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PubMed2005

Foot-and-mouth disease virus evolution: exploring pathways towards virus extinction.

Foot-and-mouth disease virus (FMDV) is genetically and phenotypically variable. As a typical RNA virus, FMDV follows a quasispecies dynamics, with the many biological implications of such a dynamics. Mutant spectra provide a reservoir of FMDV variants, and minority subpopulations may become dominant in response to environmental demands or as a result of statistical fluctuations in population size. Accumulation of mutations in the FMDV genome occurs upon subjecting viral populations to repeated bottleneck events and upon viral replication in the presence of mutagenic base or nucleoside analogs. During serial bottleneck passages, FMDV survive during extended rounds of replication maintaining low average relative fitness, despite linear accumulation of mutations in the consensus genomic sequence. The critical event is the occurrence of a low frequency of compensatory mutations. In contrast, upon replication in the presence of mutagens, the complexity of mutant spectra increases, apparently no compensatory mutations can express their fitness-enhancing potential, and the virus can cross an error threshold for maintenance of genetic information, resulting in virus extinction. Low relative fitness and low viral load favor FMDV extinction in cell culture. The comparison of the molecular basis of resistance to extinction upon bottleneck passage and extinction by enhanced mutagenesis is providing new insights in the understanding of quasispecies dynamics. Such a comparison is contributing to the development of new antiviral strategies based on the transition of viral replication into error catastrophe.

Biological Evolution↗

PubMed2000

Why move the eyes if we can move the head?

To see while moving is a very basic and integrative sensorimotor function in vertebrates. To maintain visual acuity, the oculomotor system provides efficient compensatory eye movements for head and visual field displacements. Other types of eye movement allow the selection of new visual targets and binocular vision and stereopsis. Motor and premotor neuronal circuits involved in the genesis and control of eye movements are briefly described. The peculiar properties and robust biomechanics of the oculomotor system have allowed it to survive almost unchanged through vertebrate evolution.

Animals↗

PubMed2005

Evasion of Toll-like receptor 5 by flagellated bacteria.

Toll-like receptor 5 (TLR5) recognizes an evolutionarily conserved site on bacterial flagellin that is required for flagellar filament assembly and motility. The alpha and epsilon Proteobacteria, including the important human pathogens Campylobacter jejuni, Helicobacter pylori, and Bartonella bacilliformis, require flagellar motility to efficiently infect mammalian hosts. In this study, we demonstrate that these bacteria make flagellin molecules that are not recognized by TLR5. We map the site responsible for TLR5 evasion to amino acids 89-96 of the N-terminal D1 domain, which is centrally positioned within the previously defined TLR5 recognition site. Salmonella flagellin is strongly recognized by TLR5, but mutating residues 89-96 to the corresponding H. pylori flaA sequence abolishes TLR5 recognition and also destroys bacterial motility. To preserve bacterial motility, alpha and epsilon Proteobacteria possess compensatory amino acid changes in other regions of the flagellin molecule, and we engineer a mutant form of Salmonella flagellin that evades TLR5 but retains motility. These results suggest that TLR5 evasion is critical for the survival of this subset of bacteria at mucosal sites in animals and raise the intriguing possibility that flagellin receptors provided the selective force to drive the evolution of these unique subclasses of bacterial flagellins.

Amino Acid Sequence↗

PubMed2006

Cyto-nuclear epistasis: two-locus random genetic drift in hermaphroditic and dioecious species.

