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Evolutionary aspects of oncogenic herpesviruses.

Several of the gamma-herpesviruses are known to have cellular transforming and oncogenic properties. The genomes of eight distinct gamma-herpesviruses have been sequenced, and the resulting database of information has enabled the identification of genetic similarities and differences between evolutionarily closely related and distant viruses of the subfamily and between the gamma-herpesviruses and other members of the herpesvirus family. The recognition of coincident loci of genetic divergence between individual gamma-herpesviruses and the identification of novel genes and cellular gene homologues in these genomic regions has delineated a subset of genes that are likely to contribute to the unique biological properties of these viruses. These genes, together with gamma-herpesvirus conserved genes not found in viruses outside the family, might be responsible for virus specific pathogenicity and pathogenic effects, such as viral associated neoplasia, characteristic of the subfamily. The presence of the gamma-herpesvirus major divergent genomic loci and the apparent increased mutational frequencies of homologous genes (where they occur) within these regions, indicates that these loci possess particular features that drive genetic divergence. Whatever the mechanisms underlying this phenomenon, it potentially provides the basis for the relatively rapid adaptation and evolution of gamma-herpesviruses and the diversity of biological and pathogenic properties.

Cell Transformation, Viral↗

Adaptive denoising and multiscale detection of the V wave in brainstem auditory evoked potentials.

This paper describes a wavelet-transform-based system for the V wave identification in brainstem auditory evoked potentials (BAEP). The system combines signal denoising and rule-based localization modules. The signal denoising module has the potential of effective noise reduction after signal averaging. It analyses adaptively the evolution of the wavelet transform maxima across scales. The singularities of the signal create wavelet maxima with different properties from those of the induced noise. A non-linear filtering process implemented with a neural network extracts out the noise-induced maxima. The filtered wavelet details are subsequently analysed by the rule-based localization module for the automatic identification of the V wave. In the first phase, it implements a set of statistical observations as well as heuristic criteria used by human experts in order to classify the IV-V complex. At the second phase, using a multiscale focusing algorithm, the IV and V waves are positioned on the BAEP signal. Our experiments revealed that the system provides accurate results even for signals exhibiting unclear IV-V complexes.

Auditory Threshold↗

A wing expressed sequence tag resource for Bicyclus anynana butterflies, an evo-devo model.

BACKGROUND: Butterfly wing color patterns are a key model for integrating evolutionary developmental biology and the study of adaptive morphological evolution. Yet, despite the biological, economical and educational value of butterflies they are still relatively under-represented in terms of available genomic resources. Here, we describe an Expression Sequence Tag (EST) project for Bicyclus anynana that has identified the largest available collection to date of expressed genes for any butterfly. RESULTS: By targeting cDNAs from developing wings at the stages when pattern is specified, we biased gene discovery towards genes potentially involved in pattern formation. Assembly of 9,903 ESTs from a subtracted library allowed us to identify 4,251 genes of which 2,461 were annotated based on BLAST analyses against relevant gene collections. Gene prediction software identified 2,202 peptides, of which 215 longer than 100 amino acids had no homology to any known proteins and, thus, potentially represent novel or highly diverged butterfly genes. We combined gene and Single Nucleotide Polymorphism (SNP) identification by constructing cDNA libraries from pools of outbred individuals, and by sequencing clones from the 3' end to maximize alignment depth. Alignments of multi-member contigs allowed us to identify over 14,000 putative SNPs, with 316 genes having at least one high confidence double-hit SNP. We furthermore identified 320 microsatellites in transcribed genes that can potentially be used as genetic markers. CONCLUSION: Our project was designed to combine gene and sequence polymorphism discovery and has generated the largest gene collection available for any butterfly and many potential markers in expressed genes. These resources will be invaluable for exploring the potential of B. anynana in particular, and butterflies in general, as models in ecological, evolutionary, and developmental genetics.

Animals↗

Molecular signatures of adaptive introgression and selection in contact zones of closely related pine species (Pinus genus).

