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https://www.readbyqxmd.com/read/29136190/the-genotype-phenotype-relationships-in-the-light-of-natural-selection
#1
Han Chen, Chung-I Wu, Xionglei He
Although any genotype-phenotype relationships are a result of evolution, little is known about how natural selection and neutral drift, two distinct driving forces of evolution, operate to shape the relationships. By analysing ∼500 yeast quantitative traits we reveal a basic "supervisor-worker" gene architecture underlying a trait. Supervisors are often identified by "perturbational" approaches (such as gene deletion), while workers, which usually show small and statistically insignificant deletion effects, are tracked primarily by "observational" approaches that examine the correlation between gene activity and trait value across a number of conditions...
November 9, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29130883/regulatory-network-structure-determines-patterns-of-intermolecular-epistasis
#2
Mato Lagator, Srdjan Sarikas, Hande Acar, Jonathan P Bollback, Călin C Guet
Most phenotypes are determined by molecular systems composed of specifically interacting molecules. However, unlike for individual components, little is known about the distributions of mutational effects of molecular systems as a whole. We ask how the distribution of mutational effects of a transcriptional regulatory system differs from the distributions of its components, by first independently, and then simultaneously, mutating a transcription factor and the associated promoter it represses. We find that the system distribution exhibits increased phenotypic variation compared to individual component distributions - an effect arising from intermolecular epistasis between the transcription factor and its DNA-binding site...
November 13, 2017: ELife
https://www.readbyqxmd.com/read/29100081/compensatory-mutations-and-epistasis-for-protein-function
#3
REVIEW
Jay F Storz
Adaptive protein evolution may be facilitated by neutral amino acid mutations that confer no benefit when they first arise but which potentiate subsequent function-altering mutations via direct or indirect structural mechanisms. Theoretical and empirical results indicate that such compensatory interactions (intramolecular epistasis) can exert a strong influence on trajectories of protein evolution. For this reason, assessing the form and prevalence of intramolecular epistasis and characterizing biophysical mechanisms of compensatory interaction are important research goals at the nexus of structural biology and molecular evolution...
November 5, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/29078365/molecular-ensembles-make-evolution-unpredictable
#4
Zachary R Sailer, Michael J Harms
Evolutionary prediction is of deep practical and philosophical importance. Here we show, using a simple computational protein model, that protein evolution remains unpredictable, even if one knows the effects of all mutations in an ancestral protein background. We performed a virtual deep mutational scan-revealing the individual and pairwise epistatic effects of every mutation to our model protein-and then used this information to predict evolutionary trajectories. Our predictions were poor. This is a consequence of statistical thermodynamics...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29045390/the-dynamics-of-molecular-evolution-over-60-000-generations
#5
Benjamin H Good, Michael J McDonald, Jeffrey E Barrick, Richard E Lenski, Michael M Desai
The outcomes of evolution are determined by a stochastic dynamical process that governs how mutations arise and spread through a population. However, it is difficult to observe these dynamics directly over long periods and across entire genomes. Here we analyse the dynamics of molecular evolution in twelve experimental populations of Escherichia coli, using whole-genome metagenomic sequencing at five hundred-generation intervals through sixty thousand generations. Although the rate of fitness gain declines over time, molecular evolution is characterized by signatures of rapid adaptation throughout the duration of the experiment, with multiple beneficial variants simultaneously competing for dominance in each population...
November 2, 2017: Nature
https://www.readbyqxmd.com/read/28902834/alternative-evolutionary-histories-in-the-sequence-space-of-an-ancient-protein
#6
Tyler N Starr, Lora K Picton, Joseph W Thornton
To understand why molecular evolution turned out as it did, we must characterize not only the path that evolution followed across the space of possible molecular sequences but also the many alternative trajectories that could have been taken but were not. A large-scale comparison of real and possible histories would establish whether the outcome of evolution represents an optimal state driven by natural selection or the contingent product of historical chance events; it would also reveal how the underlying distribution of functions across sequence space shaped historical evolution...
September 21, 2017: Nature
https://www.readbyqxmd.com/read/28578406/ancestral-protein-resurrection-and-engineering-opportunities-of-the-mamba-aminergic-toxins
#7
Guillaume Blanchet, Doria Alili, Adèle Protte, Gregory Upert, Nicolas Gilles, Livia Tepshi, Enrico A Stura, Gilles Mourier, Denis Servent
Mamba venoms contain a multiplicity of three-finger fold aminergic toxins known to interact with various α-adrenergic, muscarinic and dopaminergic receptors with different pharmacological profiles. In order to generate novel functions on this structural scaffold and to avoid the daunting task of producing and screening an overwhelming number of variants generated by a classical protein engineering strategy, we accepted the challenge of resurrecting ancestral proteins, likely to have possessed functional properties...
