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Results for “compensatory evolution”

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At least 253 records · Page 14Linked to original sources
PubMed1988

Evidence of natural selection to maintain a functional domain outside of the 'core' in a large subclass of group I introns.

Comparison of three closely-related, homologous Group I introns reveals conservation of RNA secondary structure and some primary sequence outside of the characteristic Group I core structure. Further examination of forty Group I introns showed that all can be placed into one of two categories based on the length of the "loop L5" region (subtended by the base-paired sequences P and Q): short (21 to 38 bases) or long (59 to 295 bases). Despite the large variation in size and sequence, all nineteen of the long L5 introns share a common structure whose features include an adenine-rich bulge at a fixed distance from the P-Q pairing. This bulge is flanked by base-paired regions of greater than or equal to 6 base pairs on the core-proximal side and greater than or equal to 3 base pairs on the distal side. In the core-proximal helix there are a large number and high proportion of deviations from the consensus sequence that maintain base-pairing. These naturally-occurring compensatory base substitutions provide compelling phylogenetic support for the existence of this pairing and indicate that the conserved structure has a function in vivo.

Aspergillus↗
PubMed2002

Roles of diversifying selection and coordinated evolution in the evolution of amphibian antimicrobial peptides.

Antimicrobial peptides are expressed in the skin of amphibians and are used to prevent infection by microorganisms. Frog species store distinct collections of antimicrobial peptides that show variation in size, charge, conformation, and bactericidal activity, and so the evolution of antimicrobial peptide gene families may reflect the adaptive diversification of these loci. We examined the molecular evolution of antimicrobial peptide transcripts from hylid and ranid frog species. Our results show that after the gene family arose in the common ancestor of the Hylidae and Ranidae, before the divergence of these families in the Mesozoic, it subsequently diversified within these groups with numerous duplication events and divergence of loci. Moreover, we provide evidence that suggests that members of the antimicrobial peptide gene family have been subject to diversifying selection within both propiece and mature domains of hylids and solely within the mature domain of ranids. Finally, our results suggest that coordinated and compensatory amino acid replacements have occurred within the acidic propiece and cationic mature domain of hylid antimicrobial peptide precursors, as has been observed for mammalian defensin genes, but not among those of ranid precursors.

Amino Acid Sequence↗
PubMed1975

Growth hormone treatment in hypopituitary dwarfs: longitudinal psychological effects.

This is one of a series of studies on the psychological effects of medically induced growth in a group of hypopituitary dwarfs treated with Human Growth Hormone (HGH). Before treatment these dwarfs were found to be psychologically immature and hypoactive, without any manifestation of aggressive drives, and had an underlying low self-esteem when compared with the normal population. When compared with a matched group with constitutional growth delay the hypopituitary patients were found to use denial, whereas the control group used well-organized compensatory mechanisms (9). Immaturity was found in both groups. When the hypopituitary dwarfs reached adolescence they lacked the core attributes of masculinity or femininity and manifested some ambiguity or even inversion in their choice of gender role (10). This report deals with their psychological evolution in relation to physical growth.

Adolescent↗
PubMedDate not supplied

Rapid restructuring of bicoid-dependent hunchback promoters within and between Dipteran species: implications for molecular coevolution.

Interacting genetic elements need to coevolve if their joint function is to be maintained; for example, the correct binding of transcriptional regulators to defined binding sites in gene promoters needs to be maintained during evolution to ensure proper function. As part of a wider investigation into the molecular coevolution of the Dipteran homeodomain-bearing regulator bicoid (bcd) and Bcd-dependent promoters, we present data on the functional, structural, and sequence differences between the promoters of the segmentation gene hunchback (hb), in several species of Cyclorrhaphan (higher) Diptera. The result of phenocopying hb mutations using RNA interference (RNAi) in Musca domestica shows broadly similar functions to the hb gene in Drosophila melanogaster. However, the Bcd-binding sites in the hb promoters of Drosophila, Musca, and the two blowfly species Lucilia sericata and Calliphora vicina differ in copy number, sequence, orientation, and spacing. Furthermore, all promoters are subject to rapid turnover by slippage-like processes leading to high densities of short repetitive motifs. A study of polymorphism among six strains of M. domestica reveals that turnover by slippage also occurs in the promoter, untranslated leader, and exonic coding sequences of hb, but to different extents. We discuss these results in terms of the known interspecific differences in bcdand the potential coevolution of selected compensatory mutations in trans and cis in response to continuous promoter restructuring.