BACKGROUND: Natural hybridization plays a key role in shaping genetic diversity, local adaptation, and the dynamics of speciation through interspecific gene flow. Hybrid zones serve as valuable natural systems for studying these processes. In this research, we used genotypic data at thousands of nuclear SNPs to investigate genomic outcomes of hybridization and selection across three contact zones of closely related pine species including Scots pine (Pinus sylvestris L.) and dwarf mountain pine (P. mugo T.). Reference allopatric stands of parental species were used to assess introgression dynamics. RESULTS: Individuals from the hybrid zones showed distinct genetic ancestry patterns and were assigned to groups including putative pure species, first-generation hybrids, and advanced backcrosses. Genotypes of the majority of hybrids were shifted towards P. mugo ancestry. Most outlier loci were shared across all sympatric populations, although some were specific to individual contact zones. The identified outliers were mainly associated with regulatory biological processes related to phosphorylation, proteolysis, and transmembrane transport. Signatures of local adaptation varied in different genetic classes in contact zones and they were strongest in pure P. sylvestris and hybrids with a majority of P. sylvestris ancestry. The pattern suggests that it may be driven by adaptation to peat bog habitats situated outside the species’ core ecological niche. CONCLUSIONS: Our findings indicate strong selective pressure acting on multiple genes in groups of hybrids and pure Pinus sylvestris individuals across all studied hybrid zones. In contrast, the weaker signal of selection observed in individuals with P. mugo ancestry suggests that relict populations of this species, which historically spread across postglacial peat bogs, were pre-adapted to such environments. While several outlier loci were shared across different contact zones, others were unique for one of them, indicating that local environmental pressures and adaptive introgression shape the genomic composition of the populations. These results highlight the role of hybridization in generating adaptive diversity and emphasize the evolutionary significance of hybrid zones in pines.

Hybridization, Genetic↗

Molecular population genetics of accessory gland protein genes and testis-expressed genes in Drosophila mojavensis and D. arizonae.

Molecular population genetic investigation of Drosophila male reproductive genes has focused primarily on melanogaster subgroup accessory gland protein genes (Acp's). Consistent with observations from male reproductive genes of numerous taxa, Acp's evolve more rapidly than nonreproductive genes. However, within the Drosophila genus, large data sets from additional types of male reproductive genes and from different species groups are lacking. Here we report findings from a molecular population genetics analysis of male reproductive genes of the repleta group species, Drosophila arizonae and D. mojavensis. We find that Acp's have dramatically higher average pairwise Ka/Ks (0.93) than testis-enriched genes (0.19) and previously reported melanogaster subgroup Acp's (0.42). Overall, 10 of 19 Acp's have Ka/Ks > 1 either in nonpolarized analyses or in at least one lineage of polarized analyses. Of the nine Acp's for which outgroup data were available, average Ka/Ks was considerably higher in D. mojavensis (2.08) than in D. arizonae (0.87). Contrasts of polymorphism and divergence suggest that adaptive protein evolution at Acp's is more common in D. mojavensis than in D. arizonae.

Animals↗

Molecular research and the control of Chagas disease vectors.

Chagas disease control initiatives are yielding promising results. Molecular research has helped successful programs by identifying and characterizing introduced vector populations and by defining intervention targets accurately. However, researchers and health officials are facing new challenges throughout Latin America. Native vectors persistently reinfest insecticide-treated households, and sylvatic triatomines maintain disease transmission in humid forest regions (including Amazonia) without colonizing human dwellings. In these scenarios, fine-scale vector studies are essential to define epidemiological risk patterns and clarify the involvement of little-known triatomine taxa in disease transmission. These eco-epidemiological investigations, as well as the planning and monitoring of control interventions, rely by necessity on accurate taxonomic judgments. The problems of cryptic speciation and phenotypic plasticity illustrate this need--and how molecular systematics can provide the fitting answers. Molecular data analyses also illuminate basic aspects of vector evolution and adaptive trends. Here we review the applications of molecular markers (concentrating on allozymes and DNA sequencing) to the study of triatomines. We analyze the suitability, strengths and weaknesses of the various techniques for taxonomic, systematic and evolutionary investigations at different levels (populations, species, and higher taxonomic categories).

Animals↗

Pathogenesis of macrophage tropic HIV-1.

