scholarly journals Higher-fitness yeast genotypes are less robust to deleterious mutations

Science ◽  
2019 ◽  
Vol 366 (6464) ◽  
pp. 490-493 ◽  
Author(s):  
Milo S. Johnson ◽  
Alena Martsul ◽  
Sergey Kryazhimskiy ◽  
Michael M. Desai

Natural selection drives populations toward higher fitness, but second-order selection for adaptability and mutational robustness can also influence evolution. In many microbial systems, diminishing-returns epistasis contributes to a tendency for more-fit genotypes to be less adaptable, but no analogous patterns for robustness are known. To understand how robustness varies across genotypes, we measure the fitness effects of hundreds of individual insertion mutations in a panel of yeast strains. We find that more-fit strains are less robust: They have distributions of fitness effects with lower mean and higher variance. These differences arise because many mutations have more strongly deleterious effects in faster-growing strains. This negative correlation between fitness and robustness implies that second-order selection for robustness will tend to conflict with first-order selection for fitness.

2019 ◽  
Author(s):  
Milo S. Johnson ◽  
Alena Martsul ◽  
Sergey Kryazhimskiy ◽  
Michael M. Desai

AbstractNatural selection drives populations towards higher fitness, but second-order selection for adaptability and mutational robustness can also influence the dynamics of adaptation. In many microbial systems, diminishing returns epistasis contributes to a tendency for more-fit genotypes to be less adaptable, but no analogous patterns for robustness are known. To understand how robustness varies across genotypes, we measure the fitness effects of hundreds of individual insertion mutations in a panel of yeast strains. We find that more-fit strains are less robust: they have distributions of fitness effects (DFEs) with lower mean and higher variance. These shifts in the DFE arise because many mutations have more strongly deleterious effects in faster-growing strains. This negative correlation between fitness and robustness implies that second-order selection for robustness will tend to conflict with first-order selection for fitness.


Science ◽  
2020 ◽  
Vol 370 (6521) ◽  
pp. eabb5962
Author(s):  
Jia Zheng ◽  
Ning Guo ◽  
Andreas Wagner

Natural selection can promote or hinder a population’s evolvability—the ability to evolve new and adaptive phenotypes—but the underlying mechanisms are poorly understood. To examine how the strength of selection affects evolvability, we subjected populations of yellow fluorescent protein to directed evolution under different selection regimes and then evolved them toward the new phenotype of green fluorescence. Populations under strong selection for the yellow phenotype evolved the green phenotype most rapidly. They did so by accumulating mutations that increase both robustness to mutations and foldability. Under weak selection, neofunctionalizing mutations rose to higher frequency at first, but more frequent deleterious mutations undermined their eventual success. Our experiments show how selection can enhance evolvability by enhancing robustness and create the conditions necessary for evolutionary success.


Science ◽  
2011 ◽  
Vol 331 (6023) ◽  
pp. 1433-1436 ◽  
Author(s):  
R. J. Woods ◽  
J. E. Barrick ◽  
T. F. Cooper ◽  
U. Shrestha ◽  
M. R. Kauth ◽  
...  

2021 ◽  
Author(s):  
Milo Johnson ◽  
Michael M. Desai

As an adapting population traverses the fitness landscape, its local neighborhood (i.e., the collection of fitness effects of single-step mutations) can change shape because of interactions with mutations acquired during evolution. These changes to the distribution of fitness effects can affect both the rate of adaptation and the accumulation of deleterious mutations. However, while numerous models of fitness landscapes have been proposed in the literature, empirical data on how this distribution changes during evolution remains limited. In this study, we directly measure how the fitness landscape neighborhood changes during laboratory adaptation. Using a barcode-based mutagenesis system, we measure the fitness effects of 91 specific gene disruption mutations in genetic backgrounds spanning 8,000-10,000 generations of evolution in two constant environments. We find that the mean of the distribution of fitness effects decreases in one environment, indicating a reduction in mutational robustness, but does not change in the other. We show that these distribution-level patterns result from biases in variable patterns of epistasis at the level of individual mutations, including fitness-correlated and idiosyncratic epistasis.


1997 ◽  
Vol 36 (04/05) ◽  
pp. 315-318 ◽  
Author(s):  
K. Momose ◽  
K. Komiya ◽  
A. Uchiyama

Abstract:The relationship between chromatically modulated stimuli and visual evoked potentials (VEPs) was considered. VEPs of normal subjects elicited by chromatically modulated stimuli were measured under several color adaptations, and their binary kernels were estimated. Up to the second-order, binary kernels obtained from VEPs were so characteristic that the VEP-chromatic modulation system showed second-order nonlinearity. First-order binary kernels depended on the color of the stimulus and adaptation, whereas second-order kernels showed almost no difference. This result indicates that the waveforms of first-order binary kernels reflect perceived color (hue). This supports the suggestion that kernels of VEPs include color responses, and could be used as a probe with which to examine the color visual system.


