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1.
Commun Biol ; 4(1): 536, 2021 05 06.
Article in English | MEDLINE | ID: mdl-33958697

ABSTRACT

For natural selection to operate there must exist heritable variation among individuals that affects their survival and reproduction. Among free-living microbes, where differences in growth rates largely define selection intensities, competitive exclusion is common. However, among surface attached communities, these dynamics become less predictable. If extreme circumstances were to dictate that a surface population is immortal and all offspring must emigrate, the offspring would be unable to contribute to the composition of the population. Meanwhile, the immortals, regardless of reproductive capacity, would remain unchanged in relative abundance. The normal cycle of birth, death, and competitive exclusion would be broken. We tested whether conditions required to set up this idealized scenario can be approximated in a microbial biofilm. Using two differentially-reproducing strains of Shewanella oneidensis grown on an anode as the sole terminal electron acceptor - a system in which metabolism is obligately tied to surface attachment - we found that selection against a slow-growing competitor is drastically reduced. This work furthers understanding of natural selection dynamics in sessile microbial communities, and provides a framework for designing stable microbial communities for industrial and experimental applications.


Subject(s)
Bioelectric Energy Sources/microbiology , Biofilms/growth & development , Shewanella/growth & development , Electrodes , Electron Transport , Surface Properties
2.
Ecology ; 101(9): e03098, 2020 09.
Article in English | MEDLINE | ID: mdl-32443176

ABSTRACT

The ability of random environmental variation to stabilize competitor coexistence was pointed out long ago and, in recent years, has received considerable attention. Analyses have focused on variations in the log abundances of species, with mean logarithmic growth rates when rare, Er , used as metrics for persistence. However, invasion probabilities and the times to extinction are not single-valued functions of Er and, in some cases, decrease as Er increases. Here, we present a synthesis of stochasticity-induced stabilization (SIS) phenomena based on the ratio between the expected arithmetic growth µ and its variance g . When the diffusion approximation holds, explicit formulas for invasion probabilities and persistence times are single-valued, monotonic functions of µ/g . The storage effect in the lottery model, together with other well-known examples drawn from population genetics, microbiology, and ecology (including discrete and continuous dynamics, with overlapping and non-overlapping generations), are placed together, reviewed, and explained within this new, transparent theoretical framework. We also clarify the relationships between life-history strategies and SIS, and study the dynamics of extinction when SIS fails.


Subject(s)
Ecology , Genetics, Population , Models, Biological , Population Dynamics , Probability , Stochastic Processes
3.
Toxicon ; 178: 92-99, 2020 Apr 30.
Article in English | MEDLINE | ID: mdl-32135198

ABSTRACT

Opossums in the clade Didelphini are well known to be resistant to snake venom due to endogenous circulating inhibitors which target metalloproteinases and phospholipases. However, the mechanisms through which these opossums cope with a variety of other damaging venom proteins are unknown. A protein involved in blood clotting (von Willebrand Factor) has been found to have undergone rapid adaptive evolution in venom-resistant opossums. This protein is a known target for a subset of snake venom C-type lectins (CTLs), which bind it and then induce it to bind platelets, causing hemostatic disruption. Several amino acid changes in vWF unique to these opossums could explain their resistance; however, experimental evidence that these changes disrupt venom CTL binding was lacking. We used platelet aggregation assays to quantify resistance to a venom-induced platelet response in two species of venom-resistant opossums (Didelphis virginiana, Didelphis aurita), and one venom-sensitive opossum (Monodelphis domestica). We found that all three species have lost nearly all their aggregation response to the venom CTLs tested. Using washed platelet assays we showed that this loss of aggregation response is not due to inhibitors in the plasma, but rather to the failure of either vWF or platelets (or both) to respond to venom CTLs. These results demonstrate the potential adaptive function of a trait previously shown to be evolving under positive selection. Surprisingly, these findings also expand the list of potentially venom tolerant species to include Monodelphis domestica and suggest that an ecological relationship between opossums and vipers may be a broader driver of adaptive evolution across South American marsupials than previously thought.


