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PubMed2003

BAGE genes generated by juxtacentromeric reshuffling in the Hominidae lineage are under selective pressure.

In this paper, we show that the BAGE (B melanoma antigen) gene family was generated by chromosome rearrangements that occurred during the evolution of hominoids. An 84-kb DNA fragment derived from the phylogenetic 7q36 region was duplicated in the juxtacentromeric region of either chromosome 13 or chromosome 21. The duplicated region contained a fragment of the MLL3 gene, which, after juxtacentromeric reshuffling, generated the ancestral BAGE gene. Then, this ancestral gene gave rise to several independent genes through successive rounds of inter- and intrachromosome duplications. Comparison of synonymous and nonsynonymous mutations in putative coding regions shows that BAGE genes, but not the BAGE gene fragments, are under selective pressure. Our data strongly suggest that BAGE proteins have a function and that juxtacentromeric regions, whose plasticity is now largely proved, are not a simple junkyard of gene fragments, but may be the birth site of novel genes.

Animals↗
PubMed1999

Cytogenetic analysis of chimeric antibody-producing CHO cells in the course of dihydrofolate reductase-mediated gene amplification and their stability in the absence of selective pressure.

Previously, the highest producing (HP) recombinant CHO subclones isolated at various methotrexate (MTX) levels showed different antibody production stability during long-term culture, although they were clonally derived from CS13 transformant. In this study, genetic basis for their difference in antibody production stability was investigated using southern blot hybridization and fluorescence in situ hybridization (FISH) techniques. Southern analysis of HP subclones revealed that light-chain (LC) and heavy-chain (HC) cDNAs were located closely within 23 kb on an amplification unit, and the configuration of LC and HC cDNAs within this amplification unit was not disrupted during long-term culture in the absence of MTX. However, when LC and HC genes were localized on the metaphase chromosomes of HP subclones using FISH, the amplified sequences were present as an extended array on diverse marker chromosomes. HP subclones selected at higher MTX level had more kinds of marker chromosomes. CS13*-002 isolated at 0.02 microM MTX had only one marker chromosome (m002), whereas CS13*-1.0 isolated at 1 microM MTX had five different ones (m10A, m10B, m10C, m10D, and m10E). Each marker chromosome showed different fate during long-term culture of HP subclones in the absence of MTX, resulting in different degrees of stability among the HP subclones. The m10A and m10B remained unchanged, whereas the others disappeared or evolved to variants with shortened amplified arrays. The cells containing stable marker chromosomes constituted dominant subpopulations in CS13*-1.0, and thereby CS13*-1.0 became most stable in regard to antibody production during long-term culture. Furthermore, our dual-color FISH showed that the telomeric ends of amplified arrays on the stable marker chromosomes were always surrounded by (TTAGGG)(n) sequences, indicating that (TTAGGG)(n) sequences are closely related to the stability and evolution of amplified sequences. Taken together, our data show that the assessment of genotypic stability of amplified CHO cells is a prerequisite for understanding their production stability during long-term culture in the absence of selection pressure.

Animals↗
PubMed2002

Selection pressure towards monoxeny in Camallanus cotti (Nematoda, Camallanidac) facing an intermediate host bottleneck situation.

This paper describes the ability of the Asian fish nematode Camallanus cotti to carry out both heteroxeny, i.e. an indirect life-cycle using copepods as intermediate host, and monoxeny, i.e. direct infection and development in the definitive fish host. C. cotti occurs naturally in various freshwater teleosts in Asia. During the past decades it has been disseminated into closed or semi-closed aquaculture systems and aquaria around the world, mainly due to the ornamental fish trade. Under such conditions the species may frequently face a bottleneck situation with regard to the availability of copepods. It is known that C. cotti may reproduce and persist in copepod-free aquaria for several months. In order to investigate whether C. cotti has selected towards monoxeny in water systems lacking copepods, in contrast to the opposite selection pressure when copepods are present, 2 separate infection trials were run. It was shown that the parasite can infect the fish host both indirectly via copepods, and directly. However, C. cotti has significantly higher fitness, expressed as survival to maturity, when transmitted indirectly compared to the direct transmission mode. We suggest that the ability of aquarium populations of C. cotti to carry out a direct life-cycle is favoured by selection in order to avoid extinction whenever copepods are absent. It still remains unknown, however, whether the parasite shows the same characteristics in the wild.