Animals↗
PubMed2002

The 'carnivore connection'--evolutionary aspects of insulin resistance.

Insulin resistance is common and is determined by physiological (aging, physical fitness), pathological (obesity) and genetic factors. The metabolic compensatory response to insulin resistance is hyperinsulinaemia, the primary purpose of which is to maintain normal glucose tolerance. The 'carnivore connection' postulates a critical role for the quantity of dietary protein and carbohydrate and the change in the glycaemic index of dietary carbohydrate in the evolution of insulin resistance and hyperinsulinaemia. Insulin resistance offered survival and reproductive advantages during the Ice Ages which dominated human evolution, during which a high-protein low-carbohydrate diet was consumed. Following the end of the last Ice Age and the advent of agriculture, dietary carbohydrate increased. Although this resulted in a sharp increase in the quantity of carbohydrate consumed, these traditional carbohydrate foods had a low glycaemic index and produced only modest increases in plasma insulin. The industrial revolution changed the quality of dietary carbohydrate. The milling of cereals made starch more digestible and postprandial glycaemic and insulin responses increased 2-3 fold compared with coarsely ground flour or whole grains. This combination of insulin resistance and hyperinsulinaemia is a common feature of many modern day diseases. Over the last 50 y the explosion of convenience and takeaway 'fast foods' has exposed most populations to caloric intakes far in excess of daily energy requirements and the resulting obesity has been a major factor in increasing the prevalence of insulin resistance.

Biological Evolution↗
PubMed1998

The Western Australian HIV Cohort Study, Perth, Australia.

The efficacy of primary prophylactic treatment for opportunistic infections can be estimated in an observational cohort study by adjusting for clinical and laboratory markers of the immunodeficiency (e.g., oral candidiasis, CD4%, lymphocyte cell counts) as time-dependent co-variates (providing that the treatment does not directly alter the markers). However, the CD4 cell count provides an incomplete measure of the protective immune response, and the efficacy of treatment may be underestimated if there is inadequate adjustment for the severity of immunodeficiency. Unlike prophylactic therapies, the efficacy of which remains relatively constant over time, antiretroviral therapy may produce only transient or time-limited benefits. This problem can be minimized by allowing the effect of antiretroviral therapy to vary over time in Cox proportional hazards models (i.e., to allow the antiretroviral therapy coefficient to change over time). Another difficulty is that CD4 cell counts may underestimate the degree of immunodeficiency after prolonged zidovudine (AZT) monotherapy. If post-antiretroviral therapy CD4 cell counts are used to adjust for the stage of immunodeficiency, it may therefore be helpful to adjust for the duration of antiretroviral therapy with the CD4 cell count at the time of starting antiretroviral therapy. It is interesting to consider statistical models of progressive HIV-induced immunodeficiency in the context of the evolution of host immunity. HIV infection results in the loss of the relatively recently evolved adaptive CD4 T cell-mediated immunity to intracellular parasites. The infected host may compensate for this by making greater use of phylogenetically ancient, more innate protective responses. Because these compensatory responses are polymorphic, this results in the appearance of differences between individuals in the immune response to HIV as the disease progresses. Data from the Western Australia HIV Cohort Study support a two-stage model of immunopathology. The first stage of this model involves a loss of mucosal immunity and occurs at a variable CD4 cell count (of between 400 cells/mm3 and zero), and is marked by a loss of cutaneous delayed-type hypersensitivity responses and oral candidiasis, seborrheic dermatitis, and Pneumocystis carinii pneumonia. The second stage of the model involves a loss of systemic immunity and requires profound CD4 T-cell lymphopenia (CD4 cell count <50 cells/mm3), and is marked by infections such as cytomegalovirus and disseminated Mycobacterium avium infection. The influence of HLA type on the risk for such opportunistic infections becomes apparent during this late phase.

AIDS-Related Opportunistic Infections↗
PubMed2006

Fitness of antimicrobial-resistant Campylobacter and Salmonella.