Subject(s)
Adaptation, Physiological/physiology , Didelphis/physiology , Snake Venoms/toxicity , von Willebrand Factor/metabolism , Animals , Blood Platelets/metabolism , Lectins, C-Type/metabolism , Metalloproteases/metabolism , Platelet Aggregation , Snake Venoms/chemistry , Snake Venoms/metabolism , South America
4.
Toxicon, v. 178, p. 92-99, abr. 2020
Article in English | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-2966

ABSTRACT

Opossums in the clade Didelphini are well known to be resistant to snake venom due to endogenous circulating inhibitors which target metalloproteinases and phospholipases. However, the mechanisms through which these opossums cope with a variety of other damaging venom proteins are unknown. A protein involved in blood clotting (von Willebrand Factor) has been found to have undergone rapid adaptive evolution in venom-resistant opossums. This protein is a known target for a subset of snake venom C-type lectins (CTLs), which bind it and then induce it to bind platelets, causing hemostatic disruption. Several amino acid changes in vWF unique to these opossums could explain their resistance; however, experimental evidence that these changes disrupt venom CTL binding was lacking. We used platelet aggregation assays to quantify resistance to a venom-induced platelet response in two species of venom-resistant opossums (Didelphis virginiana, Didelphis aurita), and one venom-sensitive opossum (Monodelphis domestica). We found that all three species have lost nearly all their aggregation response to the venom CTLs tested. Using washed platelet assays we showed that this loss of aggregation response is not due to inhibitors in the plasma, but rather to the failure of either vWF or platelets (or both) to respond to venom CTLs. These results demonstrate the potential adaptive function of a trait previously shown to be evolving under positive selection. Surprisingly, these findings also expand the list of potentially venom tolerant species to include Monodelphis domestica and suggest that an ecological relationship between opossums and vipers may be a broader driver of adaptive evolution across South American marsupials than previously thought

5.
Toxicon ; 178: 92-99, 2020.
Article in English | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: but-ib17522

ABSTRACT

Opossums in the clade Didelphini are well known to be resistant to snake venom due to endogenous circulating inhibitors which target metalloproteinases and phospholipases. However, the mechanisms through which these opossums cope with a variety of other damaging venom proteins are unknown. A protein involved in blood clotting (von Willebrand Factor) has been found to have undergone rapid adaptive evolution in venom-resistant opossums. This protein is a known target for a subset of snake venom C-type lectins (CTLs), which bind it and then induce it to bind platelets, causing hemostatic disruption. Several amino acid changes in vWF unique to these opossums could explain their resistance; however, experimental evidence that these changes disrupt venom CTL binding was lacking. We used platelet aggregation assays to quantify resistance to a venom-induced platelet response in two species of venom-resistant opossums (Didelphis virginiana, Didelphis aurita), and one venom-sensitive opossum (Monodelphis domestica). We found that all three species have lost nearly all their aggregation response to the venom CTLs tested. Using washed platelet assays we showed that this loss of aggregation response is not due to inhibitors in the plasma, but rather to the failure of either vWF or platelets (or both) to respond to venom CTLs. These results demonstrate the potential adaptive function of a trait previously shown to be evolving under positive selection. Surprisingly, these findings also expand the list of potentially venom tolerant species to include Monodelphis domestica and suggest that an ecological relationship between opossums and vipers may be a broader driver of adaptive evolution across South American marsupials than previously thought

6.
Mol Biol Evol ; 36(5): 890-907, 2019 05 01.
Article in English | MEDLINE | ID: mdl-30657938

ABSTRACT

For nearly a century adaptive landscapes have provided overviews of the evolutionary process and yet they remain metaphors. We redefine adaptive landscapes in terms of biological processes rather than descriptive phenomenology. We focus on the underlying mechanisms that generate emergent properties such as epistasis, dominance, trade-offs and adaptive peaks. We illustrate the utility of landscapes in predicting the course of adaptation and the distribution of fitness effects. We abandon aged arguments concerning landscape ruggedness in favor of empirically determining landscape architecture. In so doing, we transform the landscape metaphor into a scientific framework within which causal hypotheses can be tested.


