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Results for “selection pressure”

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At least 19 recordsLinked to original sources

PubMed2004

Representation of mutation pressure and selection pressure by PAM matrices.

This paper analyses the relationship between the mutation data matrix 1PAM/PET91, representing the effect of both mutation and selection pressures exerted on 16130 homologous proteins of different organisms, and a mutation probability matrix (1PAM/MPM) representing the effect of pure mutation pressure on protein coding of the Borrelia burgdorferi genome. The 1PAM/PMP matrix was derived with the help of computer simulations, which used empirical nucleotide substitution rates found for the B. burgdorferi genome. Here, it is shown that the frequency of amino acid occurrence is strongly related to their effective survival time. We found that the shorter the turnover time of an amino acid under pure mutation pressure, the lower its fraction in the proteins coded by the genome and the more protected by selection pressure is its position in proteins. Results of analyses suggest that during evolution the mutational pressure has been optimised to some extent to the selection requirements.

Algorithms↗

PubMed2004

Tracing sequence diversity change of RNA-cleaving deoxyribozymes under increasing selection pressure during in vitro selection.

In vitro selection has been used extensively over the past 10 years to create functionally diverse DNA enzymes. The majority of in vitro selection experiments to date have focused on the outcome rather than the process itself, a process that remains to be fully elucidated. In vitro selection techniques rely on the probability that some DNA molecules in a random-sequence library will fold into an appropriate tertiary structure and catalyze a desired reaction. Thus, sufficient sequence diversity in the DNA pool (and hence more catalytic DNA sequences) is a prerequisite for the successful isolation of efficient deoxyribozymes. The catalytic sequence diversity established by in vitro selection is governed largely by the choice of selection pressures, one of which is the length of the reaction time. The objective of this study was to evaluate the sequence diversity change of a pool of RNA-cleaving deoxyribozymes as a function of the reaction time. Seventeen rounds of in vitro selection were performed, and the reaction time was progressively decreased from 5 h to 5 s. A representative population from each time class was subsequently cloned and sequenced. A decline in sequence diversity was observed with decreasing reaction time, and the relationship appears to be logarithmic. In contrast, a control selection performed with a constant reaction time during each round led to a linear and comparatively very slow decrease in sequence diversity. This study provides the first methodical examination of the change in catalytic sequence diversity that occurs through the course of a deoxyribozyme selection experiment. Moreover, it represents a first step toward fully understanding the intricate pathway that lies between the beginning and end of an in vitro selection experiment.

Base Sequence↗

PubMed2006

Can biochemical properties serve as selective pressure for gene selection during inter-species and endosymbiotic lateral gene transfer?

During the evolution of endosymbiosis, only one orthologous gene, either from the invader or the invaded genome, is preserved. Genetic and environmental factors are usually invoked to explain this gene preference. How biochemical parameters can play a role in the selection of genes that code for enzymes that constitute a metabolic pathway is explored. Simple Michaelis-Menten-like enzymes are considered whose kinetic parameters are randomly generated to construct two parallel homologous pathways to account for the contributions of the invaded and the invader. Steady-state fluxes as targets of natural selection are focused. Enzymes are eliminated one by one so that the total flux through the pathway is least disturbed. Analysis of the results, done by different criteria, indicate that the maximal velocities, both forward and backward, are more influential in selection than the respective Michaelis constants. This inclination disappears as metabolite concentrations are increased. It is shown that kinetic selection criteria can result in a mosaicism of enzymes in the same pathway in terms of their genetic origin. Analysis of the results using the control coefficient paradigm disclosed an expected robust correlation between flux control coefficients of enzymes and their selective elimination. Similar analyses, performed for the case of single gene transfer or for gene replication with subsequent mutation, yielded essentially similar results. The results conform with the phenomenon of genetic mosaicism found in phylogenetic analyses of single or double endosymbioses and lateral gene transfer.

Animals↗

PubMed2000

A group of V3 sequences from human immunodeficiency virus type 1 subtype E non-syncytium-inducing, CCR5-using variants are resistant to positive selection pressure.

