces, such as demography and background selection (BGS), obscure the footprints of positive selection that we would like to identify. In this review, we illustrate recent developments in this area, and outline a roadmap for improved selection inference. We argue (i) that the development and obligatory use of advanced simulation tools is necessary for improved identification of selected loci, (ii) that genomic information from multiple time points will enhance the power of inference, and (iii) that results from experimental evolution should be utilized to better inform population genomic studies.

The consequences of not accounting for background selection in demographic inference.

Recently, there has been increased awareness of the role of background selection (BGS) in both data analysis and modelling advances. However, BGS is still difficult to take into account because of tractability issues with simulations and difficulty with nonequilibrium demographic models. Often, simple rescaling adjustments of effective population size are used. However, there has been neither a proper characterization of how BGS could bias or shift inference when not properly taken into account, nor a thorough analysis of whether rescaling is a sufficient solution. Here, we carry out extensive simulations with BGS to determine biases and behaviour of demographic inference using an approximate Bayesian approach. We find that results can be positively misleading with significant bias, and describe the parameter space in which BGS models replicate observed neutral nonequilibrium expectations.

Inferring the age of a fixed beneficial allele.

Estimating the age and strength of beneficial alleles is central to understanding how adaptation proceeds in response to changing environmental conditions. Several haplotype-based estimators exist for inferring the age of segregating beneficial mutations. Here, we develop an approximate Bayesian-based approach that rather estimates these parameters for fixed beneficial mutations in single populations. We integrate a range of existing diversity, site frequency spectrum, haplotype- and linkage disequilibrium-based summary statistics. We show that for strong selective sweeps on de novo mutations the method can estimate allele age and selection strength even in nonequilibrium demographic scenarios. We extend our approach to models of selection on standing variation, and co-infer the frequency at which selection began to act upon the mutation. Finally, we apply our method to estimate the age and selection strength of a previously identified mutation underpinning cryptic colour adaptation in a wild deer mouse population, and compare our findings with previously published estimates as well as with geological data pertaining to the presumed shift in selective pressure.

Rooted triple consensus and anomalous gene trees.

BACKGROUND: Anomalous gene trees (AGTs) are gene trees with a topology different from a species tree that are more probable to observe than congruent gene trees. In this paper we propose a rooted triple approach to finding the correct species tree in the presence of AGTs. RESULTS: Based on simulated data we show that our method outperforms the extended majority rule consensus strategy, while still resolving the species tree. Applying both methods to a metazoan data set of 216 genes, we tested whether AGTs substantially interfere with the reconstruction of the metazoan phylogeny. CONCLUSION: Evidence of AGTs was not found in this data set, suggesting that erroneously reconstructed gene trees are the most significant challenge in the reconstruction of phylogenetic relationships among species with current data. The new method does however rule out the erroneous reconstruction of deep or poorly resolved splits in the presence of lineage sorting.

PopPlanner: visually constructing demographic models for simulation.

UNLABELLED: Currently there are a number of coalescent simulation programs that support a wide range of features, such as arbitrary demographic models, migration, and sub structure. Defining the model is done typically with either text files or command line switches. Although this has proven to be a powerful method of defining models of high complexity, it is often error prone and difficult to read without familiarity both with command lines and the program in question. A intuitive GUI based population structure program that can both read and write applicable command lines would dramatically simplify the construction, modification, and error checking of such models by a wider user base. RESULTS: PopPlanner is a tool to both construct and inspect complicated demographic models visually with a GUI where the user's primary interaction is through mouse gestures. Because of their popularity, we focus on ms and by extension msms, command line coalescent simulation programs. Our program can be used to find errors with existing command lines, or to build original command lines. Furthermore, the graphical output supports a number of editing and output features including export of publication quality figures.