Subject(s)
Adaptation, Biological , Biological Evolution , Models, Genetic , 3-Isopropylmalate Dehydrogenase/genetics , Animals , Chemotaxis , Escherichia coli , Genetic Fitness , Genotype , Lac Operon , Lac Repressors/genetics , Methanol/metabolism , Opsins/genetics , Synthetic Biology
7.
Theor Popul Biol ; 124: 16-30, 2018 12.
Article in English | MEDLINE | ID: mdl-30208298

ABSTRACT

I analyze the joint impact of directional and fluctuating selection with reversible mutation in finite bi-allelic haploid populations using diffusion approximations of the Moran and chemostat models. Results differ dramatically from those of the classic Wright-Fisher diffusion. There, a strong dispersive effect attributable to fluctuating selection dissipates nascent polymorphisms promoted by a relatively weak emergent frequency dependent selective effect. The dispersive effect in the Moran diffusion with fluctuations every birth-death event is trivial. The same frequency dependent selective effect now dominates and polymorphism is promoted. The dispersive effect in the chemostat diffusion with fluctuations every generation is identical to that in the Wright-Fisher diffusion. Nevertheless, polymorphism is again promoted because the emergent frequency dependent effect is doubled, an effect attributable to geometric reproduction within generations. Fluctuating selection in the Moran and chemostat diffusions can also promote bi-allelic polymorphisms when one allele confers a net benefit. Rapid fluctuations within generations are highly effective at promoting polymorphism in large populations. The bi-allelic distribution is approximately Gaussian but becomes uniform and then U-shaped as the frequency of environmental fluctuations decreases to once a generation and then once every multiple generations. Trade-offs (negative correlations in fitness) help promote polymorphisms but are not essential. In all three models the frequency dependent effect raises the probability of ultimate fixation of new alleles, but less effectively in the Wright-Fisher diffusion. Individual-based forward simulations confirm the calculations.


Subject(s)
Genetics, Population/methods , Models, Genetic , Polymorphism, Genetic , Selection, Genetic , Alleles , Computer Simulation , Gene Frequency , Haploidy , Mutation , Probability
8.
Genetics ; 205(3): 1271-1283, 2017 03.
Article in English | MEDLINE | ID: mdl-28108586

ABSTRACT

Contrary to classical population genetics theory, experiments demonstrate that fluctuating selection can protect a haploid polymorphism in the absence of frequency dependent effects on fitness. Using forward simulations with the Moran model, we confirm our analytical results showing that a fluctuating selection regime, with a mean selection coefficient of zero, promotes polymorphism. We find that increases in heterozygosity over neutral expectations are especially pronounced when fluctuations are rapid, mutation is weak, the population size is large, and the variance in selection is big. Lowering the frequency of fluctuations makes selection more directional, and so heterozygosity declines. We also show that fluctuating selection raises dn /ds ratios for polymorphism, not only by sweeping selected alleles into the population, but also by purging the neutral variants of selected alleles as they undergo repeated bottlenecks. Our analysis shows that randomly fluctuating selection increases the rate of evolution by increasing the probability of fixation. The impact is especially noticeable when the selection is strong and mutation is weak. Simulations show the increase in the rate of evolution declines as the rate of new mutations entering the population increases, an effect attributable to clonal interference. Intriguingly, fluctuating selection increases the dn /ds ratios for divergence more than for polymorphism, a pattern commonly seen in comparative genomics. Our model, which extends the classical neutral model of molecular evolution by incorporating random fluctuations in selection, accommodates a wide variety of observations, both neutral and selected, with economy.


Subject(s)
Evolution, Molecular , Models, Genetic , Selection, Genetic , Gene Frequency , Haploidy , Heterozygote , Homozygote , Polymorphism, Genetic
9.
Elife ; 52016 10 03.
Article in English | MEDLINE | ID: mdl-27692064

ABSTRACT

We report the evolution of a phenotypically plastic behavior that circumvents the hardwired trade-off that exists when resources are partitioned between growth and motility in Escherichia coli. We propagated cultures in a cyclical environment, alternating between growth up to carrying capacity and selection for chemotaxis. Initial adaptations boosted overall swimming speed at the expense of growth. The effect of the trade-off was subsequently eased through a change in behavior; while individual cells reduced motility during exponential growth, the faction of the population that was motile increased as the carrying capacity was approached. This plastic behavior was produced by a single amino acid replacement in FliA, a regulatory protein central to the chemotaxis network. Our results illustrate how phenotypic plasticity potentiates evolvability by opening up new regions of the adaptive landscape.