We report the findings of our theoretical investigation of the effect of random genetic drift on the covariance of identity-by-descent (ibd) of nuclear and cytoplasmic genes. The covariance in ibd measures of the degree to which cyto-nuclear gene combinations are heritable, that is, transmitted together from parents to offspring. We show how the mating system affects the covariance of ibd, a potentially important aspect of host-pathogen or host-symbiont coevolution. The magnitude of this covariance influences the degree to which the evolution of apparently neutral cytoplasmic genes, often used in molecular phylogenetics, might be influenced by selection acting on unlinked nuclear genes. To the extent that cyto-nuclear gene combinations are inherited together, genomic conflict is mitigated and intergenomic transfer it facilitated, because genes in both organelle and nuclear genomes share the same evolutionary fate. The covariance of ibd also affects the rate at which cyto-nuclear epistatic variance is converted to additive variance necessary for a response to selection. We find that conversion is biased in species with separate sexes, so that the increment of additive variance added to the nuclear genome exceeds that added to the cytoplasmic genome. As a result, the host might have an adaptive advantage in a coevolutionary arms race with vertically (maternally) transmitted pathogens. Similarly, the nuclear genome could be a source of compensatory mutations for its organellar genomes, as occurs in cytoplasmic male sterility in some plant species. We also discuss the possibility that adaptive cytoplasmic elements, such as favorable mitochondrial mutations or endosymbionts (e.g., Wolbachia), have the potential to release heritable nuclear variation as they sweep through a host population, supporting the view that cytoplasmic introgression plays an important role in adaptation and speciation.

Alleles↗

PubMed1976

The differential development of the hominid pelvis.

The peculiarly shaped hominid pelvis represents the total response to the diverse forces which have moulded its structure, these being requirements for efficient bipedalism and parturition. In some respects the structural requirements of these unrelated functions have been in conflict. In these instances the morphological response to the dominant requirement, viz. bipedalism, is clearly discernible, while the changes subserving the needs of parturition are seen as compensatory modifications, the greater emphasis of which is responsible, in part, for pelvic sexual dimorphism in the female. Total pelvic architecture is thus a mosaic constituted by the aggregate of differential responses to different functional goals.

Adolescent↗

PubMed1998

Kinematics of aquatic and terrestrial prey capture in Terrapene carolina, with implications for the evolution of feeding in cryptodire turtles.

Studies of aquatic prey capture in vertebrates have demonstrated remarkable convergence in kinematics between diverse vertebrate taxa. When feeding in water, most vertebrates employ large-amplitude hyoid depression to expand the oral cavity and suck in water along with the prey. In contrast, vertebrates feeding on land exhibit little or no hyoid depression. In this study we compared the kinematics of terrestrial and aquatic prey capture within one species of turtle, Terrapene carolina, in order to determine whether an individual species can modulate the magnitude of hyoid depression between air and water. High-speed video (250 frames per second) showed that hyoid depression was over three times greater in aquatic than in terrestrial feedings, indicating that T. carolina is able to modulate hyoid depression magnitude depending on the medium in which feeding occurs. In addition, we observed medium-dependent modulation of hyoid depression in another turtle, Heosemys grandis, and large-amplitude hyoid depression during aquatic feeding in Kinosternon leucostomum, Platysternon megacephalum, and juvenile Chelydra serpentina. In all of these turtles, hyoid depression produced oral cavity expansion during aquatic feeding, but the earthworm prey were never sucked toward the predators. Prey were captured by neck extension (ram feeding), and we conclude that the function of hyoid depression during aquatic feeding in cryptodire turtles is to prevent the forward motion of the predator from pushing the prey away (compensatory suction). Aquatic feeding is probably the primitive condition for all extant turtles, and thus terrestrial feeding in T. carolina and other turtles is a secondarily derived characteristic. We conclude from this historical pattern that it is not appropriate to use extant turtles in attempts to reconstruct the terrestrial feeding mechanisms of primitive amniotes.

Animals↗

PubMed2003

The evolution of sexual size dimorphism in the house finch. V. Maternal effects.

