1,721,059 research outputs found
Synthetic approaches to understanding biological constraints
Full text linkMicrobes can be readily cultured and their genomes can be easily manipulated. For these reasons, laboratory systems of unicellular organisms are increasingly used to develop and test theories about biological constraints, which manifest themselves at different levels of biological organization, from optimal gene-expression levels to complex individual and social behaviors. The quantitative description of biological constraints has recently advanced in several areas, such as the formulation of global laws governing the entire economy of a cell, the direct experimental measurement of the trade-offs leading to optimal gene expression, the description of naturally occurring fitness landscapes, and the appreciation of the requirements for a stable bacterial ecosystem.Alfred P. Sloan Foundation (Fellowship)Pew Charitable Trusts (Pew Scholars Program)National Science Foundation (U.S.) (NSF CAREER Award)National Institutes of Health (U.S.) (NIH R00 Pathway to Independence Award
Collective antibiotic resistance: mechanisms and implications
Full text linkIn collective resistance, microbial communities are able to survive antibiotic exposures that would be lethal to individual cells. In this review, we explore recent advances in understanding collective resistance in bacteria. The population dynamics of ‘cheating’ in a system with cooperative antibiotic inactivation have been described, providing insight into the demographic factors that determine resistance allele frequency in bacteria. Extensive work has elucidated mechanisms underlying collective resistance in biofilms and addressed questions about the role of cooperation in these structures. Additionally, recent investigations of ‘bet-hedging’ strategies in bacteria have explored the contributions of stochasticity and regulation to bacterial phenotypic heterogeneity and examined the effects of these strategies on community survival.United States. National Institutes of Health (6927557
The strength of genetic interactions scales weakly with mutational effects
Full text linkBackground:
Genetic interactions pervade every aspect of biology, from evolutionary theory, where they determine the accessibility of evolutionary paths, to medicine, where they can contribute to complex genetic diseases. Until very recently, studies on epistatic interactions have been based on a handful of mutations, providing at best anecdotal evidence about the frequency and the typical strength of genetic interactions. In this study, we analyze a publicly available dataset that contains the growth rates of over five million double knockout mutants of the yeast Saccharomyces cerevisiae.
Results:
We discuss a geometric definition of epistasis that reveals a simple and surprisingly weak scaling law for the characteristic strength of genetic interactions as a function of the effects of the mutations being combined. We then utilized this scaling to quantify the roughness of naturally occurring fitness landscapes. Finally, we show how the observed roughness differs from what is predicted by Fisher's geometric model of epistasis, and discuss the consequences for evolutionary dynamics.
Conclusions:
Although epistatic interactions between specific genes remain largely unpredictable, the statistical properties of an ensemble of interactions can display conspicuous regularities and be described by simple mathematical laws. By exploiting the amount of data produced by modern high-throughput techniques, it is now possible to thoroughly test the predictions of theoretical models of genetic interactions and to build informed computational models of evolution on realistic fitness landscapes.National Institutes of Health (U.S.) (Pathways to Independence Award)National Science Foundation (U.S.) (CAREER Award)Pew Charitable Trusts (Biomedical Scholars Program)Alfred P. Sloan Foundation (Research Fellowship
Selection favors incompatible signaling in bacteria
No full textA cooperative group can achieve more than the sum of its members. Evolution has taken advantage of this principle in most natural systems, from multicellular individuals to ant colonies. To do so, it has provided the members of cooperative groups with communication tools, which are critical for effective cooperation. For example, some ants form bridges with their bodies to help their nest-mates cross a gap. But this admirable behavior only makes sense when many ants mass along the same route; a lone scout that stayed put across a gap instead of wandering off in search for food would do a disservice to the colony. Similarly, many bacteria cooperate in ways that only make sense in large groups, for example secreting a sticky goo to keep bacteria together forming a biofilm, or a slippery one to help movement. To prevent wasting resources on these public goods when bacterial density is too low to have an advantage from them, many species measure local bacterial density using a mechanism called quorum sensing, and produce the public good only when numbers are high enough to make it count. This function of quorum sensing seems straightforward, but one piece of information does not quite make sense: in natural populations, different individuals have different—and incompatible—quorum-sensing machineries. If the bacteria are trying to coordinate with their neighbors, why do they use a different signaling system? In PNAS, Pollak et al. demonstrate an elegant answer to this question: a rare mutant with incompatible quorum-sensing machinery initially exploits the wild-type, but is able to cooperate with its own kind when common in the population