Campylobacter and Salmonella are the most commonly reported bacterial causes of human foodborne infections, and increasing proportions of these pathogens become resistant to medically important antimicrobial agents, imposing a burden on public health. Acquisition of resistance to antibiotics affects the adaptation and evolution of Salmonella and Campylobacter in various environments. Many resistance-conferring mutations entail a biological fitness cost, while others (e.g. fluoroquinolone resistance in Campylobacter) have no cost or even enhanced fitness. In Salmonella, the fitness disadvantage due to antimicrobial resistance can be restored by acquired compensatory mutations, which occur both in vitro and in vivo. The compensated or even enhanced fitness associated with antibiotic resistance may facilitate the spread and persistence of antimicrobial-resistant Salmonella and Campylobacter in the absence of selection pressure, creating a significant barrier for controlling antibiotic-resistant foodborne pathogens.

Animals↗
PubMed1996

A phylogeny for the African treefrog family Hyperoliidae based on mitochondrial rDNA.

Mitochondrial 12S rRNA sequences were used to construct a phylogeny for the African treefrog family, Hyperoliidae. The sequences were aligned using the well-established mt 12S rRNA secondary structure as a map to designate stem and loop positions. Conservation of secondary structure permits a more accurate basis for assessing homologies than does primary sequence alone. The molecular trees showed many similarities to the morphological trees constructed previously. Species within a genus always grouped together. The genera Hyperolius, Heterixalus, Afrixalus, and Kassina were resolved, but not with statistical significance. Leptopelis was the basal group. The analysis shows clearly that Phylyctimantis groups with Kassina as it did in Drewes' morphological tree and that Tachycnemis groups closely with Heterisxalus, a relationship not suggested by the morphological data. Character weighting (including compensatory base changes), mitochondrial trees vs gene trees, and the biogeography of the group are discussed.

Africa↗
PubMed1996

Epistasis and pleiotropy as natural properties of transcriptional regulation.

A statistical thermodynamic model of transcriptional regulation is employed to investigate the likely effects of genetic variation on the stabilization of gene expression. The model is tailored to empirical data on the control of transcription of the hunchback gene by the morphogen Bicoid during Drosophila embryogenesis. Variable parameters include the number of binding sites for activator protein and the DNA-protein and protein-protein cooperative binding energies. Recursions are performed to derive transcriptional response curves over a range of concentrations of activator. Sigmoidal responses are indicative of threshold-dependent activation of gene expression, and the effects of variation of the parameters on the width and location of the threshold are considered. It is shown that there is a minimum threshold width (maximum switch sensitivity) that is a function of the number of binding sites and the level of response desired, but independent of the binding energies. This places a constraint on the evolution of sensitive genetic switches that generate discrete cell types. Inevitable trade-offs between threshold widths and locations for multiple target genes of most transcriptional activators are found to occur. These naturally lead to epistatic and pleiotropic effects, and may favor the generation of networks of compensatory mutations that together produce homeostatic developmental pathways.

Animals↗
PubMed1982

[Compensatory growth in children nourished artificially].

The features of catch-up growth were studied, with the aid of anthropometric measurements, in 59 malnourished children, under continuous enteral or parenteral nutrition. Normal weight was reached after 4 months and normal height after 10 months. Protein compartment was normalized after 4 months; so was the fat tissue compartment, for which, however, further increase occurred up to the 6th month. This evolutive profile, observed under artificial nutrition, does not differ from the catch-up observed under spontaneous oral feeding. The excess in fatty mass partially accounts for the high energetic cost, half reduced however in artificial feeding. The authors emphasize the risk of excessive energetic intake in artificial feeding and underline the importance of anthropometric monitoring of the lean body in the modulation of the intake.

Adolescent↗
PubMed2006

Evolution of branched regulatory genetic pathways: directional selection on pleiotropic loci accelerates developmental system drift.

Developmental systems are regulated by a web of interacting loci. One common and useful approach in studying the evolution of development is to focus on classes of interacting elements within these systems. Here, we use individual-based simulations to study the evolution of traits controlled by branched developmental pathways involving three loci, where one locus regulates two different traits. We examined the system under a variety of selective regimes. In the case where one branch was under stabilizing selection and the other under directional selection, we observed "developmental system drift": the trait under stabilizing selection showed little phenotypic change even though the loci underlying that trait showed considerable evolutionary divergence. This occurs because the pleiotropic locus responds to directional selection and compensatory mutants are then favored in the pathway under stabilizing selection. Though developmental system drift may be caused by other mechanisms, it seems likely that it is accelerated by the same underlying genetic mechanism as that producing the Dobzhansky-Muller incompatibilities that lead to speciation in both linear and branched pathways. We also discuss predictions of our model for developmental system drift and how different selective regimes affect probabilities of speciation in the branched pathway system.