Animals↗
PubMedDate not supplied

Treatment of Plasmodium falciparum malaria with pyrimethamine-sulfadoxine: selective pressure for resistance is a function of long elimination half-life.

In an area of continuing transmission of Plasmodium falciparum on the Kenya coast, children treated with pyrimethamine-sulfadoxine experienced rapid parasite clearance, although a high proportion became reinfected within a short time. The frequency of pyrimethamine resistance in vitro in new infections was higher during the elimination phase of drug from a previous treatment. In infections which occurred at times when predicted residual drug concentrations were no longer inhibitory, incidence of pyrimethamine resistance was no different from the natural or background frequency. These results are discussed in terms of the selective pressure for resistance which is exerted by drugs with long elimination half-lives and a consideration of possible ways by which the problem might be addressed.

Animals↗
PubMed2004

Negative selection pressure against premature protein truncation is reduced by alternative splicing and diploidy.

The importance of alternative splicing in many genomes has raised interesting questions about its role in evolution. We analyzed 13 384 full-length transcript isoforms from human and 2227 isoforms from mouse to identify sequences containing premature termination codons (PTCs) that are likely targets of mRNA nonsense-mediated decay. We found that alternatively spliced isoforms have a much higher frequency of PTCs (11.1%) compared with the major transcript form of each gene (3.7%). On the X chromosome, which is generally expressed as a single copy, the overall PTC rate was much lower (3.5%, versus 8.9% on diploid autosomes), and the effect of alternative splicing was enhanced. Thus, diploidy and alternative splicing each increased tolerance for PTC by about threefold, as approximately additive effects. These data suggest that nonsense mediated decay might itself reduce negative selection pressure during evolution, via rapid degradation of aberrant transcripts that might yield dominant negative phenotypes.

Alternative Splicing↗
PubMed2005

Molecular footprint of drug-selective pressure in a human immunodeficiency virus transmission chain.

Known human immunodeficiency virus (HIV) transmission histories are invaluable models for investigating the evolutionary and transmission dynamics of the virus and to assess the accuracy of phylogenetic reconstructions. Here we have characterized an HIV-1 transmission chain consisting of nine infected patients, almost all of whom were treated with antiviral drugs at later stages of infection. Partial pol and env gp41 regions of the HIV genome were directly sequenced from plasma viral RNA for at least one sample from each patient. Phylogenetic analyses in pol using likelihood methods inferred an evolutionary history not fully compatible with the known transmission history. This could be attributed to parallel evolution of drug resistance mutations resulting in the incorrect clustering of multidrug-resistant virus. On the other hand, a fully compatible phylogenetic tree was reconstructed from the env sequences. We were able to identify and quantify the molecular footprint of drug-selective pressure in pol using maximum likelihood inference under different codon substitution models. An increased fixation rate of mutations in the HIV population of the multidrug-resistant patient was demonstrated using molecular clock modeling. We show that molecular evolutionary analyses, guided by a known transmission history, can reveal the presence of confounding factors like natural selection and caution should be taken when accurate descriptions of HIV evolution are required.

Anti-HIV Agents↗
PubMed1999

Recombination between genomic RNAs of two cucumoviruses under conditions of minimal selection pressure.

