Bachelor of Science, Yale University (2010)
Doctor of Philosophy, Harvard University (2016)
Stephen Quake, Postdoctoral Faculty Sponsor
Chance and necessity in the pleiotropic consequences of adaptation for budding yeast.
Nature ecology & evolution
Mutations that a population accumulates during evolution in one 'home' environment may cause fitness gains or losses in other environments. Such pleiotropic fitness effects determine the evolutionary fate of the population in variable environments and can lead to ecological specialization. It is unclear how the pleiotropic outcomes of evolution are shaped by the intrinsic randomness of the evolutionary process and by the deterministic variation in selection pressures across environments. Here, to address this question, we evolved 20 replicate populations of the yeast Saccharomyces cerevisiae in 11 laboratory environments and measured their fitness across multiple conditions. We found that evolution led to diverse pleiotropic fitness gains and losses, driven by multiple types of mutations. Approximately 60% of this variation is explained by the home environment of a clone and the most common parallel genetic changes, whereas about 40% is attributed to the stochastic accumulation of mutations whose pleiotropic effects are unpredictable. Although populations are typically specialized to their home environment, generalists also evolved in almost all of the conditions. Our results suggest that the mutations that accumulate during evolution incur a variety of pleiotropic costs and benefits with different probabilities. Thus, whether a population evolves towards a specialist or a generalist phenotype is heavily influenced by chance.
View details for DOI 10.1038/s41559-020-1128-3
View details for PubMedID 32152531
Heterogeneous T cell motility behaviors emerge from a coupling between speed and turning in vivo.
T cells in vivo migrate primarily via undirected random walks, but it remains unresolved how these random walks generate an efficient search. Here, we use light sheet microscopy of T cells in the larval zebrafish as a model system to study motility across large populations of cells over hours in their native context. We show that cells do not perform Levy flight; rather, there is substantial cell-to-cell variability in speed, which persists over timespans of a few hours. This variability is amplified by a correlation between speed and directional persistence, generating a characteristic cell behavioral manifold that is preserved under a perturbation to cell speeds, and seen in Mouse T cells and Dictyostelium. Together, these effects generate a broad range of length scales over which cells explore in vivo.
View details for DOI 10.7554/eLife.53933
View details for PubMedID 32427565
Genetic variation in adaptability and pleiotropy in budding yeast
Evolution can favor organisms that are more adaptable, provided that genetic variation in adaptability exists. Here, we quantify this variation among 230 offspring of a cross between diverged yeast strains. We measure the adaptability of each offspring genotype, defined as its average rate of adaptation in a specific environmental condition, and analyze the heritability, predictability, and genetic basis of this trait. We find that initial genotype strongly affects adaptability and can alter the genetic basis of future evolution. Initial genotype also affects the pleiotropic consequences of adaptation for fitness in a different environment. This genetic variation in adaptability and pleiotropy is largely determined by initial fitness, according to a rule of declining adaptability with increasing initial fitness, but several individual QTLs also have a significant idiosyncratic role. Our results demonstrate that both adaptability and pleiotropy are complex traits, with extensive heritable differences arising from naturally occurring variation.
View details for DOI 10.7554/eLife.27167
View details for Web of Science ID 000409363600001
View details for PubMedID 28826486
View details for PubMedCentralID PMC5580887
Genomic investigations of evolutionary dynamics and epistasis in microbial evolution experiments
CURRENT OPINION IN GENETICS & DEVELOPMENT
2015; 35: 33–39
Microbial evolution experiments enable us to watch adaptation in real time, and to quantify the repeatability and predictability of evolution by comparing identical replicate populations. Further, we can resurrect ancestral types to examine changes over evolutionary time. Until recently, experimental evolution has been limited to measuring phenotypic changes, or to tracking a few genetic markers over time. However, recent advances in sequencing technology now make it possible to extensively sequence clones or whole-population samples from microbial evolution experiments. Here, we review recent work exploiting these techniques to understand the genomic basis of evolutionary change in experimental systems. We first focus on studies that analyze the dynamics of genome evolution in microbial systems. We then survey work that uses observations of sequence evolution to infer aspects of the underlying fitness landscape, concentrating on the epistatic interactions between mutations and the constraints these interactions impose on adaptation.