Subject(s)
Adaptation, Physiological , Chemotaxis , Escherichia coli/physiology , Phenotype , Escherichia coli/growth & development , Sigma Factor/genetics , Sigma Factor/metabolism
10.
J Am Chem Soc ; 138(3): 1046-56, 2016 Jan 27.
Article in English | MEDLINE | ID: mdl-26736133

ABSTRACT

Catalytic promiscuity is a useful, but accidental, enzyme property, so finding catalytically promiscuous enzymes in nature is inefficient. Some ancestral enzymes were branch points in the evolution of new enzymes and are hypothesized to have been promiscuous. To test the hypothesis that ancestral enzymes were more promiscuous than their modern descendants, we reconstructed ancestral enzymes at four branch points in the divergence hydroxynitrile lyases (HNL's) from esterases ∼ 100 million years ago. Both enzyme types are α/ß-hydrolase-fold enzymes and have the same catalytic triad, but differ in reaction type and mechanism. Esterases catalyze hydrolysis via an acyl enzyme intermediate, while lyases catalyze an elimination without an intermediate. Screening ancestral enzymes and their modern descendants with six esterase substrates and six lyase substrates found higher catalytic promiscuity among the ancestral enzymes (P < 0.01). Ancestral esterases were more likely to catalyze a lyase reaction than modern esterases, and the ancestral HNL was more likely to catalyze ester hydrolysis than modern HNL's. One ancestral enzyme (HNL1) along the path from esterase to hydroxynitrile lyases was especially promiscuous and catalyzed both hydrolysis and lyase reactions with many substrates. A broader screen tested mechanistically related reactions that were not selected for by evolution: decarboxylation, Michael addition, γ-lactam hydrolysis and 1,5-diketone hydrolysis. The ancestral enzymes were more promiscuous than their modern descendants (P = 0.04). Thus, these reconstructed ancestral enzymes are catalytically promiscuous, but HNL1 is especially so.


Subject(s)
Aldehyde-Lyases/metabolism , Biocatalysis , Esterases/metabolism , Aldehyde-Lyases/chemistry , Carboxylic Acids/chemistry , Carboxylic Acids/metabolism , Esterases/chemistry , Esters/chemistry , Esters/metabolism , Hydrogen Cyanide/chemistry , Hydrogen Cyanide/metabolism , Hydrolysis , Nitriles/chemistry , Nitriles/metabolism
11.
Mol Biol Evol ; 33(4): 971-9, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26681154

ABSTRACT

The means by which superfamilies of specialized enzymes arise by gene duplication and functional divergence are poorly understood. The escape from adaptive conflict hypothesis, which posits multiple copies of a gene encoding a primitive inefficient and highly promiscuous generalist ancestor, receives support from experiments showing that resurrected ancestral enzymes are indeed more substrate-promiscuous than their modern descendants. Here, we provide evidence in support of an alternative model, the innovation-amplification-divergence hypothesis, which posits a single-copied ancestor as efficient and specific as any modern enzyme. We argue that the catalytic mechanisms of plant esterases and descendent acetone cyanohydrin lyases are incompatible with each other (e.g., the reactive substrate carbonyl must bind in opposite orientations in the active site). We then show that resurrected ancestral plant esterases are as catalytically specific as modern esterases, that the ancestor of modern acetone cyanohydrin lyases was itself only very weakly promiscuous, and that improvements in lyase activity came at the expense of esterase activity. These observations support the innovation-amplification-divergence hypothesis, in which an ancestor gains a weak promiscuous activity that is improved by selection at the expense of the ancestral activity, and not the escape from adaptive conflict in which an inefficient generalist ancestral enzyme steadily loses promiscuity throughout the transition to a highly active specialized modern enzyme.


Subject(s)
Evolution, Molecular , Genetic Variation , Hydrolases/genetics , Phylogeny , Aldehyde-Lyases/genetics , Catalysis , Catalytic Domain , Gene Duplication
12.
J Theor Biol ; 380: 123-33, 2015 Sep 07.
Article in English | MEDLINE | ID: mdl-25983046

ABSTRACT

Typical mutation-selection models assume well-mixed populations, but dispersal and migration within many natural populations is spatially limited. Such limitations can lead to enhanced variation among locations as different types become clustered in different places. Such clustering weakens competition between unlike types relative to competition between like types; thus, the rate by which a fitter type displaces an inferior competitor can be affected by the spatial scale of movement. In this paper, we use a birth-death model to show that limited migration can affect asexual populations by creating competitive refugia. We use a moment closure approach to show that as population structure is introduced by limiting migration, the equilibrial frequency of deleterious mutants increases. We support and extend the model through stochastic simulation, and we use a spatially explicit cellular automaton approach to corroborate the results. We discuss the implications of these results for standing variation in structured populations and adaptive valley crossing in Wright's "shifting balance" process.