Oscillatory dynamics in a bacterial cross-protection mutualism
No full textCooperation between microbes can enable microbial communities to survive in harsh environments. Enzymatic deactivation of antibiotics, a common mechanism of antibiotic resistance in bacteria, is a cooperative behavior that can allow resistant cells to protect sensitive cells from antibiotics. Understanding how bacterial populations survive antibiotic exposure is important both clinically and ecologically, yet the implications of cooperative antibiotic deactivation on the population and evolutionary dynamics remain poorly understood, particularly in the presence of more than one antibiotic. Here, we show that two Escherichia coli strains can form an effective crossprotection mutualism, protecting each other in the presence of two antibiotics (ampicillin and chloramphenicol) so that the coculture can survive in antibiotic concentrations that inhibit growth of either strain alone. Moreover, we find that daily dilutions of the coculture lead to large oscillations in the relative abundance of the two strains, with
the ratio of abundances varying by nearly four orders of magnitude over the course of the 3-day period of the oscillation. At modest antibiotic concentrations, the mutualistic behavior enables long-term survival of the oscillating populations; however, at higher antibiotic concentrations, the oscillations destabilize the population, eventually leading to collapse. The two strains form a successful cross-protection mutualism without a period of coevolution, suggesting that similar mutualisms may arise during antibiotic treatment and in natural environments such as the soil.National Institutes of Health (U.S.) (Grant R01 GM102311-01)National Science Foundation (U.S.) (CAREER Award PHY- 1055154)Pew Charitable Trusts (Pew Scholars in the Biomedical Sciences Program Grant 2010-000224-007)National Institutes of Health (U.S.) (R00 Pathways to Independence Award GM085279-02)Alfred P. Sloan Foundation (Fellowship BR2011-066)Paul G. Allen Family Foundation (Allen Distinguished Investigator Award)National Institutes of Health (U.S.) (New Innovator Award DP2)National Science Foundation (U.S.). Graduate Research Fellowship Program (Grant 064596
Preferential interactions promote blind cooperation and informed defection
No full textIt is common sense that costs and benefits should be carefully weighed before deciding on a course of action. However, we often disapprove of people who do so, even when their actual decision benefits us. For example, we prefer people who directly agree to do us a favor over those who agree only after securing enough information to ensure that the favor will not be too costly. Why should we care about how people make their decisions, rather than just focus on the decisions themselves? Current models show that punishment of information gathering can be beneficial because it forces blind decisions, which under some circumstances enhances cooperation. Here we show that aversion to information gathering can be beneficial even in the absence of punishment, due to a different mechanism: preferential interactions with reliable partners. In a diverse population where different people have different—and unknown—preferences, those who seek additional information before agreeing to cooperate reveal that their preferences are close to the point where they would choose not to cooperate. Blind cooperators are therefore more likely to keep cooperating even if conditions change, and aversion to information gathering helps to interact preferentially with them. Conversely, blind defectors are more likely to keep defecting in the future, leading to a preference for informed defectors over blind ones. Both mechanisms—punishment to force blind decisions and preferential interactions—give qualitatively different predictions, which may enable experimental tests to disentangle them in real-world situations
A SLOWLY EVOLVING HOST MOVES FIRST IN SYMBIOTIC INTERACTIONS