View details for DOI 10.1016/j.gde.2015.08.008
View details for Web of Science ID 000366900600006
View details for PubMedID 26370471
View details for PubMedCentralID PMC4710057
Fate of a mutation in a fluctuating environment
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2015; 112 (36): E5021–E5028
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 trade-off 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.
View details for DOI 10.1073/pnas.1505406112
View details for Web of Science ID 000360994900009
View details for PubMedID 26305937
View details for PubMedCentralID PMC4568713
Global epistasis makes adaptation predictable despite sequence-level stochasticity
2014; 344 (6191): 1519–22
Epistatic interactions between mutations can make evolutionary trajectories contingent on the chance occurrence of initial mutations. We used experimental evolution in Saccharomyces cerevisiae to quantify this contingency, finding differences in adaptability among 64 closely related genotypes. Despite these differences, sequencing of 104 evolved clones showed that initial genotype did not constrain future mutational trajectories. Instead, reconstructed combinations of mutations revealed a pattern of diminishing-returns epistasis: Beneficial mutations have consistently smaller effects in fitter backgrounds. Taken together, these results show that beneficial mutations affecting a variety of biological processes are globally coupled; they interact strongly, but only through their combined effect on fitness. As a consequence, fitness evolution follows a predictable trajectory even though sequence-level adaptation is stochastic.
View details for DOI 10.1126/science.1250939
View details for Web of Science ID 000337889900051
View details for PubMedID 24970088
View details for PubMedCentralID PMC4314286
Dynamic Mutation-Selection Balance as an Evolutionary Attractor
2012; 191 (4): 1309–U377
The vast majority of mutations are deleterious and are eliminated by purifying selection. Yet in finite asexual populations, purifying selection cannot completely prevent the accumulation of deleterious mutations due to Muller's ratchet: once lost by stochastic drift, the most-fit class of genotypes is lost forever. If deleterious mutations are weakly selected, Muller's ratchet can lead to a rapid degradation of population fitness. Evidently, the long-term stability of an asexual population requires an influx of beneficial mutations that continuously compensate for the accumulation of the weakly deleterious ones. Hence any stable evolutionary state of a population in a static environment must involve a dynamic mutation-selection balance, where accumulation of deleterious mutations is on average offset by the influx of beneficial mutations. We argue that such a state can exist for any population size N and mutation rate U and calculate the fraction of beneficial mutations, ε, that maintains the balanced state. We find that a surprisingly low ε suffices to achieve stability, even in small populations in the face of high mutation rates and weak selection, maintaining a well-adapted population in spite of Muller's ratchet. This may explain the maintenance of mitochondria and other asexual genomes.
View details for DOI 10.1534/genetics.112.141291
View details for Web of Science ID 000309000500020
View details for PubMedID 22661327
View details for PubMedCentralID PMC3416009
Deformation of an Elastic Substrate by a Three-Phase Contact Line
PHYSICAL REVIEW LETTERS
2011; 106 (18): 186103
Young's classic analysis of the equilibrium of a three-phase contact line ignores the out-of-plane component of the liquid-vapor surface tension. While it is expected that this unresolved force is balanced by the elastic response of the solid, a definitive analysis has remained elusive because of an apparent divergence of stress at the contact line. While a number of theories have been presented to cut off the divergence, none of them have provided reasonable agreement with experimental data. We measure surface and bulk deformation of a thin elastic film near a three-phase contact line using fluorescence confocal microscopy. The out-of-plane deformation is well fit by a linear elastic theory incorporating an out-of-plane restoring force due to the surface tension of the solid substrate. This theory predicts that the deformation profile near the contact line is scale-free and independent of the substrate elastic modulus.
View details for DOI 10.1103/PhysRevLett.106.186103
View details for Web of Science ID 000290304800017
View details for PubMedID 21635105