Subject(s)
Mutation , Selection, Genetic , Models, Theoretical , Stochastic Processes
13.
Toxicon ; 99: 68-72, 2015 Jun 01.
Article in English | MEDLINE | ID: mdl-25796346

ABSTRACT

Honey badgers (Mellivora capensis) prey upon and survive bites from venomous snakes (Family: Elapidae), but the molecular basis of their venom resistance is unknown. The muscular nicotinic cholinergic receptor (nAChR), targeted by snake α-neurotoxins, has evolved in some venom-resistant mammals to no longer bind these toxins. Through phylogenetic analysis of mammalian nAChR sequences, we show that honey badgers, hedgehogs, and pigs have independently acquired functionally equivalent amino acid replacements in the toxin-binding site of this receptor. These convergent amino acid changes impede toxin binding by introducing a positively charged amino acid in place of an uncharged aromatic residue. In venom-resistant mongooses, different replacements at these same sites are glycosylated, which is thought to disrupt binding through steric effects. Thus, it appears that resistance to snake venom α-neurotoxin has evolved at least four times among mammals through two distinct biochemical mechanisms operating at the same sites on the same receptor.


Subject(s)
Elapid Venoms/antagonists & inhibitors , Elapidae/physiology , Evolution, Molecular , Models, Molecular , Mustelidae/physiology , Receptors, Nicotinic/genetics , Snake Bites/veterinary , Animals , Animals, Zoo/blood , Animals, Zoo/genetics , Animals, Zoo/physiology , Binding Sites , Databases, Protein , Drug Resistance, Multiple , Elapid Venoms/chemistry , Elapid Venoms/toxicity , Ligands , Mustelidae/blood , Mustelidae/genetics , Nerve Tissue Proteins/chemistry , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neurotoxins/antagonists & inhibitors , Neurotoxins/chemistry , Neurotoxins/toxicity , Phylogeny , Predatory Behavior , Protein Conformation , Receptors, Nicotinic/chemistry , Receptors, Nicotinic/metabolism , Snake Bites/metabolism , Snake Bites/physiopathology
14.
Chembiochem ; 15(8): 1145-53, 2014 May 26.
Article in English | MEDLINE | ID: mdl-24797066

ABSTRACT

An active site lysine essential to catalysis in isocitrate dehydrogenase (IDH) is absent from related enzymes. As all family members catalyze the same oxidative ß-decarboxylation at the (2R)-malate core common to their substrates, it seems odd that an amino acid essential to one is not found in all. Ordinarily, hydride transfer to a nicotinamide C4 neutralizes the positive charge at N1 directly. In IDH, the negatively charged C4-carboxylate of isocitrate stabilizes the ground state positive charge on the adjacent nicotinamide N1, opposing hydride transfer. The critical lysine is poised to stabilize-and perhaps even protonate-an oxyanion formed on the nicotinamide 3-carboxamide, thereby enabling the hydride to be transferred while the positive charge at N1 is maintained. IDH might catalyze the same overall reaction as other family members, but dehydrogenation proceeds through a distinct, though related, transition state. Partial activation of lysine mutants by K(+) and NH4 (+) represents a throwback to the primordial state of the first promiscuous substrate family member.


Subject(s)
Escherichia coli/enzymology , Isocitrate Dehydrogenase/chemistry , Isocitrate Dehydrogenase/metabolism , Lysine/metabolism , Catalytic Domain/genetics , Crystallography, X-Ray , Isocitrate Dehydrogenase/genetics , Isocitrate Dehydrogenase/isolation & purification , Kinetics , Lysine/genetics , Models, Molecular , Molecular Structure
15.
J Bacteriol ; 195(24): 5479-86, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24097946