In a human immunodeficiency virus type 1 (HIV-1)-infected individual, immune-pressure-mediated positive selection operates to maintain the antigenic polymorphism on the gp120 third variable (V3) loop. Recently, we suggested on the basis of sequencing C2/V3 segments from an HIV-1 subtype E-infected family that a V3 sequence lineage group of the non-syncytium-inducing (NSI) variants (group 1) was relatively resistant to positive selection pressure (35). To better understand the relationship between the intensity of positive selection pressure and cell tropism of the virus, we determined the linkage between each V3 genotype and its function of directing coreceptor preference and MT2 cell tropism. The biological characterization of a panel of V3 recombinant viruses showed that all of the group 1 V3 sequences could confer an NSI/CCR5-using (NSI/R5) phenotype on HIV-1(LAI), whereas the group 2 V3 sequence, which was more positively charged than the group 1 sequence, dictated mainly a syncytium-inducing, CXCR4-using (SI/X4) phenotype. Phylogenetic analysis of C2/V3 sequences encoding group 1 or 2 V3 suggested that the variants carrying group 1 V3 are the ancestors of the intrafamilial infection and persisted in the family, while the variants carrying group 2 V3 evolved convergently from the group 1 V3 variants during disease progression in the individuals. Finally, a statistical test showed that the V3 sequence that could dictate an NSI/R5 phenotype had a synonymous substitution rate significantly higher than the nonsynonymous substitution rate. These data suggest that V3 sequences of the subtype E NSI/R5 variants are more resistant to positive selection pressure than those of the SI/X4 variants.

Adult↗

PubMed2005

The resistance ratchet: theoretical implications of cyclic selection pressure.

OBJECTIVES: To investigate the effects of cyclic antibiotic selection pressure on resistance in a simple mathematical model. METHODS: The model assumed that resistance in microbial ecologies changes slowly with changing selection pressure, at a rate proportional to the difference between the current resistance level and the resistance level that would be in equilibrium with current selection pressure. The maximum rate of increase in resistance during periods of increasing selection was assumed to be greater than the maximum rate of decrease during decreased selection. RESULTS: Under a simulated annual cyclic selection pressure variation of 40%, with maximum resistance rise and fall rates of 10 and 0.5%, respectively, resistance rose above the level expected from the mean selection pressure by small ratchet-like increments. Over 50 simulated years, resistance increased to 62%, rather than the 50% expected from the mean level of selection. Welsh community prescribing for a selection of antibiotics showed a seasonal cyclic variation of 13-45%. CONCLUSIONS: The intuitive assumption that cyclic selective pressure would produce resistance levels commensurate with the mean selection pressure was contradicted; rather resistance drifted towards a level commensurate with maximum selection pressure. If the ratchet effect exists in reality, it may produce unexpected excess resistance, particularly in the community for antibiotics used in respiratory infection, where cycling is pronounced, or in ITU antibiotic rotation. It should be most pronounced for resistance systems with strong asymmetry between rates of adaptation under rising and falling selection pressure. Non-linear dynamic systems in physics and ecology are notorious for producing counter-intuitive effects; resistance epidemiology may be similar.

Anti-Bacterial Agents↗

PubMed2006

Can RNA selection pressure distort the measurement of Ka/Ks?

Recently, an interesting question has emerged in the evolutionary interpretation of sequence substitution data as evidence of amino acid selection pressure. Specifically, the Ka/Ks metric was designed to measure selection pressure on amino acid substitutions, assuming that the synonymous substitution rate Ks reflects the neutral nucleotide substitution rate. However, there is increasing evidence for selection pressure at silent sites due to constraints of RNA splicing. Is Ka/Ks an appropriate metric for selection pressure on amino acid substitutions, in the presence of other selection pressures acting only at the RNA level (such as selection for exonic splicing enhancers)? Or can the resulting decreases in Ks from such selection pressures introduce bias into the Ka/Ks metric, so that it no longer gives an accurate measure of amino acid level selection pressure? In this review, we present both mathematical models and empirical evidence for these divergent points of view.

Amino Acid Substitution↗

PubMed2004

Application of maximum-likelihood models to selection pressure analysis of group I nucleopolyhedrovirus genes.

Knowledge of virus genes under positive selection pressure can help identify molecular determinants of species-specific virulence or host range without prior knowledge of the mechanisms governing host range and virulence. Towards this end, codon-based models of substitution were used in a maximum-likelihood approach to analyse selection pressures acting on 83 genes of group I nucleopolyhedroviruses (NPVs). Evidence for positive selection was found for nine genes: ac38, ac66, arif-1, lef-7, lef-10, lef-12, odv-e18, odv-e56 and vp80. The baculovirus DNA helicase gene (dnahel) was not found to be positively selected using models that allowed the intensity of selection pressure to vary among codon sites. Further analysis with a method that allows selection pressure intensity to vary among lineages suggests that positive selection may have occurred in dnahel during the divergence of Bombyx mori NPV and the NPVs of Autographa californica and Rachiplusia ou. NPV genes that have undergone positive selection may modulate the ability of different NPVs to replicate efficiently in cells (lef-7, lef-10, lef-12) or to establish primary infection of the midgut (odv-e18, odv-e56) of different host species.