June 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28535292/adaptive-radiation-of-pseudomonas-fluorescens-sbw25-in-experimental-microcosms-provides-an-understanding-of-the-evolutionary-ecology-and-molecular-biology-of-a-l-interface-biofilm-formation
#8
Anna Koza, Anna Kusmierska, Kimberley McLaughlin, Olena Moshynets, Andrew J Spiers
Combined experimental evolutionary and molecular biology approaches have been used to investigate the adaptive radiation of Pseudomonas fluorescens SBW25 in static microcosms leading to the colonisation of the air-liquid interface by biofilm-forming mutants such as the Wrinkly Spreader (WS). In these microcosms, the ecosystem engineering of the early wild-type colonists establishes the niche space for subsequent WS evolution and colonisation. Random WS mutations occurring in the developing population that deregulate diguanylate cyclases and c-di-GMP homeostasis result in cellulose-based biofilms at the air-liquid interface...
July 3, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28533810/tc003132-is-essential-for-the-follicle-stem-cell-lineage-in-telotrophic-tribolium-oogenesis
#9
Matthias Teuscher, Nadi Ströhlein, Markus Birkenbach, Dorothea Schultheis, Michael Schoppmeier
BACKGROUND: Stem cells are undifferentiated cells with a potential for self-renewal, which are essential to support normal development and homeostasis. To gain insight into the molecular mechanisms underlying adult stem cell biology and organ evolution, we use the telotrophic ovary of the beetle Tribolium. To this end, we participated in a large-scale RNAi screen in the red flour beetle Tribolium, which identified functions in embryonic and postembryonic development for more than half of the Tribolium genes...
2017: Frontiers in Zoology
https://www.readbyqxmd.com/read/28250185/epistatic-interactions-influence-terrestrial-marine-functional-shifts-in-cetacean-rhodopsin
#10
Sarah Z Dungan, Belinda S W Chang
Like many aquatic vertebrates, whales have blue-shifting spectral tuning substitutions in the dim-light visual pigment, rhodopsin, that are thought to increase photosensitivity in underwater environments. We have discovered that known spectral tuning substitutions also have surprising epistatic effects on another function of rhodopsin, the kinetic rates associated with light-activated intermediates. By using absorbance spectroscopy and fluorescence-based retinal release assays on heterologously expressed rhodopsin, we assessed both spectral and kinetic differences between cetaceans (killer whale) and terrestrial outgroups (hippo, bovine)...
March 15, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28185903/the-thermodynamics-of-protein-aggregation-reactions-may-underpin-the-enhanced-metabolic-efficiency-associated-with-heterosis-some-balancing-selection-and-the-evolution-of-ploidy-levels
#11
REVIEW
B R Ginn
Identifying the physical basis of heterosis (or "hybrid vigor") has remained elusive despite over a hundred years of research on the subject. The three main theories of heterosis are dominance theory, overdominance theory, and epistasis theory. Kacser and Burns (1981) identified the molecular basis of dominance, which has greatly enhanced our understanding of its importance to heterosis. This paper aims to explain how overdominance, and some features of epistasis, can similarly emerge from the molecular dynamics of proteins...
July 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/27825296/resurrecting-ancestral-structural-dynamics-of-an-antiviral-immune-receptor-adaptive-binding-pocket-reorganization-repeatedly-shifts-rna-preference
#12
Charles Pugh, Oralia Kolaczkowski, Austin Manny, Bryan Korithoski, Bryan Kolaczkowski
BACKGROUND: Although resurrecting ancestral proteins is a powerful tool for understanding the molecular-functional evolution of gene families, nearly all studies have examined proteins functioning in relatively stable biological processes. The extent to which more dynamic systems obey the same 'rules' governing stable processes is unclear. Here we present the first detailed investigation of the functional evolution of the RIG-like receptors (RLRs), a family of innate immune receptors that detect viral RNA in the cytoplasm...
November 8, 2016: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/27714976/genetics-of-host-parasite-interactions-towards-a-comprehensive-dissection-of-drosophila-resistance-to-viral-infection
#13
Sara Magalhães, Élio Sucena
One of the major challenges in evolutionary biology is to unravel the genetic basis of adaptation. This issue has been gaining momentum in recent years with the accelerated development of novel genetic and genomic techniques and resources. In this issue of Molecular Ecology, Cogni et al. (2016) address the genetic basis of resistance to two viruses in Drosophila melanogaster using a panel of recombinant inbred lines with unprecedented resolution allowing detection of rare alleles and/or alleles of small effect...
October 2016: Molecular Ecology
https://www.readbyqxmd.com/read/27694971/the-evolution-of-antimicrobial-peptide-resistance-in-pseudomonas-aeruginosa-is-shaped-by-strong-epistatic-interactions
#14
Nicholas Jochumsen, Rasmus L Marvig, Søren Damkiær, Rune Lyngklip Jensen, Wilhelm Paulander, Søren Molin, Lars Jelsbak, Anders Folkesson
Colistin is an antimicrobial peptide that has become the only remaining alternative for the treatment of multidrug-resistant Gram-negative bacterial infections, but little is known of how clinical levels of colistin resistance evolve. We use in vitro experimental evolution and whole-genome sequencing of colistin-resistant Pseudomonas aeruginosa isolates from cystic fibrosis patients to reconstruct the molecular evolutionary pathways open for high-level colistin resistance. We show that the evolution of resistance is a complex, multistep process that requires mutation in at least five independent loci that synergistically create the phenotype...