Despite numerous studies on the impact of viral diversity, human immunodeficiency virus type 1 (HIV-1)-specific immune responses and host factors on disease progression, we still do not have a firm understanding of the pathogenesis of HIV-1 infection. Rapid depletion of CD4+ T-lymphocytes has been associated with a switch in viral coreceptor usage from CCR5 to CXCR4 in approximately 40 to 50% of infected individuals. However, the majority of infected individuals who progress to AIDS harbor only CCR5-dependent (R5) viral strains. HIV-1 disease progression is associated with an enhanced tropism of R5 viral strains for cells of the monocyte/macrophage lineage (enhanced M-tropism). However, the underlying molecular mechanisms contributing to enhanced M-tropism by R5 HIV-1 strains, and how HIV-1 variants with enhanced M-tropism cause CD4+ T-cell depletion in vivo are unknown. This review examines the relationship between viral coreceptor usage, M-tropism, and pathogenicity of HIV-1. We highlight evidence supporting the hypothesis that enhanced M-tropism of R5 HIV-1 results from adaptive viral evolution, resulting in HIV-1 variants that have increased ability to utilize relatively low levels of CD4 and CCR5 expressed on macrophages. The evidence also suggests that these late-emerging, R5 viral strains have reduced sensitivity to entry inhibitors, and increased ability to cause CD4+ T-lymphocyte loss. These variants are likely to impact HIV-1 disease progression, particularly in patients who persistently harbor only R5 viral strains.

Disease Progression↗

Pathogenic diversity of Escherichia coli and the emergence of 'exotic' islands in the gene stream.

Escherichia coli is a highly adaptive bacterial species that is both a member of the commensal intestinal flora and a versatile pathogen associated with numerous types of intestinal and systemic infections in humans and other animals. The spectrum of diseases caused by E. coli is due to the acquisition of specific virulence genes harbored on plasmids, bacteriophages, or within distinct DNA segments termed pathogenicity islands (PAIs) that are absent from the genomes of commensal E. coli strains. PAIs are likely to have been transferred horizontally and may have integrated into the E. coli chromosome through bacteriophage or plasmid integration or transposition. The contribution of intergenic inheritance to the adaptation and evolution of E. coli, types of PAIs associated with different groups of pathogenic E. coli and approaches to identify unique sequence islands (USIs), some of which might confer pathogenicity, in E. coli and other bacteria are presented.

Animals↗

[Streptococcus suis bacteremia].

INTRODUCTION: Streptococcus suis infection is recognised despite it rareness as a zoonotic occupational disease in humans, and is often associated with meningitis, more rarely with bacteremia. OBSERVATION: A Streptococcus suis bacteremia occurred in a hunter and was complicated by septic shock with disseminated intravascular coagulation, rhabdomyolysis and purpura fulminans. Contamination had occurred through inoculation of a cut on the thumb when the hunter was slaughtering a wild boar. The blood cultures isolated Streptococcus suis. The patient died 36 hours after admission, despite intensive care and adapted antibiotic treatment with penicillin A and macrolide. CONCLUSION: Streptococcus suis bacteremia are uncommon but serious in humans. Despite adapted treatment, evolution may be fatal, so their conditions of occurrence must be well known by hunters and practitioners.

Anti-Bacterial Agents↗

Human natural killer cells: a comprehensive review.

The senior author of this comprehensive review observed and reported in 1969 that his lymphocytes killed allogeneic tumor cells in vitro. Some of his research associates and technicians and other healthy individuals also yielded such killer lymphocytes. The team considered pre-immunization to cancer occurring in individuals after in-family or professional exposure to patients with cancer (in an era when the concept of viral etiology of cancer was receiving major support); or that lymphocytes can acquire through blastic transformation immune reactivity to allogeneic cells anew in vitro. The phenomenon was eventually referred to as 'lymphocytes practicing Burnet's immunosurveillance.' Project site visitors of the USA NCI first viewed these observations as a matter of 'in vitro artifacts' being in opposition to strong tumor- specific cytotoxicity of tumor-bearing patients' lymphocytes recognized in the vast majority of other assays. After NCI funds were released for intramural studies on the phenomenon of non-specific cytotoxicity by lymphocytes, recipients (other than the senior author) of these NCI funds later characterized (1973-1975) the 'indiscriminately' cytotoxic lymphocyte populations as those of 'natural killer (NK) cells.' In this article, the original observations made in 1969-1971 are reviewed based on genuine material preserved by the senior author and are explained in view of recent discoveries that were not available at the time of the original observations. NK cells display a fascinating history arising first in urochordates during the cambrian explosion. At that level, NK cells protected their hosts from incompatible cell colony fusions and against intracellular, especially viral, pathogens. Since then, viruses evolved evasive maneuvers to escape NK cell attack on the infected cells. NK cells persisted after the evolution of adaptive immunity in cartilaginous fish fitting seamlessly into the new system. In mammals, NK cells assumed the role of chief arbitrators between the fetal trophoblast and maternal immune reactions to the semi-allograft fetus. Tumors induce in NK cells the same (inactivating; mediating Th2-type immunity) reactions the fetal trophoblast engenders in utero, but NK cells may overcome the host's tolerance to its tumor and kill tumor cells, especially when converted into lymphokine-activated killer (LAK) cells by molecular mediators of Th1-type immunity. The authors prepare and utilize LAK cells and IL-2 for adoptive immunotherapy of patients with metastatic melanoma and kidney carcinoma. A patient with malignant ascites due to ovarian carcinoma entered remission on LAK cell therapy. Just as dendritic cells, the major antigen presentors, may undergo malignant transformation, NK cells are also subject to transformation into FasL-producer virulent lymphoma-leukemia cells. The senior author reported in 1970 a patient with 'lymphosarcoma cell leukemia' whose circulating lymphoma cells killed indiscriminately human sarcoma and carcinoma cells. The exemplary case history of another patient with NK cell lymphoma-leukemia treated by the authors is presented.