ABSTRACT

Riboflavin (vitamin B2) is the precursor of flavin mononucleotide and flavin adenine dinucleotide, which are cofactors essential for a host of intracellular redox reactions. Microorganisms synthesize flavins de novo to fulfill nutritional requirements, but it is becoming increasingly clear that flavins play a wider role in cellular physiology than was previously appreciated. Flavins mediate diverse processes beyond the cytoplasmic membrane, including iron acquisition, extracellular respiration, and interspecies interactions. While investigating the regulation of flavin electron shuttle biosynthesis in the Gram-negative gammaproteobacterium Shewanella oneidensis, we discovered that a riboflavin biosynthetic gene (ribBA) annotated as encoding a bifunctional 3,4-dihydroxy-2-butanone 4-phosphate (DHBP) synthase/GTP cyclohydrolase II does not possess both functions. The novel gene, renamed ribBX here, encodes an amino-terminal DHBP synthase domain. The carboxy-terminal end of RibBX not only lacks GTP cyclohydrolase II activity but also has evolved a different function altogether in S. oneidensis, regulating the activity of the DHBP synthase domain. Phylogenetic analysis revealed that the misannotation of ribBX as ribBA is rampant throughout the phylum Proteobacteria (40% of 2,173 annotated ribBA genes) and that ribBX emerged early in the evolution of this group of microorganisms. We examined the functionality of representative ribBX genes from Beta-, Gamma-, and Epsilonproteobacteria and found that, consistent with sequence-based predictions, the encoded GTP cyclohydrolase II domains lack catalytic activity. The persistence of ribBX in the genomes of so many phylogenetically divergent bacterial species lends weight to the argument that ribBX has evolved a function which lends a selective advantage to the host.


Subject(s)
Biosynthetic Pathways/genetics , Intramolecular Transferases/genetics , Intramolecular Transferases/metabolism , Proteobacteria/enzymology , Proteobacteria/genetics , Riboflavin/biosynthesis , Evolution, Molecular , Phylogeny , Protein Structure, Tertiary , Sequence Homology, Amino Acid
16.
Proc Natl Acad Sci U S A ; 110(42): 16945-50, 2013 Oct 15.
Article in English | MEDLINE | ID: mdl-24077262

ABSTRACT

Existing theory predicts competitors (species or genetic clones) cannot coexist in a fluctuating environment unless relative fitness is negatively frequency-dependent (relative fitness declines as the frequency of a competitor increases). We develop simple theory to show coexistence does not require frequency-dependent selection, and we confirm this prediction by direct experiment. The conditions for coexistence in a fluctuating environment are precisely the same as those for coexistence in a spatially variable environment, conditions that arise naturally whenever population abundances are bounded. Simulations show the likelihood of coexistence increases with environmental uncertainty. The capacity of temporally variable environments to maintain biological diversity is far broader than generally envisaged.


Subject(s)
Computer Simulation , Ecosystem , Escherichia coli/physiology , Models, Biological
17.
PLoS Genet ; 6(10): e1001162, 2010 Oct 21.
Article in English | MEDLINE | ID: mdl-20975933

ABSTRACT

The functional effects of most amino acid replacements accumulated during molecular evolution are unknown, because most are not observed naturally and the possible combinations are too numerous. We created 168 single mutations in wild-type Escherichia coli isopropymalate dehydrogenase (IMDH) that match the differences found in wild-type Pseudomonas aeruginosa IMDH. 104 mutant enzymes performed similarly to E. coli wild-type IMDH, one was functionally enhanced, and 63 were functionally compromised. The transition from E. coli IMDH, or an ancestral form, to the functional wild-type P. aeruginosa IMDH requires extensive epistasis to ameliorate the combined effects of the deleterious mutations. This result stands in marked contrast with a basic assumption of molecular phylogenetics, that sites in sequences evolve independently of each other. Residues that affect function are scattered haphazardly throughout the IMDH structure. We screened for compensatory mutations at three sites, all of which lie near the active site and all of which are among the least active mutants. No compensatory mutations were found at two sites indicating that a single site may engage in compound epistatic interactions. One complete and three partial compensatory mutations of the third site are remote and lie in a different domain. This demonstrates that epistatic interactions can occur between distant (>20Å) sites. Phylogenetic analysis shows that incompatible mutations were fixed in different lineages.