Animals↗
PubMed2002

Evolution and spread of antibiotic resistance.

Antibiotic resistance is a clinical and socioeconomical problem that is here to stay. Resistance can be natural or acquired. Some bacterial species, such as Pseudomonas aeruginosa, show a high intrinsic resistance to a number of antibiotics whereas others are normally highly antibiotic susceptible such as group A streptococci. Acquired resistance evolve via genetic alterations in the microbes own genome or by horizontal transfer of resistance genes located on various types of mobile DNA elements. Mutation frequencies to resistance can vary dramatically depending on the mechanism of resistance and whether or not the organism exhibits a mutator phenotype. Resistance usually has a biological cost for the microorganism, but compensatory mutations accumulate rapidly that abolish this fitness cost, explaining why many types of resistances may never disappear in a bacterial population. Resistance frequently occurs stepwise making it important to identify organisms with low level resistance that otherwise may constitute the genetic platform for development of higher resistance levels. Self-replicating plasmids, prophages, transposons, integrons and resistance islands all represent DNA elements that frequently carry resistance genes into sensitive organisms. These elements add DNA to the microbe and utilize site-specific recombinases/integrases for their integration into the genome. However, resistance may also be created by homologous recombination events creating mosaic genes where each piece of the gene may come from a different microbe. The selection with antibiotics have informed us much about the various genetic mechanisms that are responsible for microbial evolution.

Animals↗
PubMed2026

Balancing under constraint: Structural insights into norovirus evolution and antigenic innovation.

Norovirus is the leading cause of acute viral gastroenteritis worldwide. While genomic studies have revealed its diversity and evolutionary patterns, the structural mechanisms driving viral adaptation remain poorly understood. Here, we establish a comprehensive structural database of norovirus VP1 P-domains across nine genogroups (GI-GIX) through large-scale AlphaFold2 predictions. By integrating phylogenetic analysis of VP1 sequences and structures, we demonstrate that sequence and structural evolution show overall concordance under purifying selection, yet significant local discrepancies reveal distinct patterns of convergent evolution shaped by structural constraints and functional divergence. Focusing on the predominant GII.4 genotype, we found that compared to near-full-genome and nucleotide trees, only the VP1 amino acid tree reliably clustered GII.4 variants in chronological order as monophyletic groups. We further identify a hierarchical evolutionary strategy: positive selection may drive structural hypervariability in major antigenic epitopes D and C for immune escape, with epitope D exhibiting pronounced structural flexibility that complicates its structural characterization, whereas coevolutionary analysis uncovers a broad network of compensatory interactions spanning multiple epitopes, with striking enrichment in epitope A. These epitopes exhibited a pattern of "sequence plasticity with structural conservation", maintained by coevolutionary constraints that preserve conformational integrity. Together, these findings suggest that norovirus vaccine strategies targeting the structurally conserved conformations of epitopes A and G could overcome the limitations of traditional strain-specific approaches, offering a pathway toward broad protection against evolving viral diversity.

Norovirus↗
PubMed2026

Viral mimicry escape as a necessary feature of malignant transformation.

Malignant transformation is driven by disruption of pathways regulating proliferation and cell fate, but these same disruptions can create a collateral vulnerability: loss of transcriptional and epigenetic control over transposable elements and other normally silenced genomic regions. Consequently, emerging cancer cells can accumulate transposable element-derived and other endogenous immunogenic nucleic acids capable of triggering antiviral responses, a process termed viral mimicry. Increasing evidence indicates that viral mimicry can eliminate precancerous cells and shape tumour evolution, positioning it as an intrinsic tumour-suppressive mechanism. Here we highlight how cancer-associated changes in DNA methylation, histone modifications, splicing and RNA processing can lead to the presence of immunogenic nucleic acids that can activate viral mimicry pathways. We outline how cancer cells suppress viral mimicry, including compensatory epigenetic repression, RNA editing, nucleic acid decay and dampening of interferon signalling to enable cancer cell growth. Finally, we highlight the evidence suggesting that escaping viral mimicry is a fundamental process for cancer initiation and progression, and suggest that viral mimicry escape is necessary for cancer transformation and a therapeutic target in combination with immunotherapies. By framing viral mimicry escape as a necessary part of cancer transformation, this Review provides a unifying conceptual model for its translational exploitation.

Journal Article↗
PubMed2000

Evolutionary reversals during viral adaptation to alternating hosts.