The phenotype of a mother and the environment that she provides might differentially affect the phenotypes of her sons and daughters, leading to change in sexual size dimorphism. Whereas these maternal effects should evolve to accommodate the adaptations of both the maternal and offspring generations, the mechanisms by which this is accomplished are rarely known. In birds, females adjust the onset of incubation (coincident with the first egg or after all eggs are laid) in response to the environment during breeding, and thus, indirectly, determine the duration of offspring growth. In the two house finch (Carpodacus mexicanus) populations that breed at the extremes of the species' distribution (Montana and Alabama), females experience highly distinct climatic conditions during nesting. We show that in close association with these conditions, females adjusted jointly the onset of incubation and the sequence in which they produced male and female eggs and consequently modified the growth of sons and daughters. The onset of incubation in newly breeding females closely tracked ambient temperature in a pattern consistent with the maintenance of egg viability. Because of the very different climates in Montana and Alabama, females in these populations showed the opposite patterns of seasonal change in incubation onset and the opposite sex bias in egg-laying order. In females with breeding experience, incubation onset and sex bias in laying order were closely linked regardless of the climatic variation. In nests in which incubation began with the onset of egg laying, the first-laid eggs were mostly females in Montana, but mostly males in Alabama. Because in both populations, male, but not female, embryos grew faster when exposed to longer incubation, the sex-bias produced highly divergent sizes of male and female juveniles between the populations. Overall, the compensatory interaction between the onset of incubation and the sex-biased laying order achieved a compromise between maternal and offspring adaptations and contributed to rapid morphological divergence in sexual dimorphism between populations of the house finch breeding at the climatic extremes of the species range.

Animals↗

PubMed1995

Experimental atrophy/hypertrophy complex (AHC) of the liver: portal vein, but not bile duct obstruction, is the main driving force for the development of AHC in the rat.

BACKGROUND/AIMS: Patients with lobar or segmental impairment of bile flow or of portal venous blood flow frequently develop considerable atrophy of the area involved, followed by compensatory hypertrophy/hyperplasia of the non-affected parts. This configuration is termed atrophy/hypertrophy complex of the liver. METHODS: In order to analyze the relative contributions of bile duct and portal vein obstruction in the pathogenesis of atrophy/hypertrophy complex, we developed a rat model with selective bile duct and/or portal vein ligation of the anterior liver lobes, representing about two thirds of the liver mass. Evolution of total body weights and weights of the different liver lobes were determined, and morphometry and functional scintigraphy (hepatoiodida scanning) were performed immediately after ligation and at 30 h, 4, 8 and 28 days postoperatively. RESULTS: The major findings were: 28 days after biliary and/or portal ligation there was no difference between the body weights of all animals, all ligated animals having compensated an initial body weight loss. Total liver weight remained constant during the whole observation period, while atrophy of the anterior and hypertrophy/hyperplasia of the posterior lobes occurred. A significant atrophy/hypertrophy complex developed only after selective portal ligation, but not after selective biliary ligation. Morphometrically analyzed histologic changes after selective biliary ligation were reversible, whereas in portally ligated liver lobes a progressive parenchymal destruction and involution with subsequent impairment of hepatic function of the concerned lobe were observed. CONCLUSIONS: The present findings indicate that impairment of portal venous flow is the major driving force for the development of lobar atrophy in the rat and that atrophy/hypertrophy complex can be produced in a rodent model.

Animals↗

PubMed1987

Ecological compensation--a complication for testing life-history theory.

Mortality, growth and birth rates cannot vary independently in stable populations, environmental change of one variable must be accompanied by compensatory variation of another. Ecological compensation is recognized if the stable populations are genetically identical. Ecological compensation, if it operates, constrains the direction of evolutionary change, and predictions that ignore it may be in error.

Adaptation, Physiological↗

PubMed2005

Emergence and evolution of enfuvirtide resistance following long-term therapy involves heptad repeat 2 mutations within gp41.