Subject(s)
Amino Acid Substitution/genetics , Epistasis, Genetic/genetics , Evolution, Molecular , Mutation , 3-Isopropylmalate Dehydrogenase/classification , 3-Isopropylmalate Dehydrogenase/genetics , 3-Isopropylmalate Dehydrogenase/metabolism , Amino Acid Sequence , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Base Sequence , Binding Sites/genetics , Escherichia coli/genetics , Escherichia coli Proteins/chemistry , Escherichia coli Proteins/genetics , Escherichia coli Proteins/metabolism , Kinetics , Models, Molecular , Molecular Sequence Data , Mutagenesis, Site-Directed , NAD/metabolism , Phylogeny , Protein Structure, Tertiary , Pseudomonas aeruginosa/genetics , Sequence Homology, Amino Acid
18.
J Mol Evol ; 71(4): 241-9, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20809353

ABSTRACT

The testis-specific gene Jingwei (jgw) is a newly evolved short-chain dehydrogenase/reductase in Drosophila. Preliminary substrate screening indicated that JGW prefers long-chain primary alcohols as substrates, including several exotic alcohols such as farnesol and geraniol. Using steady-state kinetics analyses and molecular docking, we not only confirmed JGW's substrate specificity, but also demonstrated that the new enzymatic activities of JGW evolved extensively after exon-shuffling from a preexisting enzyme. Analysis of JGW orthologs in sister species shows that subsequent evolutionary changes following the birth of JGW altered substrate specificities and enzyme stabilities. Our results lend support to a general mechanism for the evolution of a new enzyme, in which catalytic chemistry evolves first followed by diversification of substrate utilization.


Subject(s)
Drosophila Proteins/genetics , Drosophila melanogaster/enzymology , Drosophila melanogaster/genetics , Evolution, Molecular , Fatty Acid Synthases/genetics , Fatty Acid Synthases/metabolism , Mutant Chimeric Proteins/genetics , NADH, NADPH Oxidoreductases/genetics , NADH, NADPH Oxidoreductases/metabolism , Testis/enzymology , Alcohol Dehydrogenase/chemistry , Alcohol Dehydrogenase/genetics , Amino Acid Substitution/genetics , Animals , Biocatalysis/drug effects , Catalytic Domain , Computer Simulation , Detergents/pharmacology , Drosophila Proteins/chemistry , Enzyme Stability/drug effects , Fatty Acid Synthases/chemistry , Hydrogen-Ion Concentration/drug effects , Male , Mutant Chimeric Proteins/chemistry , NADH, NADPH Oxidoreductases/chemistry , Organ Specificity/drug effects , Organ Specificity/genetics , Protein Structure, Tertiary , Structural Homology, Protein , Substrate Specificity/drug effects
19.
Philos Trans R Soc Lond B Biol Sci ; 365(1552): 2503-13, 2010 Aug 27.
Article in English | MEDLINE | ID: mdl-20643740

ABSTRACT

Understanding pathogen infectivity and virulence requires combining insights from epidemiology, ecology, evolution and genetics. Although theoretical work in these fields has identified population structure as important for pathogen life-history evolution, experimental tests are scarce. Here, we explore the impact of population structure on life-history evolution in phage T4, a viral pathogen of Escherichia coli. The host-pathogen system is propagated as a metapopulation in which migration between subpopulations is either spatially restricted or unrestricted. Restricted migration favours pathogens with low infectivity and low virulence. Unrestricted migration favours pathogens that enter and exit their hosts quickly, although they are less productive owing to rapid extirpation of the host population. The rise of such 'rapacious' phage produces a 'tragedy of the commons', in which better competitors lower productivity. We have now identified a genetic basis for a rapacious life history. Mutations at a single locus (rI) cause increased virulence and are sufficient to account for a negative relationship between phage competitive ability and productivity. A higher frequency of rI mutants under unrestricted migration signifies the evolution of rapaciousness in this treatment. Conversely, spatially restricted migration favours a more 'prudent' pathogen strategy, in which the tragedy of the commons is averted. As our results illustrate, profound epidemiological and ecological consequences of life-history evolution in a pathogen can have a simple genetic cause.


Subject(s)
Bacteriophage T4/genetics , Bacteriophage T4/pathogenicity , Escherichia coli/virology , Evolution, Molecular , Host-Pathogen Interactions , Movement , Virus Internalization , Adsorption , Models, Biological , Population Dynamics , Spectrophotometry , Virulence
20.
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