Experimental adaptation of the bacteriophage phiX174 to a Salmonella host depressed its ability to grow on the traditional Escherichia host, whereas adaptation to Escherichia did not appreciably affect growth on Salmonella. Continued host switching consistently exhibited this pattern. Growth inhibition on Escherichia resulted from two to three substitutions in the major capsid gene. When these phages were forced to grow again on Escherichia, fitness recovery occurred predominantly by reversions at these same sites, rather than by second-site compensatory changes, the more frequently observed mechanism in most microbial systems. The affected residues lie on the virion surface and they alter attachment efficiency, yet they occur in a region distinct from a putative binding region previously identified from X-ray crystallography. These residues not only experienced high rates of evolution in our experiments, but also exhibited high levels of radical amino acid variation among phiX174 and its known relatives, consistent with a history of adaptation involving these sites.

Adaptation, Physiological↗
PubMed2005

Temporal evolution of mouse striatal gene expression following MPTP injury.

The gradual loss of striatal dopamine and dopaminergic neurons residing in the substantia nigra (SN) causes parkinsonism characterized by slow, halting movements, rigidity, and resting tremor when neuronal loss exceeds a threshold of approximately 80%. It is estimated that there is extensive compensation for several years prior to symptom onset, during which vulnerable neurons asynchronously die. Recent evidence would argue that much of the compensatory response of the nigrostriatal system is multimodal including both pre-synaptic and striatal mechanisms. Although parkinsonism may have multiple causes, the classic syndrome, Parkinson's disease (PD), is frequently modeled in small animals by repeated administration of the selective neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Because the MPTP model of PD recapitulates many of the known behavioral and pathological features of human PD, we asked whether the striatal cells of mice treated with MPTP in a semi-chronic paradigm enact a transcriptional program that would help elucidate the response to dopamine denervation. Our findings reveal a time-dependent dysregulation in the striatum of a set of genes whose products may impact both the viability and ability to communicate of dopamine neurons in the SN.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2003

Reductive genome evolution in Buchnera aphidicola.

We have sequenced the genome of the intracellular symbiont Buchnera aphidicola from the aphid Baizongia pistacea. This strain diverged 80-150 million years ago from the common ancestor of two previously sequenced Buchnera strains. Here, a field-collected, nonclonal sample of insects was used as source material for laboratory procedures. As a consequence, the genome assembly unveiled intrapopulational variation, consisting of approximately 1,200 polymorphic sites. Comparison of the 618-kb (kbp) genome with the two other Buchnera genomes revealed a nearly perfect gene-order conservation, indicating that the onset of genomic stasis coincided closely with establishment of the symbiosis with aphids, approximately 200 million years ago. Extensive genome reduction also predates the synchronous diversification of Buchnera and its host; but, at a slower rate, gene loss continues among the extant lineages. A computational study of protein folding predicts that proteins in Buchnera, as well as proteins of other intracellular bacteria, are generally characterized by smaller folding efficiency compared with proteins of free living bacteria. These and other degenerative genomic features are discussed in light of compensatory processes and theoretical predictions on the long-term evolutionary fate of symbionts like Buchnera.

Base Sequence↗
PubMed2004

Non-homogenized ITS regions in the parasitic nematode Cooperia oncophora.

Here, the validity of the assumption of concerted evolution of ribosomal regions in larval and adult Cooperia oncophora was assessed. In each of 4 individuals of this parasitic nematode, at least 78% of the sequences comprised different ITS variants. This implies that concerted evolution is not acting, which is corroborated by the scarcity of signatures of gene conversion and recombination. Mis-incorporation of nucleotides and illegitimate PCR-induced recombination turned out to be unlikely, and positions with substantial frequencies of alternative nucleotides corresponded to ambiguous positions in published ITS2 sequences of this and other Cooperia species based on direct sequencing. The ITS regions of each individual C. oncophora displayed a significant excess of unique mutations in agreement with expansion of the ribosomal gene family. Interesting corollaries of the inferred size changes of this gene family are genomic rearrangements that occur during larval development such as multiple rounds of endoduplication (in Rhabditidae), chromatin diminution (in Ascaris), and non-compensatory mutations on the secondary structure of the ITS2. It is yet unknown which process is important in trichostrongylids. Finally, although it can not be rigorously assessed in Cooperia, the ITS polymorphisms can readily be envisioned to affect phylogenetic reconstructions of closely related nematodes.

Animals↗