The objective of this study was to track the evolution of sequence changes in both the heptad region 1 (HR1) and HR2 domains of gp41 associated with resistance to enfuvirtide (ENF) in a patient cohort receiving long-term ENF treatment. We studied 17 highly antiretroviral agent-experienced patients receiving long-term ENF treatment with virological rebound or a lack of suppression. Sixty-two samples obtained after between 5 and 107 weeks of ENF therapy were analyzed. Baseline samples from 15 of these 17 patients were available for analysis. Viruses from five samples from four patients were also sequenced after the cessation of ENF therapy. Drug susceptibilities were assessed by a pseudotype virus reporter assay. We identified HR1 and HR2 sequence changes over time in relation to the baseline sequences. Mutations in HR1 (amino acids 36 to 45) were noted in all cases, including previously unreported changes N42Q/H and N43Q. In addition to a range of HR2 sequence changes at polymorphic sites, isolates from 6 of 17 (35%) patients developed an S138A substitution in the HR2 domain at least 8 weeks after the start of ENF treatment and also subsequent to the first emergence of HR1 mutations. In most, but not all, cases the S138A mutation accompanied HR1 mutations at position 43. Molecular modeling demonstrates the close proximity of S138A with amino acids 40 and 45 in HR1. Of note, isolates in samples available from four patients demonstrated the loss of both the HR1 and the S138A HR2 mutations following the cessation of therapy. We show that the S138A HR2 mutation increased the level of resistance by approximately threefold over that conferred by the HR1 mutation N43D. Continual evolution of HR1 in the domain from amino acids 36 to 45 was observed during long-term ENF therapy. We have identified, for the first time, an ENF resistance-associated HR2 mutation, S138A, which appeared in isolates from 6 of 17 patients with virological failure and demonstrated its potential to contribute to drug resistance. We propose that this represents a possible secondary and/or compensatory mutation, particularly when it coexists with mutations at position 43 in HR-1.

Amino Acid Sequence↗

PubMed1997

Structural comparisons of muscle and nonmuscle actins give insights into the evolution of their functional differences.

Actin is a highly conserved protein although many isoforms exist. In vertebrates and insects the different actin isoforms can be grouped by their amino acid sequence and tissue-specific gene expression into muscle and nonmuscle actins, suggesting that the different actins may have a functional significance. We ask here whether atomic models for G- and F-actins may help to explain this functional diversity. Using a molecular graphics program we have mapped the few amino acids that differ between isoactins. A small number of residues specific for muscle actins are buried in internal positions and some present a remarkable organization. Within the molecule, the replacements observed between muscle and nonmuscle actins are often accompanied by compensatory changes. The others are dispersed on the protein surface, except for a cluster located at the N-terminus which protrudes outward. Only a few of these residues specific for muscle actins are present in known ligand binding sites except the N-terminus, which has a sequence specific for each isoactin and is directly implicated in the binding to myosin. When we simulated the replacements of side chains of residues specific for muscle actins to those specific for nonmuscle actins, the N-terminus appears to be less compact and more flexible in nonmuscle actins. This would represent the first conformational grounds for proposing that muscle and nonmuscle actins may be functionally distinguishable. The rest of the molecule is very similar or identical in all the actins, except for a possible higher internal flexibility in muscle actins. We propose that muscle actin genes have evolved from genes of nonmuscle actins by substitutions leading to some conformational changes in the protruding N-terminus and the internal dynamics of the main body of the protein.

Actins↗

PubMed1989

Molecular evolution of the small subunit of ribulose bisphosphate carboxylase: nucleotide substitution and gene conversion.

The nucleotide sequences encoding the mature portion of 31 ribulose 1.5-bisphosphate carboxylase small subunit (SSU) genes from 17 genera of plants, green algae and cyanobacteria were examined. Among the 465 pairwise sequence comparisons, SSU multigene family members within the same species were more similar to each other in nonsynonymous or replacement nucleotide substitutions (RNS) than they were to SSU sequences in any other organism. The concerted evolution of independent SSU gene lineages within closely related plant species suggests that homogenization of RNS positions has occurred at least once in the life of each genus. The rate of expected RNS among mature SSU sequences was calculated to be 1.25 X 10(-9)/site/yr for the first 70 million years (MY) of divergence with a significant slowing to 0.13 X 10(-9)/site/yr for the next 1,400 MY. The data suggest that mature SSU sequences do not accumulate more than 20% differences in the RNS positions without compensatory changes in other components of this enzyme system. During the first 70 MY of divergence between species, the rate of expected synonymous or silent nucleotide substitutions (SNS) is approximately 6.6 X 10(-9)/site/yr. This is five times the RNS rate and is similar to the silent rate observed in animals. In striking contrast, SNS and RNS do not show this correlation among SSU gene family members within a species. A mechanism involving gene conversion within the exons followed by selection for biased gene conversion products with conservation of RNS positions and divergence of SNS positions is discussed. A SSU gene tree based on corrected RNS for 31 SSU sequences is presented and agrees well with a species tree based on morphological and cytogenetic traits for the 17 genera examined. SSU gene comparisons may be useful in predicting phylogenetic relationships and in some cases divergence times of various plant, algal and cyanobacterial species.