Full text linkSymbiotic relationships, both parasitic and mutualistic, are ubiquitous in nature. Understanding how these symbioses evolve, from bacteria and their phages to humans and our gut microflora, is crucial in understanding how life operates. Often, symbioses consist of a slowly evolving host species with each host only interacting with its own subpopulation of symbionts. The Red Queen hypothesis describes coevolutionary relationships as constant arms races with each species rushing to evolve an advantage over the other, suggesting that faster evolution is favored. Here, we use a simple game theoretic model of host–symbiont coevolution that includes population structure to show that if the symbionts evolve much faster than the host, the equilibrium distribution is the same as it would be if it were a sequential game where the host moves first against its symbionts. For the slowly evolving host, this will prove to be advantageous in mutualisms and a handicap in antagonisms. The result follows from rapid symbiont adaptation to its host and is robust to changes in the parameters, even generalizing to continuous and multiplayer games. Our findings provide insight into a wide range of symbiotic phenomena and help to unify the field of coevolutionary theory.National Institutes of Health (U.S.) (K99 Pathways to Independence Award
Range expansions transition from pulled to pushed waves as growth becomes more cooperative in an experimental microbial population
No full textRange expansions are becoming more frequent due to environmental changes and rare long-distance dispersal, often facilitated by anthropogenic activities. Simple models in theoretical ecology explain many emergent properties of range expansions, such as a constant expansion velocity, in terms of organism-level properties such as growth and dispersal rates. Testing these quantitative predictions in natural populations is difficult because of large environmental variability. Here, we used a controlled microbial model system to study range expansions of populations with and without intraspecific cooperativity. For noncooperative growth, the expansion dynamics were dominated by population growth at the low-density front, which pulled the expansion forward. We found these expansions to be in close quantitative agreement with the classical theory of pulled waves by Fisher [Fisher RA (1937) Ann Eugen 7(4):355–369] and Skellam [Skellam JG (1951) Biometrika 38(1-2):196–218], suitably adapted to our experimental system. However, as cooperativity increased, the expansions transitioned to being pushed, that is, controlled by growth and dispersal in the bulk as well as in the front. Given the prevalence of cooperative growth in nature, understanding the effects of cooperativity is essential to managing invading species and understanding their evolution.National Science Foundation (U.S.). Graduate Research Fellowship ProgramNational Institutes of Health (U.S.) (NIH Director's New Innovator Award)National Science Foundation (U.S.) (NSF CAREER Award)Paul G. Allen Family Foundation (Allen Distinguished Investigator Award
Phenotypic states become increasingly sensitive to perturbations near a bifurcation in a synthetic gene network
Full text linkMicroorganisms often exhibit a history-dependent phenotypic response after exposure to a stimulus which can be imperative for proper function. However, cells frequently experience unexpected environmental perturbations that might induce phenotypic switching. How cells maintain phenotypic states in the face of environmental fluctuations remains an open question. Here, we use environmental perturbations to characterize the resilience of phenotypic states in a synthetic gene network near a critical transition. We find that far from the critical transition an environmental perturbation may induce little to no phenotypic switching, whereas close to the critical transition the same perturbation can cause many cells to switch phenotypic states. This loss of resilience was observed for perturbations that interact directly with the gene circuit as well as for a variety of generic perturbations-such as salt, ethanol, or temperature shocks-that alter the state of the cell more broadly. We obtain qualitatively similar findings in natural gene circuits, such as the yeast GAL network. Our findings illustrate how phenotypic memory can become destabilized by environmental variability near a critical transition.National Institutes of Health (U.S.) (Director's New Innovator Award
Spatial dilemmas of diffusible public goods
Full text linkThe emergence of cooperation is a central question in evolutionary biology. Microorganisms often cooperate by producing a chemical resource (a public good) that benefits other cells. The sharing of public goods depends on their diffusion through space. Previous theory suggests that spatial structure can promote evolution of cooperation, but the diffusion of public goods introduces new phenomena that must be modeled explicitly. We develop an approach where colony geometry and public good diffusion are described by graphs. We find that the success of cooperation depends on a simple relation between the benefits and costs of the public good, the amount retained by a producer, and the average amount retained by each of the producer’s neighbors. These quantities are derived as analytic functions of the graph topology and diffusion rate. In general, cooperation is favored for small diffusion rates, low colony dimensionality, and small rates of decay of the public good. DOI: http://dx.doi.org/10.7554/eLife.01169.001Version of Recor
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