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Mahilkar, A.

Publications and source records attributed to Mahilkar, A..

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Resource presentation dictates genetic and phenotypic adaptation in yeast.

Environments shape adaptive trajectories of populations, often leading to adaptive parallelism in identical, and divergence in different environments. However, how does the likelihood of these possibilities change with minute changes in the environment? In this study, we evolve Saccharomyces cerevisiae in environments which only differed in how sugar source is presented to the population. In one set of populations, carbon was presented as a mixture of glucose-galactose, and in the other, as melibiose, a glucose-galactose disaccharide. Since the two environments only differ in how the two monosaccharides are packaged, we call these environments "synonymous". Our results show that subtle changes in environments change the targets of selection between the two sets of evolved populations. However, despite different adaptive responses, pleiotropic effects of adaptation are largely predictable. Genome sequencing results demonstrate that small changes in the environment also strongly dictates the genetic basis of adaptation.

evolutionary biology↗

Adaptive and pleiotropic effects of evolution in synonymous sugar environments.

Adaptation to an environment is enabled by the accumulation of beneficial mutations. When adapted populations are shifted to other environments, the byproduct or pleiotropic fitness effects of these mutations can be wide-ranged. Since there exists no molecular framework to quantify relatedness of environments, predicting pleiotropic effects based on adaptation has been challenging. In this work, we ask if evolution in highly similar environments elicits correlated adaptive and pleiotropic responses. We evolve replicate populations of Escherichia coli in non-stressful environments that contain either a mixture of glucose and galactose, lactose, or melibiose as the source of carbon. We term these similar sugars as "synonymous", since lactose and melibiose are disaccharides made up of glucose and galactose. Therefore, the evolution environments differed only in the way carbon was presented to the bacterial population. After 300 generations of evolution, we see that the adaptive responses of these populations are not predictable. We investigate the pleiotropic effects of adaptation in a range of non-synonymous environments, and show that despite uncorrelated adaptive changes, the nature of pleiotropic effects is largely predictable based on the fitness of the ancestor in the non-home environments. Overall, our results highlight how subtle changes in the environment can alter adaptation, but despite sequence-level variations, pleiotropy is qualitatively predictable. Lay SummaryIn nature, evolution in "similar" environments is believed to elicit identical responses. For example, the arctic fox and ptarmigan, which are two unrelated species living in the arctic, have evolved to turn white in the winters. They did not evolve this ability because they from the common ancestor, but because the environment favoured this trait. In this work, we ask what happens to evolving populations if there are minute changes in the environment, and what are the consequences of adapting in these environments that are "almost identical", or as we call them, "synonymous". We evolve replicate populations of the bacteria E. coli in three synonymous environments, and quantify their ability to grow in both synonymous and non-synonymous environments. We see that evolution does not proceed in an identical fashion in these populations, and that each environment favours a different trait. However, interestingly, in non-synonymous environments, these three sets of populations perform almost identically, and their growth is qualitatively predictable. Our results show that even simple and subtle changes in the environment can act as drivers of biodiversity.

evolutionary biology↗

Empirical evidence of resource dependent evolution of payoff matrices in Saccharomyces cerevisiae populations.

In evolutionary game theory, a relative comparison of the cost and benefit associated with obtaining a resource, called payoff, is used as an indicator of fitness of an organism. Such payoff matrices are used to understand complex inter-species and intra-species interactions like cooperation, mutualism, and altruism. In the absence of any empirical data, the evolution of these payoff matrices has been investigated theoretically by tweaking well-established game theory models. In this paper, we present empirical evidence of three types of resource-dependent changes in the payoff matrices of evolving Saccharomyces cerevisiae populations. We show that depending on the carbon source and participating genotypes, the payoff matrix could either (a) evolve quantitatively yet maintain a cheater-cooperator game, (b) change qualitatively such that the cheater-cooperator game collapses, or (c) change qualitatively to result in the birth of a cheater-cooperator game. Our results highlight the need to consider the dynamic nature of payoff matrices while making even short-term predictions about population interactions and dynamics.

evolutionary biology↗

Rapid evolution of pre-zygotic reproductive barriers in allopatric populations.