Amino Acid Sequence↗

PubMed1982

[Dynamic functional changes in the respiratory system in acquired heart defects].

One hundred forty eight patients were examined, 56 of them followed up dynamically. The following indices were determined--external respiration, diffuse capacity of lungs and its components, acid-base state and blood gases, functional and true intrapulmonary shunts, etc. The results revealed that the dynamic functional disorders in respiratory system in the acquired valvular diseases are reversible, to a great extent, after the application of a complex therapy. Most significant is the dynamics of the recovery in stage IIA of cardiac insufficiency and the changes in DLCO, SS and DM, VC, MRV, RQ, DS%RC. The disturbed respiratory function in stage I of cardiac insufficiency is almost completely restored, whereas in stage IIB--the recovery processes are less manifested, conditioned by the reduced compensatory mechanism and the advancing of irreversible pathomorphological changes. The changes in DLCO, SS are the most sensitive ones, being the earliest to manifest, even before the manifestation of the clinical symptoms and could aid the early functional diagnostics of the acquired valvular defects. The dynamic follow up of the functional changes in the respiratory system enables us to assess more thoroughly the results from the treatment, evolution and prognosis of the acquired valvular diseases.

Acid-Base Equilibrium↗

PubMedDate not supplied

Luteal phase immunosuppression and meat eating.

Immunosuppression during pregnancy makes the mother vulnerable to pathogens. Because meat is the principal source of ingestible pathogens, pregnancy raises the costs of meat eating. Natural selection has crafted a mechanism involving changes in nausea susceptibility and olfactory perception that reduces meat consumption during pregnancy. Evidence is presented showing that the luteal phase is marked by both immunosuppression and changes in nausea susceptibility and olfaction; meat consumption may be reduced during this period, suggesting a mechanism similar to pregnancy sickness. Constraints on compensatory increases in meat consumption outside of the luteal phase explain why women eat less meat than men. Meat is the principal target of acquired aversions. Women possess more aversions than men, suggesting that prophylactic mechanisms sometimes result in longstanding dietary changes. Reproductive immunosuppression explains many aspects of dietary behavior and sheds light on factors that may have contributed to gender-based divisions of labor during hominid evolution.

Animals↗

PubMed2004

Dikaryons of the basidiomycete fungus Schizophyllum commune: evolution in long-term culture.

The impact of ploidy on adaptation is a central issue in evolutionary biology. While many eukaryotic organisms exist as diploids, with two sets of gametic genomes residing in the same nucleus, most basidiomycete fungi exist as dikaryons in which the two genomes exist in separate nuclei that are physically paired and that divide in a coordinated manner during hyphal extension. To determine if haploid monokaryotic and dikaryotic mycelia adapt to novel environments under natural selection, we serially transferred replicate populations of each ploidy state on minimal medium for 18 months (approximately 13,000 generations). Dikaryotic mycelia responded to selection with increases in growth rate, while haploid monokaryotic mycelia did not. To determine if the haploid components of the dikaryon adapt reciprocally to one another's presence over time, we recovered the intact haploid components of dikaryotic mycelia at different time points (without meiosis) and mated them with nuclei of different evolutionary histories. We found evidence for coadaptation between nuclei in one dikaryotic line, in which a dominant deleterious mutation in one nucleus was followed by a compensatory mutation in the other nucleus; the mutant nuclei that evolved together had the best overall fitness. In other lines, nuclei had equal or higher fitness when paired with nuclei of other histories, indicating a heterozygote advantage. To determine if genetic exchange occurs between the two nuclei of a dikaryon, we developed a 24-locus genotyping system based on single nucleotide polymorphisms to monitor somatic exchange. We observed genetic exchange and recombination between the nuclei of several different dikaryons, resulting in genotypic variation in these mitotic cell lineages.