Adult↗

[Nutritionnal epigenomics: consequences of unbalanced diets on epigenetics processes of programming during lifespan and between generations].

Epigenetic changes associated with DNA methylation and histone modifications leading to chromatin remodeling and regulation of gene expression underlie the developmental programming of obesity, type 2 diabetes, cardiovascular diseases and metabolic syndrome. This review focuses on converging data supporting the hypothesis that, in addition to "thrifty genotype" inheritance, individuals with obesity, type 2 diabetes, and metabolic syndrome (MetS) with an increased risk of cardiovascular diseases have suffered improper "epigenetic programming" during their fetal/postnatal development due to maternal inadequate nutrition and metabolic disturbances and also during their lifetime, that could even be transmitted to the next generation(s). We highlight the susceptibility of epigenetic mechanisms controlling gene expression to environmental influences due to their inherent malleability, emphasizing the participation of transposable elements and the potential role of imprinted genes during critical time windows in epigenetic programming, from the very beginning of development, throughout life. Increasing our understanding on epigenetic patterns significance and their role in development, evolution and adaptation and on small molecules (nutrients, drugs) that reverse epigenetic (in)activation should provide us with the means to "unlock" silenced (enhanced) genes, and to "convert" the obsolete human thrifty genotype into a "squandering" phenotype.

Adult↗

New aspects in mechanisms of action of corticosteroids.

In the course of evolution the adaptative mechanism arose, permitting the immune system to develop an immune response in conditions of stress. The mechanism is expressed in the growth of glucocorticosteroid-resistant lymphocyte fraction (GRLF), in the course of infectious and allergic diseases and after administration of antigens (immunization, hyposensitization). In GRLF antigen-binding lymphocytes are concentrated. This allows the conclusion that GRLF is the fraction of immunocompetent cells. A similar increase of GRLF develops in autoimmune (autoallergic) diseases. Treatment of such patients with corticosteroids suppresses inflammation only, but has no effect on the cause of damage--on GRLF. Moreover, treatment with glucocorticoids increases GRLF levels, thereby enhancing tissue damage. Thus, application of glucocorticoids, at the same time suppressing inflammation processes, stimulates the development of the autoimmune processes. This leads to formation of glucocorticoid dependence in such patients.

Animals↗

Arterial LDH, 2,3-DPG, lactate, pyruvate and acid-base balance in hypoxic albino rats of first or second generation.

Arterial acid-base balance, lactate, pyruvate, lactate dehydrogenase activity (LDH), 2,3-diphosphoglycerate content (2,3-DPG) of normoxic control rats were compared with those of rats exposed to a hypoxic normobaric environment (10% O2 in N2) within a few hours after birth (hypoxic animals of first generation or H1), and with those of rats of second generation (H2) conceived and born in the above mentioned hypoxic environment of H1 parents and maintained always in the same place since their utilization. The H1 rats showed a displacement of acid-base balance towards acidosis and an increase of lactate, pyruvate, LDH and 2,3-DPG in comparison with normoxic controls. The H2 rats showed a significant attenuation of acidosis in comparison with H1 rats; the values of lactate, pyruvate, LDH and 2,3-DPG were intermediate between those found in H1 and normoxic control rats. We believe that these results are in relation with the evolution of adaptative processes to hypoxic environment in hypoxic animals of second generation.

Acid-Base Equilibrium↗

[Heterogeneity of protein hormones in radioimmunoassay].

