scholarly journals Differential paralog divergence modulates evolutionary outcomes in yeast

2016 ◽  
Author(s):  
Monica R. Sanchez ◽  
Aaron W. Miller ◽  
Ivan Liachko ◽  
Anna B. Sunshine ◽  
Bryony Lynch ◽  
...  
Keyword(s):  
Experimental Evolution ◽  
Relative Fitness ◽  
Controlled Environment ◽  
Wild Type ◽  
Evolutionary Potential ◽  
Fitness Effect ◽  
Sulfate Limitation ◽  
Show Evidence ◽  
Evolutionary Trajectories ◽  
Selective Forces

AbstractEvolutionary outcomes depend not only on the selective forces acting upon a species, but also on the genetic background. However, large timescales and uncertain historical selection pressures can make it difficult to discern such important background differences between species. Experimental evolution is one tool to compare evolutionary potential of known genotypes in a controlled environment. Here we utilized a highly reproducible evolutionary adaptation in Saccharomyces cerevisiae to investigate whether other yeast species would adopt similar evolutionary trajectories. We evolved populations of S. cerevisiae, S. paradoxus, S. mikatae, S. uvarum, and interspecific hybrids between S. uvarum and S. cerevisiae for ~200-500 generations in sulfate-limited continuous culture. Wild-type S. cerevisiae cultures invariably amplify the high affinity sulfate transporter gene, SUL1. However, while amplification of the SUL1 locus was detected in S. paradoxus and S. mikatae populations, S. uvarum cultures instead selected for amplification of the paralog, SUL2. We measured the relative fitness of strains bearing deletions and amplifications of both SUL genes from different species, confirming that, converse to S. cerevisiae, S. uvarum SUL2 contributes more to fitness in sulfate limitation than S. uvarum SUL1. By measuring the fitness and gene expression of chimeric promoter-ORF constructs, we were able to delineate the cause of this differential fitness effect primarily to the promoter of S. uvarum SUL1. Our data show evidence of differential sub-functionalization among the sulfur transporters across Saccharomyces species through recent changes in noncoding sequence. Furthermore, these results show a clear example of how such background differences due to paralog divergence can drive significant changes in evolutionary trajectories of eukaryotes.

scholarly journals Effects of intra-gene fitness interactions on the benefit of sexual recombination

2006 ◽  
Vol 34 (4) ◽  
pp. 560-561 ◽  
Author(s):  
R.A. Watson ◽  
D.M. Weinreich ◽  
J. Wakeley
Keyword(s):  
Nucleotide Sequence ◽  
Point Mutation ◽  
Sequence Space ◽  
Fitness Effect ◽  
Epistatic Interactions ◽  
Genetic Sequence ◽  
High Fitness ◽  
Sexual Recombination ◽  
Evolutionary Trajectories ◽  
Asexual Populations

Whereas spontaneous point mutation operates on nucleotides individually, sexual recombination manipulates the set of nucleotides within an allele as an essentially particulate unit. In principle, these two different scales of variation enable selection to follow fitness gradients in two different spaces: in nucleotide sequence space and allele sequence space respectively. Epistasis for fitness at these two scales, between nucleotides and between genes, may be qualitatively different and may significantly influence the advantage of mutation-based and recombination-based evolutionary trajectories respectively. We examine scenarios where the genetic sequence within a gene strongly influences the fitness effect of a mutation in that gene, whereas epistatic interactions between sites in different genes are weak or absent. We find that, in cases where beneficial alleles of a gene differ from one another at several nucleotide sites, sexual populations can exhibit enormous benefit compared with asexual populations: not only discovering fit genotypes faster than asexual populations, but also discovering high-fitness genotypes that are effectively not evolvable in asexual populations.