Recombination is considered to play a key role in RNA virus evolution; however, little is known about its occurrence under natural conditions. We inoculated tobacco plants with wild-type strains of two closely related cucumovirus species: cucumber mosaic virus (CMV) and tomato aspermy virus (TAV). RNA from the inoculated leaves of doubly-infected plants was tested for the presence of recombination events in an 0.8-kb central portion of the viral RNA3. Using a sensitive and specific RT-PCR procedure, we amplified recombinant segments of RNA3 in 3 of 82 tobacco plants infected with both viruses. In each plant in which recombinant segments were amplified, several different crossover sites were observed, all of which were located within a short stretch of high sequence similarity. Two plants had both CMV-TAV and TAV-CMV recombinants. In all cases, precise homologous recombination had occurred. To the best of our knowledge, this is the first report of interspecific recombination between wild-type plant RNA viruses under conditions of minimal selection pressure in favor of the recombinants.

Base Sequence↗
PubMed1990

DNA recombination and natural selection pressure sustain genetic sequence diversity of the feline MHC class I genes.

Sequence comparisons of seven distinct MHC class I cDNA clones revealed that feline class I molecules have a remarkable similarity to human HLA genes in their organization of functional domains as well as in the nonrandom partitioning of genetic variability according to the functional constraints ascribed to different regions of the MHC molecule. The distribution of the pattern of sequence polymorphism in the cat as compared with genetic diversity of human and mouse class I genes provides evidence for four coordinate factors that contribute to the origin and sustenance of abundant allele diversity that characterizes the MHC in the species. These include: (a) a gradual accumulation of spontaneous mutational substitution over evolutionary time; (b) selection against mutational divergence in regions of the class I molecule involved in T cell receptor interaction and also in certain regions that interact with common features of antigens; (c) positive selection pressure in favor of persistence of polymorphism and heterozygosity at 57 nucleotide residues that comprise the antigen recognition site; and (d) periodic intragenic (interallelic) and intergenic recombination within the class I genes. We describe a highly conserved 23-bp nucleotide sequence within the coding region of the first alpha-helix that separates two relatively polymorphic segments located in the alpha 1 domain that may act as a template or "hot spot" for homologous recombination between class I alleles.

Amino Acid Sequence↗
PubMed2006

Immune selective pressure and HLA class I antigen defects in malignant lesions.

The revived cancer immune surveillance theory has emphasized the active role the immune system plays in eliminating tumor cells and in facilitating the emergence of their immunoresistant variants. MHC class I molecule abnormalities represent, at least in part, the molecular phenotype of these escape variants, given the crucial role of MHC class I molecules in eliciting tumor antigen-specific T cell responses, the high frequency of HLA class I antigen abnormalities in malignant lesions and their association with a poor clinical course of the disease. Here, we present evidence for this possibility and review the potential mechanisms by which T cell selective pressure participates in the generation of tumor cells with MHC class I molecule defects. Furthermore, we discuss the strategies to counteract tumor cell immune evasion.

Animals↗
PubMed2005

The plasmodial apicoplast was retained under evolutionary selective pressure to assuage blood stage oxidative stress.

Malaria, the clinical disease resulting from infection with Plasmodium, has haunted mankind with illness and death for thousands of years. As Plasmodia's ancient ancestor evolved from a mixotroph to an intracellular parasite, subsiding on amino acids obtained from hemoglobin, it encountered increased oxidative stress. To compensate for this oxidative stress, Plasmodia reduced its own production of reactive oxygen species by becoming largely fermentative and adapted novel methods to assuage oxidative injury. One such method appears to have been accomplished through the acquisition, retention and exploitation of an ancient red algal endosymbiote, now denoted the apicoplast. The apicoplast, located in close proximity to mitochondria, appears to synthesize the potent antioxidant lipoic acid. Lipoic acid may be utilized by Plasmodium as an antioxidant, a shuttle for reducing potentials and as a mitochondrial cofactor. Inhibition or alteration of the apicoplast leads to a curious phenomena known as "delayed death", whereby parasites die not in the present generation but in the ensuing one. Apicoplast inhibition may produce lipoic acid "starvation", increasing oxidative stress/mitochondrial injury during the subsequent asexual reproductive cycle. Collectively, data available to date indicate that the apicoplast was retained as an obligate endosymbiote, under evolutionary selective pressure, to assuage oxidative stress and plays a critical role in maintaining parasite viability during the Plasmodial shizont blood stage.