October 3, 2016: Nature Communications
https://www.readbyqxmd.com/read/27678053/epistasis-and-pleiotropy-affect-the-modularity-of-the-genotype-phenotype-map-of-cross-resistance-in-hiv-1
#15
Robert Polster, Christos J Petropoulos, Sebastian Bonhoeffer, Frédéric Guillaume
The genotype-phenotype (GP) map is a central concept in evolutionary biology as it describes the mapping of molecular genetic variation onto phenotypic trait variation. Our understanding of that mapping remains partial, especially when trying to link functional clustering of pleiotropic gene effects with patterns of phenotypic trait co-variation. Only on rare occasions have studies been able to fully explore that link and tend to show poor correspondence between modular structures within the GP map and among phenotypes...
December 2016: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/27661780/using-long-term-experimental-evolution-to-uncover-the-patterns-and-determinants-of-molecular-evolution-of-an-escherichia-coli-natural-isolate-in-the-streptomycin-treated-mouse-gut
#16
Mathilde Lescat, Adrien Launay, Mohamed Ghalayini, Mélanie Magnan, Jérémy Glodt, Coralie Pintard, Sara Dion, Erick Denamur, Olivier Tenaillon
Although microbial ecology of the gut is now a major focus of interest, little is known about the molecular determinants of microbial adaptation in the gut. Experimental evolution coupled with whole-genome sequencing can provide insights of the adaptive process. In vitro experiments have revealed some conserved patterns: intermediate convergence, and epistatic interactions between beneficial mutations and mutations in global regulators. To test the relevance of these patterns and to identify the selective pressures acting in vivo, we have performed a long-term adaptation of an E...
April 2017: Molecular Ecology
https://www.readbyqxmd.com/read/27634870/gene-tree-discordance-can-generate-patterns-of-diminishing-convergence-over-time
#17
Fábio K Mendes, Yoonsoo Hahn, Matthew W Hahn
Phenotypic convergence is an exciting outcome of adaptive evolution, occurring when different species find similar solutions to the same problem. Unraveling the molecular basis of convergence provides a way to link genotype to adaptive phenotypes, but can also shed light on the extent to which molecular evolution is repeatable and predictable. Many recent genome-wide studies have uncovered a striking pattern of diminishing convergence over time, ascribing this pattern to the presence of intramolecular epistatic interactions...
December 2016: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/27194749/epistasis-and-the-dynamics-of-reversion-in-molecular-evolution
#18
David M McCandlish, Premal Shah, Joshua B Plotkin
Recent studies of protein evolution contend that the longer an amino acid substitution is present at a site, the less likely it is to revert to the amino acid previously occupying that site. Here we study this phenomenon of decreasing reversion rates rigorously and in a much more general context. We show that, under weak mutation and for arbitrary fitness landscapes, reversion rates decrease with time for any site that is involved in at least one epistatic interaction. Specifically, we prove that, at stationarity, the hazard function of the distribution of waiting times until reversion is strictly decreasing for any such site...
July 2016: Genetics
https://www.readbyqxmd.com/read/27193686/local-fitness-landscape-of-the-green-fluorescent-protein
#19
Karen S Sarkisyan, Dmitry A Bolotin, Margarita V Meer, Dinara R Usmanova, Alexander S Mishin, George V Sharonov, Dmitry N Ivankov, Nina G Bozhanova, Mikhail S Baranov, Onuralp Soylemez, Natalya S Bogatyreva, Peter K Vlasov, Evgeny S Egorov, Maria D Logacheva, Alexey S Kondrashov, Dmitry M Chudakov, Ekaterina V Putintseva, Ilgar Z Mamedov, Dan S Tawfik, Konstantin A Lukyanov, Fyodor A Kondrashov
Fitness landscapes depict how genotypes manifest at the phenotypic level and form the basis of our understanding of many areas of biology, yet their properties remain elusive. Previous studies have analysed specific genes, often using their function as a proxy for fitness, experimentally assessing the effect on function of single mutations and their combinations in a specific sequence or in different sequences. However, systematic high-throughput studies of the local fitness landscape of an entire protein have not yet been reported...
May 19, 2016: Nature
https://www.readbyqxmd.com/read/27170722/epistasis-between-antibiotic-resistance-mutations-and-genetic-background-shape-the-fitness-effect-of-resistance-across-species-of-pseudomonas
#20
T Vogwill, M Kojadinovic, R C MacLean
Antibiotic resistance often evolves by mutations at conserved sites in essential genes, resulting in parallel molecular evolution between divergent bacterial strains and species. Whether these resistance mutations are having parallel effects on fitness across bacterial taxa, however, is unclear. This is an important point to address, because the fitness effects of resistance mutations play a key role in the spread and maintenance of resistance in pathogen populations. We address this idea by measuring the fitness effect of a collection of rifampicin resistance mutations in the β subunit of RNA polymerase (rpoB) across eight strains that span the diversity of the genus Pseudomonas We find that almost 50% of rpoB mutations have background-dependent fitness costs, demonstrating that epistatic interactions between rpoB and the rest of the genome are common...
May 11, 2016: Proceedings. Biological Sciences
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