Biology subjects

Michael M. Desai

Publications and source records attributed to Michael M. Desai.

4 recordsLinked to original sources

bioRxiv2016

Evolution of mutation rates in rapidly adapting asexual populations

Mutator and antimutator alleles often arise and spread in both natural microbial populations and laboratory evolution experiments. The evolutionary dynamics of these mutation rate modifiers are determined by indirect selection on linked beneficial and deleterious mutations. These indirect selection pressures have been the focus of much earlier theoretical and empirical work, but we still have a limited analytical understanding of how the interplay between hitchhiking and deleterious load influences the fates of modifier alleles. Our understanding is particularly limited when clonal interference is common, which is the regime of primary interest in laboratory microbial evolution experiments. Here, we calculate the fixation probability of a mutator or antimutator allele in a rapidly adapting asexual population, and we show how this quantity depends on the population size, the beneficial and deleterious mutation rates, and the strength of a typical driver mutation. In the absence of deleterious mutations, we find that clonal interference enhances the fixation probability of mutators, even as they provide a diminishing benefit to the overall rate of adaptation. When deleterious mutations are included, natural selection pushes the population towards a stable mutation rate that can be suboptimal for the adaptation of the population as a whole. The approach to this stable mutation rate is not necessarily monotonic, and selection can favor mutator and antimutator alleles that overshoot the stable mutation rate by substantial amounts.

Evolutionary Biology↗

bioRxiv2015

The fate of a mutation in a fluctuating environment

Natural environments are never truly constant, but the evolutionary implications of temporally varying selection pressures remain poorly understood. Here we investigate how the fate of a new mutation in a fluctuating environment depends on the dynamics of environmental variation and on the selective pressures in each condition. We find that even when a mutation experiences many environmental epochs before fixing or going extinct, its fate is not necessarily determined by its time-averaged selective effect. Instead, environmental variability reduces the efficiency of selection across a broad parameter regime, rendering selection unable to distinguish between mutations that are substantially beneficial and substantially deleterious on average. Temporal fluctuations can also dramatically increase fixation probabilities, often making the details of these fluctuations more important than the average selection pressures acting on each new mutation. For example, mutations that result in a tradeoff between conditions but are strongly deleterious on average can nevertheless be more likely to fix than mutations that are always neutral or beneficial. These effects can have important implications for patterns of molecular evolution in variable environments, and they suggest that it may often be difficult for populations to maintain specialist traits, even when their loss leads to a decline in time-averaged fitness.

Evolutionary Biology↗

bioRxiv2015

Inexpensive Multiplexed Library Preparation for Megabase-Sized Genomes

Whole-genome sequencing has become an indispensible tool of modern biology. However, the cost of sample preparation relative to the cost of sequencing remains high, especially for small genomes where the former is dominant. Here we present a protocol for the rapid and inexpensive preparation of hundreds of multiplexed genomic libraries for Illumina sequencing. By carrying out the Nextera tagmentation reaction in small volumes, replacing costly reagents with cheaper equivalents, and omitting unnecessary steps, we achieve a cost of library preparation of $8 per sample, approximately 6 times cheaper than the widely-used Nextera XT protocol. Furthermore, our procedure takes less than 5 hours for 96 samples and uses nanograms of genomic DNA. Many hundreds of samples can then be pooled on the same HiSeq lane via custom barcodes. Our method is especially useful for re-sequencing of large numbers of full microbial or viral genomes, including those from evolution experiments, genetic screens, and environmental samples.

Genomics↗

bioRxiv2014

The evolutionarily stable distribution of fitness effects

The distribution of fitness effects of new mutations (the DFE) is a key parameter in determining the course of evolution. This fact has motivated extensive efforts to measure the DFE or to predict it from first principles. However, just as the DFE determines the course of evolution, the evolutionary process itself constrains the DFE. Here, we analyze a simple model of genome evolution in a constant environment in which natural selection drives the population toward a dynamic steady state where beneficial and deleterious substitutions balance. The distribution of fitness effects at this steady state is stable under further evolution, and provides a natural null expectation for the DFE in a population that has evolved in a constant environment for a long time. We calculate how the shape of the evolutionarily stable DFE depends on the underlying population genetic parameters. We show that, in the absence of epistasis, the ratio of beneficial to deleterious mutations of a given fitness effect obeys a simple relationship independent of population genetic details. Finally, we analyze how the stable DFE changes in the presence of a simple form of diminishing returns epistasis.

Evolutionary Biology↗