Animals↗
PubMed2000

Evolution of sequence recognition by restriction-modification enzymes: selective pressure for specificity decrease.

Several type II restriction-modification (RM) gene complexes kill host bacterial cells that have lost them, through attack on the chromosomal recognition sites of these cells. Two RM gene complexes recognizing the same sequence cannot simultaneously enjoy such stabilization through postsegregational host killing, because one will defend chromosomal sites from attack by the other. In the present work, we analyzed intrahost competition between two RM gene complexes when the recognition sequence of one was included in that of the other. When the EcoRII gene complex, recognizing 5'-CCWGG (W = A, T), is lost from the host, the SsoII gene complex, which recognizes 5'-CCNGG (N = A, T, G, C), will prevent host death by protecting CCWGG sites on the chromosome. However, when the SsoII (CCNGG) gene complex is lost, the EcoRII (CCWGG) gene complex will be unable to prevent host death through attack by SsoII on 5'-CCSGG (S = C, G) sites. These predictions were verified in our experiments, in which we analyzed plasmid maintenance, cell growth, cell shape, and chromosomal DNA. Our results demonstrate the presence of selective pressure for decrease in the specificity of recognition sequence of RM systems in the absence of invading DNA.

Cell Division↗
PubMed2003

Human cytomegalovirus glycoprotein N (gpUL73-gN) genomic variants: identification of a novel subgroup, geographical distribution and evidence of positive selective pressure.

Human cytomegalvirus (HCMV) ORF UL73 is a polymorphic locus, encoding the viral glycoprotein gpUL73-gN, a component of the gC-II envelope complex. The previously identified gN genomic variants, denoted gN-1, gN-2, gN-3 and gN-4, were further investigated in this work by analysing a large panel of HCMV clinical isolates collected from all over the world (223 samples). Sequencing and phylogenetic analysis confirmed the existence of the four gN genotypes, but also allowed the identification of a novel subgroup belonging to the gN-3 genotype, which was designated gN-3b. The number of non-synonymous (d(N)) and synonymous (d(S)) nucleotide substitutions and their ratio (d(N)/d(S)) were estimated among the gN genotypes to evaluate the possibility of positive selection. Results showed that the four variants evolved by neutral (random) selection, but that the gN-3 and gN-4 genotypes are maintained by positive selective pressure. The 223 HCMV clinical isolates were subdivided according to their geographical origin, and four main regions of gN prevalence were identified: Europe, China, Australia and Northern America. The gN variants were found to be widespread and represented within the regions analysed without any significant difference, and no new genotype was detected. Finally, for clinical and epidemiological purposes, a rapid and low-cost method for genetic grouping of the HCMV clinical isolates was developed based on the RFLP revealed by SacI, ScaI and SalI digestion of the PCR-amplified UL73 sequence. This technique enabled us to distinguish all four gN genomic variants and also their subtypes.

Amino Acid Sequence↗
PubMed1992

Effects of selective pressure block of Y-type optic nerve fibers on the receptive-field properties of neurons in the striate cortex of the cat.