The effects of lestaurtinib (CEP701) and PKC412 on primary AML blasts: the induction of cytotoxicity varies with dependence on FLT3 signaling in both FLT3-mutated and wild-type cases

Blood ◽  
2006 ◽  
Vol 108 (10) ◽  
pp. 3494-3503 ◽  
Author(s):  
Steven Knapper ◽  
Kenneth I. Mills ◽  
Amanda F. Gilkes ◽  
Steve J. Austin ◽  
Val Walsh ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Wild Type ◽  
Mutation Status ◽  
Activating Mutations ◽  
Drug Concentrations ◽  
Flt3 Inhibitors ◽  
Show Evidence ◽  
Flt3 Expression ◽  
Molecular Therapeutic ◽  
Cytotoxic Responses

Abstract The receptor tyrosine kinase FLT3 is a promising molecular therapeutic target in acute myeloid leukemia (AML). Activating mutations of FLT3 are present in approximately one-third of patients, while many nonmutants show evidence of FLT3 activation, which appears to play a significant role in leukemogenesis. We studied the effects of lestaurtinib (CEP701) and PKC412, 2 small molecule inhibitors of FLT3, on 65 diagnostic AML blast samples. Both agents induced concentration-dependent cytotoxicity in most cases, although responses to PKC412 required higher drug concentrations. Cytotoxic responses were highly heterogeneous and were only weakly associated with FLT3 mutation status and FLT3 expression. Importantly, lestaurtinib induced cytotoxicity in a synergistic fashion with cytarabine, particularly in FLT3 mutant samples. Both lestaurtinib and PKC412 caused inhibition of FLT3 phosphorylation in all samples. Translation of FLT3 inhibition into cytotoxicity was influenced by the degree of residual FLT3 phosphorylation remaining and correlated with deactivation of STAT5 and MAP kinase. FLT3 mutant and wild-type cases both varied considerably in their dependence on FLT3 signaling for survival. These findings support the continued clinical assessment of FLT3 inhibitors in combination with cytotoxic chemotherapy: Entry to future clinical trials should include FLT3 wild-type patients and should remain unrestricted by FLT3 expression level.

scholarly journals Increase in Zucchini yellow mosaic virus Symptom Severity in Tolerant Zucchini Cultivars Is Related to a Point Mutation in P3 Protein and Is Associated with a Loss of Relative Fitness on Susceptible Plants

2003 ◽  
Vol 93 (12) ◽  
pp. 1478-1484 ◽  
Author(s):  
C. Desbiez ◽  
A. Gal-On ◽  
M. Girard ◽  
C. Wipf-Scheibel ◽  
H. Lecoq
Keyword(s):  
Mosaic Virus ◽  
Point Mutation ◽  
Zucchini Yellow Mosaic Virus ◽  
Genetic Load ◽  
Yellow Mosaic Virus ◽  
Relative Fitness ◽  
Interspecific Crosses ◽  
Mixed Infections ◽  
Wild Type ◽  
Sequence Comparisons

Zucchini yellow mosaic virus (ZYMV, Potyvirus) is a very damaging cucurbit virus worldwide. Interspecific crosses with resistant Cucurbita moschata have led to the release of “resistant” zucchini squash (C. pepo) F1 hybrids. However, although the resistance is almost complete in C. moschata, the commercial C. pepo hybrids are only tolerant. ZYMV evolution toward increased aggressiveness on tolerant hybrids was observed in the field and was obtained experimentally. Sequence comparisons and recombination experiments revealed that a point mutation in the P3 protein of ZYMV was enough to induce tolerance breaking. Competition experiments were performed between quasi-isogenic wild-type, and aggressive variants of ZYMV distinguished by monoclonal antibodies. The aggressive mutants were more fit than wild-type strains in mixed infections of tolerant zucchini, but they presented a drastic fitness loss in mixed infections of susceptible zucchini or melon. Thus, the ability to induce severe symptoms in tolerant zucchini is related to a genetic load in susceptible zucchini, but also on other susceptible hosts. This represents the first quantitative study of the fitness cost associated with tolerance breaking for a plant virus. Thus, although easily broken, the tolerance might prove durable in some conditions if the aggressive variants are counterselected in susceptible crops.

scholarly journals Somatic deficiency causes reproductive parasitism in a fungus

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexey A. Grum-Grzhimaylo ◽  
Eric Bastiaans ◽  
Joost van den Heuvel ◽  
Cristina Berenguer Millanes ◽  
Alfons J. M. Debets ◽  
...  
Keyword(s):  
Neurospora Crassa ◽  
Experimental Evolution ◽  
Evolutionary Dynamics ◽  
Genetic Load ◽  
Wild Type ◽  
Fusion Frequency ◽  
Somatic Fusion ◽  
Extensive Variation ◽  
Reproductive Parasitism ◽  
Multicellular Organisms