Animals↗

PubMed2006

Antimicrobial drugs that target human--not microbial--genotypes or phenotypes: a paradigm change in human evolutionary response to pathogen selection pressure.

Conventional antimicrobial drugs that target microbial life processes impose a selection pressure on pathogens and attenuate pathogen imposed selection pressure on human hosts. The simultaneous increase and decrease that result in pathogen and human host evolvability/adaptability, respectively, distorts the natural Darwinian evolutionary process. Such drugs may create an aberrant Darwinian genotype in human hosts that is ill prepared to resist emerging virulent pathogenic strains in the event of a decrease in host ontogenic potential. In contrast, antimicrobial drugs that target host human genes exert a selective pressure both on the human genome (without population decimation) as well as on pathogenic microbes. Such drugs maintain the evolvability/adaptability of the host in tandem with that of the pathogens in the context of Darwinian evolution. Such drugs retain the capacity of the human host to evolve genotypes that may confer resistance to future pathogenic microbial strains, to assimilate prokaryotic endosymbionts and to increase the probability of survival in the event of a decrease in host ontogenic potential.

Anti-Infective Agents↗

PubMed2005

Evidence of functional selection pressure for alternative splicing events that accelerate evolution of protein subsequences.

Recently, it was proposed that alternative splicing may act as a mechanism for opening accelerated paths of evolution, by reducing negative selection pressure, but there has been little evidence so far that this mechanism could produce adaptive benefit. Here, we use metrics of very different types of selection pressures [e.g., against amino acid mutations (Ka/Ks), against mutations at synonymous sites (Ks), and for protein reading-frame preservation] to address this question by genomewide analyses of human, chimpanzee, mouse, and rat. These data show that alternative splicing relaxes Ka/Ks selection pressure up to 7-fold, but intriguingly this effect is accompanied by a strong increase in selection pressure against synonymous mutations, which propagates into the adjacent intron, and correlates strongly with the alternative splicing level observed for each exon. These effects are highly local to the alternatively spliced exon. Comparisons of these four genomes consistently show an increase in the density of amino acid mutations (Ka) in alternatively spliced exons and a decrease in the density of synonymous mutations (Ks). This selection pressure against synonymous mutations in alternatively spliced exons was accompanied in all four genomes by a striking increase in selection pressure for protein reading-frame preservation, and both increased markedly with increasing evolutionary age. Restricting our analysis to a subset of exons with strong evidence for biologically functional alternative splicing produced identical results. Thus alternative splicing apparently can create evolutionary "hotspots" within a protein sequence, and these events have evidently been selected for during mammalian evolution.

Alternative Splicing↗

PubMed2002

Codon-substitution models to detect adaptive evolution that account for heterogeneous selective pressures among site classes.

The nonsynonymous to synonymous substitution rate ratio (omega = d(N)/d(S)) provides a sensitive measure of selective pressure at the protein level, with omega values <1, =1, and >1 indicating purifying selection, neutral evolution, and diversifying selection, respectively. Maximum likelihood models of codon substitution developed recently account for variable selective pressures among amino acid sites by employing a statistical distribution for the omega ratio among sites. Those models, called random-sites models, are suitable when we do not know a priori which sites are under what kind of selective pressure. Sometimes prior information (such as the tertiary structure of the protein) might be available to partition sites in the protein into different classes, which are expected to be under different selective pressures. It is then sensible to use such information in the model. In this paper, we implement maximum likelihood models for prepartitioned data sets, which account for the heterogeneity among site partitions by using different omega parameters for the partitions. The models, referred to as fixed-sites models, are also useful for combined analysis of multiple genes from the same set of species. We apply the models to data sets of the major histocompatibility complex (MHC) class I alleles from human populations and of the abalone sperm lysin genes. Structural information is used to partition sites in MHC into two classes: those in the antigen recognition site (ARS) and those outside. Positive selection is detected in the ARS by the fixed-sites models. Similarly, sites in lysin are classified into the buried and solvent-exposed classes according to the tertiary structure, and positive selection was detected at the solvent-exposed sites. The random-sites models identified a number of sites under positive selection in each data set, confirming and elaborating the results of the fixed-sites models. The analysis demonstrates the utility of the fixed-sites models, as well as the power of previous random-sites models, which do not use the prior information to partition sites.