In an aseptic operation under surgical anesthesia, one optic nerve of a cat was exposed and subjected to pressure by means of a special cuff. The conduction of impulses through the pressurized region was monitored by means of electrodes which remained in the animal after the operation. The pressure was adjusted to selectively eliminate conduction in the largest fibers (Y-type) but not in the medium-size fibers (X-type). The conduction block is probably due to a demyelination and remains complete for about 3 weeks. Within 2 weeks after the pressure-block operation, recordings were made from single neurons in the striate cortex (area 17, area V1) of the cat anesthetized with N2O/O2 mixture supplemented by continuous intravenous infusion of barbiturate. Neurons were activated visually via the normal eye and via the eye with the pressure-blocked optic nerve ("Y-blocked eye"). Several properties of the receptive fields of single neurons in area 17 such as S (simple) or C (complex) type of receptive-field organization, size of discharge fields, orientation tuning, direction-selectivity indices, and end-zone inhibition appear to be unaffected by removal of the Y-type input. On the other hand, the peak discharge rates to stimuli presented via the Y-blocked eye were significantly lower than those to stimuli presented via the normal eye. As a result, the eye-dominance histogram was shifted markedly towards the normal eye implying that there is a significant excitatory Y-type input to area 17. In a substantial proportion of area 17 neurons, this input converges onto the cells which receive also non-Y-type inputs. In one respect, velocity sensitivity, removal of the Y input had a weak but significant effect. In particular, C (but not S) cells when activated via the normal eye responded optimally at slightly higher stimulus velocities than when activated via the Y-blocked eye. These results suggest that the Y input makes a distinct contribution to velocity sensitivity in area 17 but only in C-type neurons. Overall, our results lead us to the conclusion that the Y-type input to the striate cortex of the cat makes a significant contribution to the strength of the excitatory response of many neurons in this area. However, the contributions of Y-type input to the mechanism(s) underlying many of the receptive-field properties of neurons in this area are not distinguishable from those of the non-Y-type visual inputs.

Animals↗
PubMed1999

Interferon-alpha therapy exerts selective pressure on hepatitis C virus quasispecies equilibrium.

Two patients with chronic hepatitis C virus (HCV) genotype 2b infection were studied. They responded biochemically to interferon (IFN) but had early virological and later biochemical relapse. The HCV quasispecies equilibrium in these patients was studied by a combination of cloning, sequencing and construction of phylogenetic trees. Another patient with chronic HCV genotype 2b infection was followed every 6 months for 30 months (including one episode of biochemical exacerbation) to serve as the control. Quasispecies equilibrium drifted during IFN therapy but moved back in the direction of the original equilibrium during biochemical relapse. In the control patient, there was no significant drifting throughout the follow-up period. These data suggest that IFN therapy exerts selective pressure on HCV quasispecies equilibrium.

Adult↗
PubMed2006

Interplay of selective pressure and stochastic events directs evolution of the MEL172 satellite DNA library in root-knot nematodes.

According to the library model, related species can have in common satellite DNA (satDNA) families amplified in differing abundances, but reasons for persistence of particular sequences in the library during long periods of time are poorly understood. In this paper, we characterize 3 related satDNAs coexisting in the form of a library in mitotic parthenogenetic root-knot nematodes of the genus Meloidogyne. Due to sequence similarity and conserved monomer length of 172 bp, this group of satDNAs is named MEL172. Analysis of sequence variability patterns among monomers of the 3 MEL172 satellites revealed 2 low-variable (LV) domains highly reluctant to sequence changes, 2 moderately variable (MV) domains characterized by limited number of mutations, and 1 highly variable (HV) domain. The latter domain is prone to rapid spread and homogenization of changes. Comparison of the 3 MEL172 consensus sequences shows that the LV domains have 6% changed nucleotide positions, the MV domains have 48%, whereas 78% divergence is concentrated in the HV domain. Conserved distribution of intersatellite variability might indicate a complex pattern of interactions in heterochromatin, which limits the range and phasing of allowed changes, implying a possible selection imposed on monomer sequences. The lack of fixed species-diagnostic mutations in each of the examined MEL172 satellites suggests that they existed in unaltered form in a common ancestor of extant species. Consequently, the evolution of these satellites seems to be driven by interplay of selective constraints and stochastic events. We propose that new satellites were derived from an ancestral progenitor sequence by nonrandom accumulation of mutations due to selective pressure on particular sequence segments. In the library of particular taxa, established satellites might be subject to differential amplification at chance due to stochastic mechanisms of concerted evolution.