Base Sequence↗

PubMed2004

Schizophrenia-an evolutionary enigma?

The term 'schizophrenia' refers to a group of disorders that have been described in every human culture. Two apparently well established findings have corroborated the need for an evolutionary explanation of these disorders: (1) cross-culturally stable incidence rates and (2) decreased fecundity of the affected individuals. The rationale behind this relates to the evolutionary paradox that susceptibility genes for schizophrenia are obviously preserved in the human genepool, despite fundamental reproductive disadvantages associated with the disorders. Some researchers have therefore proposed that a compensatory advantage must exist in people who are carriers of these genes or in their first-degree relatives. Such advantages were hypothesised to be outside the brain (e.g. greater resistance against toxins or infectious diseases), or within the social domain (e.g. schizotypal shamans, creativity). More specifically, T.J. Crow has suggested an evolutionary theory of schizophrenia that relates the disorders to an extreme of variation of hemispheric specialisation and the evolution of language due to a single gene mutation located on homologous regions of the sex chromosomes. None of the evolutionary scenarios does, however, fully account for the diversity of the symptomatology, nor does any one hypothesis acknowledge the objection that the mere prevalence of a disorder must not be confused with adaptation. In the present article, I therefore discuss the evolutionary hypotheses of schizophrenia, arguing that a symptom-based approach to psychotic disorders in evolutionary perspective may improve upon the existing models of schizophrenia.

Adaptation, Biological↗

PubMed2000

Disaptation and recovery in the evolution of Antarctic fishes.

The radiation of notothenioid fishes provides an excellent system to explore issues of evolution and adaptation. Most studies emphasize adaptation to the extreme Antarctic environment; however, recent work provides cogent examples of disaptation or evolutionary loss of function. The nature and extent of regressive change is revealed by subsequent adaptive recovery. Ancestral notothenioids were benthic but some became secondarily pelagic through the retention of larval characters. Paedomorphosis has produced detrimental changes in lateral-line sensory systems that have been made good by compensatory adaptation. In the icefish family, compensatory adaptation has followed the loss of the oxygen-binding pigments haemoglobin and myoglobin.

Journal Article↗

PubMed2003

Patterns of linkage disequilibrium in mitochondrial DNA of 16 ruminant populations.

Mitochondrial DNA (mtDNA) is a widely employed molecular tool in phylogeography, in the inference of human evolutionary history, in dating the domestication of livestock and in forensic science. In humans and other vertebrates the popularity of mtDNA can be partially attributed to an assumption of strict maternal inheritance, such that there is no recombination between mitochondrial lineages. The recent demonstration that linkage disequilibrium (LD) declines as a function of distance between polymorphic sites in hominid mitochondrial genomes has been interpreted as evidence of recombination between mtDNA haplotypes, and hence nonclonal inheritance. However, critics of mtDNA recombination have suggested that this association is an artefact of an inappropriate measure of LD or of sequencing error, and subsequent studies of other populations have failed to replicate the initial finding. Here we report the analysis of 16 ruminant populations and present evidence that LD significantly declines with distance in five of them. A meta-analysis of the data indicates a nonsignificant trend of LD declining with distance. Most of the earlier criticisms of patterns between LD and distance in hominid mtDNA are not applicable to this data set. Our results suggest that either ruminant mtDNA is not strictly clonal or that compensatory selection has influenced patterns of variation at closely linked sites within the mitochondrial control region. The potential impact of these processes should be considered when using mtDNA as a tool in vertebrate population genetic, phylogenetic and forensic studies.

Animals↗