AbstractSome multicellular organisms can fuse because mergers potentially provide mutual benefits. However, experimental evolution in the fungus Neurospora crassa has demonstrated that free fusion of mycelia favours cheater lineages, but the mechanism and evolutionary dynamics of this exploitation are unknown. Here we show, paradoxically, that all convergently evolved cheater lineages have similar fusion deficiencies. These mutants are unable to initiate fusion but retain access to wild-type mycelia that fuse with them. This asymmetry reduces cheater-mutant contributions to somatic substrate-bound hyphal networks, but increases representation of their nuclei in the aerial reproductive hyphae. Cheaters only benefit when relatively rare and likely impose genetic load reminiscent of germline senescence. We show that the consequences of somatic fusion can be unequally distributed among fusion partners, with the passive non-fusing partner profiting more. We discuss how our findings may relate to the extensive variation in fusion frequency of fungi found in nature.

scholarly journals Evaluating the fitness of PA/I38T-substituted influenza A viruses with reduced baloxavir susceptibility in a competitive mixtures ferret model

2020 ◽  
Author(s):  
Leo YY Lee ◽  
Jie Zhou ◽  
Paulina Koszalka ◽  
Rebecca Frise ◽  
Rubaiyea Farrukee ◽  
...  
Keyword(s):  
Influenza A ◽  
Relative Fitness ◽  
Replication Capacity ◽  
Wild Type ◽  
Influenza A Viruses ◽  
Widespread Occurrence ◽  
Host Fitness ◽  
Recombinant Viruses ◽  
Risk Patients ◽  
Virus Isolates

AbstractBaloxavir is approved in several countries for the treatment of uncomplicated influenza in otherwise-healthy and high-risk patients. Treatment-emergent viruses with reduced susceptibility to baloxavir have been detected in clinical trials, but the likelihood of widespread occurrence depends on replication capacity and onward transmission. We evaluated the fitness of A/H3N2 and A/H1N1pdm09 viruses with the polymerase acidic I38T-variant conferring reduced susceptibility to baloxavir relative to wild-type (WT) viruses, using a competitive mixture ferret model, recombinant viruses and patient-derived virus isolates. The A/H3N2 I38T virus showed a reduction in within-host fitness but comparable between-host fitness to the WT virus, while the A/H1N1pdm09 I38T virus had broadly similar within-host fitness but substantially lower between-host fitness. Although I38T viruses replicate and transmit between ferrets, our data suggest that viruses with this amino acid substitution have lower fitness relative to WT and this relative fitness cost was greater in A/H1N1pdm09 viruses than in A/H3N2 viruses.

scholarly journals Chance, contingency, and necessity in the experimental evolution of ancestral proteins

2020 ◽  
Author(s):  
Victoria Cochran Xie ◽  
Jinyue Pu ◽  
Brian P.H. Metzger ◽  
Joseph W. Thornton ◽  
Bryan C. Dickinson
Keyword(s):  
Protein Evolution ◽  
Experimental Evolution ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Sequence Evolution ◽  
Protein Protein Interaction ◽  
Evolutionary Trajectories ◽  
Historical Moment ◽  
Related Proteins ◽  
Ancestral Protein

SUMMARYThe extent to which chance and contingency shaped the sequence outcomes of protein evolution is largely unknown. To directly characterize the causes and consequences of chance and contingency, we combined directed evolution with ancestral protein reconstruction. By repeatedly selecting a phylogenetic series of ancestral proteins in the B-cell lymphoma-2 family to evolve the same protein-protein interaction specificities that existed during history, we show that contingency and chance interact to make sequence evolution almost entirely unpredictable over the timescale of metazoan evolution. At any historical moment, multiple sets of mutations can alter or maintain specificity, and chance decides which ones occur. Contingency arises because historical sequence substitutions epistatically altered which mutations are compatible with new or ancestral functions. Evolutionary trajectories launched from different ancestors therefore lead to dramatically different outcomes over phylogenetic time, with virtually no mutations occurring repeatedly in distantly related proteins, even under identical selection conditions.

scholarly journals Similarities and differences between IL11 and IL11RA1 knockout mice for lung fibro-inflammation, fertility and craniosynostosis