Animals↗
PubMed1987

Persistence of an antibiotic resistance plasmid in intestinal Escherichia coli of chickens in the absence of selective pressure.

We studied eight strains of Escherichia coli resistant to high levels of trimethoprim that were isolated over a 6-week period in a commercial breeding flock of broilers. The strains originated from fecal samples and from a carcass immediately after slaughter. Seven of eight strains belonged to the same infrequent biotype. They were also resistant to ampicillin and streptomycin, and some were resistant to tetracycline and potassium tellurite. All the strains transferred trimethoprim and ampicillin resistance to E. coli. Analysis of the donors and of the transconjugants by agarose gel electrophoresis after digestion by restriction endonucleases and by nucleic acid hybridization indicated that resistance to trimethoprim (dfrI) and to ampicillin (bla TEM-1) was mediated by a 65-kilobase plasmid, pIP1531. Persistence of resistance to trimethoprim and ampicillin in this flock was therefore due to two cumulative factors, both occurring in the absence of selective pressure, namely the dissemination of a particular plasmid between strains and the ability of an atypical E. coli strain to stably colonize many animals.

Ampicillin↗
PubMed2006

Evolution of gp85 gene of subgroup J avian leukosis virus under the selective pressure of antibodies.

Subgroup J Avian leucosis virus (ALV-J) strain NX0101 was inoculated into chicken embryo fibroblasts (CEF) monolayers in 6-well plates. The six wells of CEF inoculated with NX0101 were divided into groups A (without anti-ALV-J serum in the medium) and B (with anti-ALV-J serum in the medium), then viruses from each well of both groups were separately passed in CEF every 6 d and formed their independent passage lineages. For each lineage of both groups, gp85 genes of the viruses in the 10th, 20th and 30th passages were amplified, cloned and sequenced. The sequence data indicated that the homologies of gp85 at aa level between the primary virus and the passed viruses of different passages of 3 lineages in group A were 97.7%-99.7%; and the homologies of gp85 between the primary virus and the passed viruses of different passages of 3 lineages in group B were 93.8%-96.1%. Analysis of the ratios of nonsynonium (NS) vs synonium (S) mutations of nucleic acids demonstrated that NS/S in 3 highly variable (hr-) regions at aa#110-120, aa#141-151 and aa#189-194 of gp85 in 3 lineages of group A were 2 (8/4), 1(3/3) and 1.3 (4/3), however, NS/S in the same 3 hr-regions of group B were 4.1 (13/3), 4.7 (14/3) and 3.3 (11/3). This study is the first demonstration of influence of immune selective pressure on evolution of ALV-J gp85 by specific antibodies under the controlled in vitro experiments.

Animals↗
PubMed1999

Strong selective pressure for evolution of an Epstein-Barr virus LMP2B homologue in the rhesus lymphocryptovirus.

Latent membrane protein 2B (LMP2B) is expressed during latent Epstein-Barr virus (EBV) infection, but little is known about its role. The goal of this study was to determine whether an LMP2B homologue is conserved in the rhesus monkey lymphocryptovirus (LCV). Both rhesus LCV LMP2A and LMP2B genes were cloned and sequenced. The rhesus LCV LMP2B gene is positionally conserved, and the EBNA-2 responsiveness and the bidirectional nature of the LMP1-LMP2B promoter have also been functionally conserved. However, this region of the genome encoding the LMP1, LMP1-LMP2B promoter, and LMP2B first exon demonstrates the most dramatic nucleotide sequence divergence between human and nonhuman LCV observed to date. Evolution of the rhesus LCV LMP2B promoter and transcript despite the dynamic nature of this genomic region reflects strong selective pressure for a yet-to-be-identified LMP2B function.

Amino Acid Sequence↗