Alleles↗

PubMed2006

Identification of physicochemical selective pressure on protein encoding nucleotide sequences.

BACKGROUND: Statistical methods for identifying positively selected sites in protein coding regions are one of the most commonly used tools in evolutionary bioinformatics. However, they have been limited by not taking the physiochemical properties of amino acids into account. RESULTS: We develop a new codon-based likelihood model for detecting site-specific selection pressures acting on specific physicochemical properties. Nonsynonymous substitutions are divided into substitutions that differ with respect to the physicochemical properties of interest, and those that do not. The substitution rates of these two types of changes, relative to the synonymous substitution rate, are then described by two parameters, gamma and omega respectively. The new model allows us to perform likelihood ratio tests for positive selection acting on specific physicochemical properties of interest. The new method is first used to analyze simulated data and is shown to have good power and accuracy in detecting physicochemical selective pressure. We then re-analyze data from the class-I alleles of the human Major Histocompatibility Complex (MHC) and from the abalone sperm lysine. CONCLUSION: Our new method allows a more flexible framework to identify selection pressure on particular physicochemical properties.

Algorithms↗

PubMed1999

Higher selection pressure from antiretroviral drugs in vivo results in increased evolutionary distance in HIV-1 pol.

We investigated the effect of selection pressures on evolution of HIV-1 pol in 51 patients after switching to a new antiretroviral combination reverse transcriptase (RT) inhibitor therapy. Evolution of the protease (PR) and RT reading frames were analysed separately. Pairwise evolutionary distances (ED) were calculated between sequences from baseline and week 8 and between baseline and week 48 of protocol therapy. ED were calculated for all substitutions and for synonymous and nonsynonymous substitutions separately. At week 8 when HIV RNA reduction (selection pressure) was high, significantly more divergence in pol in both synonymous and nonsynonymous substitutions was found in patients with substantial RNA reduction (strong responders). Separate analyses of PR and RT revealed significantly greater ED in the RT (under selection pressure) of strong compared with nonresponders, whereas divergence between PR genes (not under selection pressure) did not differ in those two groups. Such differential evolution indicates that PR and RT were genetically unlinked and suggests recombination. The rapid increase of ED over the first 8 weeks was followed by only a minimal further rise by week 48, suggesting that selection of preexisting quasispecies accounted for the early changes. A disproportionally high number of synonymous substitutions accounted for the observed divergence and indicated that such genetic changes may not be completely silent.

Anti-HIV Agents↗

PubMed2000

Maximum-likelihood analysis of molecular adaptation in abalone sperm lysin reveals variable selective pressures among lineages and sites.

Maximum-likelihood models of codon substitution were used to analyze sperm lysin genes of 25 abalone (HALIOTIS:) species to identify lineages and amino acid sites under diversifying selection. The models used the nonsynonymous/synonymous rate ratio (omega = d(N)/d(S)) as an indicator of selective pressure and allowed the ratio to vary among lineages or sites. Likelihood ratio tests suggested significant variation in selective pressure among lineages. The variable selective pressure provided an explanation for the previous observation that the omega ratio is >1 in comparisons of closely related species and <1 in comparisons of distantly related species. Computer simulations demonstrated that saturation of nonsynonymous substitutions and constraint on lysin structure were unlikely to account for the observed pattern. Lineages linking closely related sympatric species appeared to be under diversifying selection, while lineages separating distantly related species from different geographic locations were associated with low evolutionary rates. The selective pressure indicated by the omega ratio was found to vary greatly among amino acid sites in lysin. Sites under potential diversifying selection were identified. Ancestral lysins were inferred to trace the route of evolution at individual sites and to provide lysin sequences for future laboratory studies.

Adaptation, Biological↗

PubMed2006

Transmission of Salmonella enterica serotype Typhimurium in poultry with and without antimicrobial selective pressure.

AIMS: To determine the effect of antimicrobial selective pressure on the transmission of antimicrobial resistant and sensitive strains of Salmonella in poultry. METHODS AND RESULTS: Eight pens housed 12 broiler chicks each. Two chicks in four of the pens were inoculated with a Salm. Typhimurium strain resistant to 12 antimicrobials (including tetracycline), and two chicks in each of the four other pens were inoculated with a strain sensitive to all antimicrobials tested. Two pens inoculated with each strain were treated with chlortetracycline and two were not. Chicks were killed on day 7 and caeca were cultured for Salmonella. Experiments were performed independently twice. Chicks exposed to pen mates inoculated with the resistant strain and treated with tetracycline were 90% positive for Salmonella; whereas 60% of chicks given no antimicrobials were positive. Chicks exposed to the sensitive strain were 95% positive with tetracycline treatment and 90% positive without treatment. CONCLUSIONS: A multidrug-resistant Salm. Typhimurium strain had significantly increased transmission when chicks were treated with tetracycline. Transmission of a sensitive strain was not inhibited by antimicrobial selective pressure at recommended therapeutic dose. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates that antimicrobial usage may influence the transmission of antimicrobial-resistant pathogens in poultry.