2017 ◽  
Vol 9 (3) ◽  
pp. 17-30
Author(s):  
Kelly James Clark

In Branden Thornhill-Miller and Peter Millican’s challenging and provocative essay, we hear a considerably longer, more scholarly and less melodic rendition of John Lennon’s catchy tune—without religion, or at least without first-order supernaturalisms (the kinds of religion we find in the world), there’d be significantly less intra-group violence. First-order supernaturalist beliefs, as defined by Thornhill-Miller and Peter Millican (hereafter M&M), are “beliefs that claim unique authority for some particular religious tradition in preference to all others” (3). According to M&M, first-order supernaturalist beliefs are exclusivist, dogmatic, empirically unsupported, and irrational. Moreover, again according to M&M, we have perfectly natural explanations of the causes that underlie such beliefs (they seem to conceive of such natural explanations as debunking explanations). They then make a case for second-order supernaturalism, “which maintains that the universe in general, and the religious sensitivities of humanity in particular, have been formed by supernatural powers working through natural processes” (3). Second-order supernaturalism is a kind of theism, more closely akin to deism than, say, Christianity or Buddhism. It is, as such, universal (according to contemporary psychology of religion), empirically supported (according to philosophy in the form of the Fine-Tuning Argument), and beneficial (and so justified pragmatically). With respect to its pragmatic value, second-order supernaturalism, according to M&M, gets the good(s) of religion (cooperation, trust, etc) without its bad(s) (conflict and violence). Second-order supernaturalism is thus rational (and possibly true) and inconducive to violence. In this paper, I will examine just one small but important part of M&M’s argument: the claim that (first-order) religion is a primary motivator of violence and that its elimination would eliminate or curtail a great deal of violence in the world. Imagine, they say, no religion, too.Janusz Salamon offers a friendly extension or clarification of M&M’s second-order theism, one that I think, with emendations, has promise. He argues that the core of first-order religions, the belief that Ultimate Reality is the Ultimate Good (agatheism), is rational (agreeing that their particular claims are not) and, if widely conceded and endorsed by adherents of first-order religions, would reduce conflict in the world.While I favor the virtue of intellectual humility endorsed in both papers, I will argue contra M&M that (a) belief in first-order religion is not a primary motivator of conflict and violence (and so eliminating first-order religion won’t reduce violence). Second, partly contra Salamon, who I think is half right (but not half wrong), I will argue that (b) the religious resources for compassion can and should come from within both the particular (often exclusivist) and the universal (agatheistic) aspects of religious beliefs. Finally, I will argue that (c) both are guilty, as I am, of the philosopher’s obsession with belief. 


2009 ◽  
Vol 74 (1) ◽  
pp. 43-55 ◽  
Author(s):  
Dennis N. Kevill ◽  
Byoung-Chun Park ◽  
Jin Burm Kyong

The kinetics of nucleophilic substitution reactions of 1-(phenoxycarbonyl)pyridinium ions, prepared with the essentially non-nucleophilic/non-basic fluoroborate as the counterion, have been studied using up to 1.60 M methanol in acetonitrile as solvent and under solvolytic conditions in 2,2,2-trifluoroethan-1-ol (TFE) and its mixtures with water. Under the non- solvolytic conditions, the parent and three pyridine-ring-substituted derivatives were studied. Both second-order (first-order in methanol) and third-order (second-order in methanol) kinetic contributions were observed. In the solvolysis studies, since solvent ionizing power values were almost constant over the range of aqueous TFE studied, a Grunwald–Winstein equation treatment of the specific rates of solvolysis for the parent and the 4-methoxy derivative could be carried out in terms of variations in solvent nucleophilicity, and an appreciable sensitivity to changes in solvent nucleophilicity was found.


Author(s):  
Uriah Kriegel

Brentano’s theory of judgment serves as a springboard for his conception of reality, indeed for his ontology. It does so, indirectly, by inspiring a very specific metaontology. To a first approximation, ontology is concerned with what exists, metaontology with what it means to say that something exists. So understood, metaontology has been dominated by three views: (i) existence as a substantive first-order property that some things have and some do not, (ii) existence as a formal first-order property that everything has, and (iii) existence as a second-order property of existents’ distinctive properties. Brentano offers a fourth and completely different approach to existence talk, however, one which falls naturally out of his theory of judgment. The purpose of this chapter is to present and motivate Brentano’s approach.


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