2020 ◽  
Author(s):  
Benjamin Ng ◽  
Anissa A. Widjaja ◽  
Sivakumar Viswanathan ◽  
Jinrui Dong ◽  
Sonia P. Chothani ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Lung Fibroblasts ◽  
Loss Of Function ◽  
Wild Type ◽  
Reduced Body ◽  
Body Weights ◽  
Show Evidence ◽  
Similarities And Differences ◽  
The Impact

AbstractGenetic loss of function (LOF) in IL11RA infers IL11 signaling as important for fertility, fibrosis, inflammation and craniosynostosis. The impact of genetic LOF in IL11 has not been characterized. We generated IL11-knockout (Il11-/-) mice, which are born in normal Mendelian ratios, have normal hematological profiles and are protected from bleomycin-induced lung fibro-inflammation. Noticeably, baseline IL6 levels in the lungs of Il11-/- mice are lower than those of wild-type mice and are not induced by bleomycin damage, placing IL11 upstream of IL6. Lung fibroblasts from Il11-/- mice are resistant to pro-fibrotic stimulation and show evidence of reduced autocrine IL11 activity. Il11-/- female mice are infertile. Unlike Il11ra1-/- mice, Il11-/- mice do not have a craniosynostosis-like phenotype and exhibit mildly reduced body weights. These data highlight similarities and differences between LOF in IL11 or IL11RA while establishing further the role of IL11 signaling in fibrosis and stromal inflammation.

scholarly journals Local adaptation mediated niche expansion in correlation with genetic richness

2021 ◽  
Author(s):  
Masaomi Kurokawa ◽  
Issei Nishimura ◽  
Bei-Wen YING
Keyword(s):  
Escherichia Coli ◽  
Local Adaptation ◽  
High Throughput ◽  
Experimental Evolution ◽  
Environmental Gradient ◽  
Growth Curves ◽  
Quantitative Relationship ◽  
Central Issue ◽  
Wild Type ◽  
Niche Expansion

As a central issue in evolution and ecology, the quantitative relationship among the genome, adaptation and the niche was investigated. Local adaptation of five Escherichia coli strains carrying either the wild-type genome or reduced genomes was achieved by experimental evolution. A high-throughput fitness assay of the ancestor and evolved populations across an environmental gradient of eight niches resulted in a total of 80 fitness curves generated from 2,220 growth curves. Further analyses showed that the increases in both local adaptiveness and niche broadness were negatively correlated with genetic richness. Local adaptation caused common niche expansion, whereas niche expansion for generality or speciality was decided by genetic richness. The order of the mutations accumulated stepwise was correlated with the magnitude of the fitness increase attributed to mutation accumulation. Pre-adaptation probably participated in coordination among genetic richness, local adaptation and niche expansion.

scholarly journals Maximum likelihood estimation of fitness components in experimental evolution

2018 ◽  
Author(s):  
Jingxian Liu ◽  
Jackson Champer ◽  
Chen Liu ◽  
Joan Chung ◽  
Riona Reeves ◽  
...  
Keyword(s):  
Maximum Likelihood ◽  
Experimental Evolution ◽  
Evolutionary Dynamics ◽  
Likelihood Estimation ◽  
Loss Of Function ◽  
Wild Type ◽  
Fitness Components ◽  
Linked Gene ◽  
Males And Females

AbstractEstimating fitness differences between allelic variants is a central goal of experimental evolution. Current methods for inferring selection from allele frequency time series typically assume that evolutionary dynamics at the locus of interest can be described by a fixed selection coefficient. However, fitness is an aggregate of several components including mating success, fecundity, and viability, and distinguishing between these components could be critical in many scenarios. Here we develop a flexible maximum likelihood framework that can disentangle different components of fitness and estimate them individually in males and females from genotype frequency data. As a proof-of-principle, we apply our method to experimentally-evolved cage populations of Drosophila melanogaster, in which we tracked the relative frequencies of a loss-of-function and wild-type allele of yellow. This X-linked gene produces a recessive yellow phenotype when disrupted and is involved in male courtship ability. We find that the fitness costs of the yellow phenotype take the form of substantially reduced mating preference of wild-type females for yellow males, together with a modest reduction in the viability of yellow males and females. Our framework should be generally applicable to situations where it is important to quantify fitness components of specific genetic variants, including quantitative characterization of the population dynamics of CRISPR gene drives.

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