Animal Husbandry↗

PubMed1977

Spontaneous implantation of antibiotic-resistant Enterobacteriaceae in the digestive tract of chickens in the absence of selective pressure.

In the absence of selective pressure by antibiotics, resistant enterobacteria implanted rapidly in the intestinal tract of chickens, where these organisms subsequently persisted in high numbers. Food could be an important source of this contamination: resistant Escherichia coli present in small numbers in the diet became rapidly and persistently established in the gut. The human caretaker played a passive role in the spread of antibiotic-resistant bacteria between separate groups of chickens. Resistant enteric organisms colonized the gut of animals, with different population sizes. Some strains were able to reach high numbers (10(7) to 10(9)/g), and other strains established themselves at a lower level (10(3) to 10(5)/g), whereas a third type seemed to be only transient inhabitants, unable to persist.

Animals↗

PubMed1992

Equal G and C contents in histone genes indicate selection pressures on mRNA secondary structure.

Protein-specific versus taxon-specific patterns of nucleotide frequencies were studied in histone genes. The third positions of codons have a (well-known) taxon-specific G+C level and a histone type-specific G/C ratio. This ratio counterbalances the G/C ratio in the first and second positions so that the overall G and C levels in the coding region become approximately equal. The compensation of the G/C ratio indicates a selection pressure at the mRNA level rather than a selection pressure or mutation bias at the DNA level or a selection pressure on codon usage. The structure of histone mRNAs is compatible with the hypothesis that the G/C compensation is due to selection pressures on mRNA secondary structure. Nevertheless, no specific motifs seem to have been selected, and the free energy of the secondary structures is only slightly lower than that expected on the basis of nucleotide frequencies.

Animals↗

PubMed2005

In vitro evolutionary thermostabilization of congerin II: a limited reproduction of natural protein evolution by artificial selection pressure.

The thermostability of the conger eel galectin, congerin II, was improved by in vitro evolutionary protein engineering. Two rounds of random PCR mutagenesis and selection experiments increased the congerin II thermostability to a level comparative to its naturally thermostable isoform, congerin I. The crystal structures of the most thermostable double mutant, Y16S/T88I, and the related single mutants, Y16S and T88I, were determined at 2.0 angstroms, 1.8 angstroms, and 1.6 angstroms resolution, respectively. The exclusion of two interior water molecules by the Thr88Ile mutation, and the relief of adjacent conformational stress by the Tyr16Ser mutation were the major contributions to the thermostability. These features in the congerin II mutants are similar to those observed in congerin I. The natural evolution of congerin genes, with the K(A)/K(S) ratio of 2.6, was accelerated under natural selection pressures. The thermostabilizing selection pressure artificially applied to congerin II mimicked the implied natural pressure on congerin I. The results showed that the artificial pressure made congerin II partially reproduce the natural evolution of congerin I.

Amino Acid Sequence↗

PubMed2000

[Selective pressure in host-parasite systems].

Selective pressures in host-parasite systems are the result of a continuous conflict between the divergent interests of each partner, on the long run. Whereas the fitness (lifetime reproductive success) of parasites is usually increased by a higher frequency of encounters with susceptible hosts and a better survival rate after infection, the fitness of hosts is increased by opposite processes, avoidance of encounters with infective stages and destruction of the parasites. These selective processes, often referred to as coevolution or arms races are in agreement with the Red Queen hypothesis of Van Valen, which assumes indefinite adaptive changes in both partners, in order to set up counter-measures against the weapons of "the other". Arms races in host-parasite systems thus suggest a gradualistic evolution, but this does not contradict the present day ideas on the tempo changes in the course of evolution (punctuated equilibria). Numerous factors, either genetic (evolutionary lag...), environmental (nutritional status...) or cultural (prevention, vaccination, therapy...) influence the severity of infections at an individual scale. The "terrain", which is a component of the individual phenotype, is thus at the cross-roads of genes, environment and culture. Humans must count more on their intelligence than on natural selection to prevent and cure infectious and parasitic diseases.

Adaptation, Physiological↗