Adaptive divergence leading to speciation is the major evolutionary process generating diversity in life forms. The most commonly observed form of speciation is allopatric speciation which requires that gene flow be prevented between populations by physical or temporal barriers, as they adapt to their respective environments. Eventually, these adaptive responses drive the populations far apart in the genotypic space such that individuals from the two populations become reproductively isolated. A widely accepted theory is that speciation simply occurs as a by-product of adaptive response of the populations1,2. Several ecological and laboratory examples of allopatric speciation exist3-6. However, we know little about the nature (pre- or post-zygotic) of barriers that arise first in this process. Understanding the first barriers that arise between populations is key, as populations diverge towards becoming distinct species. In recent years, fungi been used as model organisms to answer questions related to evolution of reproductive isolation3,7-9. Here we show rapid evolution of pre-zygotic barriers between allopatric yeast populations. We further demonstrate that these pre-zygotic barriers arise due to altered mating kinetics of the evolved population. Moreover, our non-adaptive evolution experiments with yeast under limited selection pressure also show rapid emergence of reproductive isolation. Overall, our results show that evolution of pre-zygotic reproductive barriers can occur as result of natural selection or drift. These barriers result because of altered mating kinetics or mate preference. One sentence summaryPre-zygotic barriers to gene flow can arise due to adaptation or drift.

evolutionary biology↗

Selection in a growing bacterial/yeast colony biases results of mutation accumulation experiments.

Mutations provide the raw material for natural selection to act. Therefore, understanding the variety and relative frequency of different type of mutations is critical to understanding the nature of genetic diversity in a population. Mutation accumulation (MA) experiments have been used in this context to estimate parameters defining mutation rates, distribution of fitness effects (DFE), and spectrum of mutations. MA experiments performed with organisms such as Drosophila have an effective population size of one. However, in MA experiments with bacteria and yeast, a single founder is allowed to grow to a size of a colony (~108). The effective population size in these experiments is of the order of 10. In this scenario, while it is assumed that natural selection plays a minimal role in dictating the dynamics of colony growth and therefore, the MA experiment; this effect has not been tested explicitly. In this work, we simulate colony growth and perform an MA experiment, and demonstrate that selection ensures that, in an MA experiment, fraction of all mutations that are beneficial is over represented by a factor greater than two. The DFE of beneficial and deleterious mutations are accurately captured in an MA experiment. We show that the effect of selection in a growing colony varies non-monotonically and that, in the face of natural selection dictating an MA experiment, estimates of mutation rate of an organism is not trivial. We perform experiments with 160 MA lines of E. coli, and demonstrate that rate of change of mean fitness is a non-monotonic function of the colony size, and that selection acts differently in different sectors of a growing colony. Overall, we demonstrate that the results of MA experiments need to be revisited taking into account the action of selection in a growing colony.

evolutionary biology↗

Public-good driven release of heterogeneous resources leads to genotypic diversification of an isogenic yeast population in melibiose.

Adaptive diversification of an isogenic population, and its molecular basis has been a subject of a number of studies in the last few years. Microbial populations offer a relatively convenient model system to study this question. In this context, an isogenic population of bacteria (E. coli, B. subtilis, and Pseudomonas) has been shown to lead to genetic diversification in the population, when propagated for a number of generations. This diversification is known to occur when the individuals in the population have access to two or more resources/environments, which are separated either temporally or spatially. Here, we report adaptive diversification in an isogenic population of yeast, S. cerevisiae, when propagated in an environment containing melibiose as the carbon source. The diversification is driven due to a public good, enzyme -galactosidase, leading to hydrolysis of melibiose into two distinct resources, glucose and galactose. The diversification is driven by a mutations at a single locus, in the GAL3 gene in the GAL/MEL regulon in the yeast.

microbiology↗

Predicting experimental designs leading to rewiring of transcription program and evolution of anticipatory regulation in E. coli.

Environmental cues in an ecological niche are often temporal in nature. For instance, in temperate climates, temperature is higher in daytime compared to during night. In response to these temporal cues, bacteria have been known to exhibit anticipatory regulation, whereby they trigger response to a yet to appear cue, anticipating its actual arrival in the near future. Such an anticipatory response in known to enhance Darwinian fitness, and hence, is likely an important feature of regulatory networks in microorganisms. However, the conditions under which an anticipatory response evolves as an adaptive response are not known. In this work, we develop a quantitative model to study response of a population to two temporal environmental cues, and predict variables which are likely important for evolution of anticipatory regulatory response. We follow this with experimental evolution of E. coli in alternating environments of a pentose sugar, rhamnose, and an oxidative stress molecule, paraquat for more than 800 generations. We demonstrate that growth in this cyclical environment leads to evolution of anticipatory regulation, whereby, exposure to rhamnose leads to partial induction of the oxidative stress response regulon. As a result, pre-exposure to rhamnose leads to a greater fitness in paraquat environment. Overall, we show that in niches where environmental stimuli have a cyclical nature, anticipatory regulation can evolve as an adaptive strategy, in a time course of a few hundred generations. This contributes to our understanding of how environment shapes the topology of regulatory networks in an organism.

microbiology↗