Radioimmunoassay measures antigenic determinants of hormonal molecules in the plasma and tissues. These estimations carried out after fractionation in biological fluids, have revealed several immunological forms of the same hormone. These immunoreactive forms may be added to already well known elements of hormonal heterogeneity: formation of aggregate, polymerisation, links to transport proteins, microheterogeneity by silent mutation. The main problem is in the relationship of the various immunoreactive forms to the same hormonal sequence. The similar immunoreactive forms of high molecular weight (big hormone) usually have low biological activity and suggest the presence of prohormone; the suggestion of prohormonal nature depends on the chronology of the incorporation of labelled leucine and enzymatic transformation of prohormone with low biological into active hormone. The forms with high molecular weight and similar immunological activity may be of another nature. Thus, it has been shown that the biosynthetic nature of a compound such as big big insulin in the rat is doubtful owing to the absence of specific incorporation of labelled leucine into the immunoprecipitate of this fraction. The significance of low molecular weight forms is still little known. There may be breakdown products, biologically active products or biosynthetic products. An example of these forms is supplied by the existence of an alpha sub-unit of gonadotrophin present in the plasma of menopausal women. The interest of analytical methods by radio-receptor, stimulation of cyclase activity in the identification of biological activity of immunoreactive forms, is discussed in relation to immunological forms of enteroglucagon. An unusual aspect of the evolutive and adaptative character of hormonal heterogeneity is given by the gastro-intestinal hormones: secretin, vasoactive intestinal polypeptide and enteroglucagon, have similar structure and mode of action; however, the existence of a specific receptor is a sign of their functional differentiation at molecular level.

Epitopes↗

[Elucidation of the mechanism of fertilization and clinical application of assisted reproductive technology].

Fertilization is the process including many events such as maturation of egg and sperm, attachment, binding, acrosomal reaction, penetration, fusion, cortical reaction, zona reaction and nuclear fusion of both gamete, whereby individual gametes from the female and male unite to create offspring. Although the reason for mechanism of fertilization is still not clearly understood, this process may accelerate the rate adaptation in evolution. In this special lecture, I would like to present our experimental and clinical results especially concerning with morphological, physiological, biochemical and molecular approach on the mechanism of fertilization. 1. Development and maturation of follicles and oocytes. It is well known that pituitary FSH, LH control the ovarian function. Follicular development and ovum maturation are also controlled by both pituitary gonadotropins and local factors such as autocrine and paracrine agents. When hMG is injected during 1-6 day of menstrual cycle, several dominant follicles are developed. If hMG is injected after selection of dominant follicles, only one dominant follicle develop in the ovary. When PMS-treated immature rats were injected with immature or mature follicle fluids, rats injected with mature follicular fluid showed strongly suppress in the ovarian weights and numbers of ovulated follicles. Also mature follicle suppress aromatization from and androstenedione to estradiol. These findings mean that mature follicular fluid contains inhibitory factors. Apoptosis of granulosa cells and follicular steroids are related to fertilization. 2. Intracellular calcium of oocyte. Intracellular calcium concentration is known to start to increase in a periodic manner after fertilization in oocytes of mammalians. In 65% of tested mouse oocytes, fertilization occurred during 4 hours observation after sperm insemination in vitro. An initial long lasting intracellular calcium concentration was observed and followed by periodic manner. This calcium oscillation is inhibited by calcium blockers such as verpamil and nifedipine, but increased by high concentration of extracellular calcium concentration in the medium. Role of increase of intracellular calcium are understood to prevent polysperm and activate metabolism of oocytes. 3. Glucose metabolism of oocytes. Mouse embryo utilizes pyruvate as an essential nutrient until the 8-cell stage, and glucose thereafter. We have devised non-radiometrie and enzymatic microassay method to measure glucose, deoxyglucose, deoxyglucose 6-phosphate incorporated into individual mouse oocytes and preimplantation embryo. In parallel, the activities of several enzymes of glycolytic pathway were also determined. In this study, glucose metabolism is necessary to develop in fertilized ova with changing activity of enzymes. 4. Molecular bases of ovarian fluid. The zona pellucida ZP is involved in a number of events in fertilization, all these fertilization events occur in the oviduct. Oviductal glycoprotein 200-240 KD has been identified from oviductal zona pellucida. Monoclonal antibody of oviductal glycoprotein reacted with ZP of oviductal egg but not with the ovarian egg. Anti-ZPO antibody inhibit to bind sperm to ZP. Sequences in mouse and hamster oviduct specific glycoprotein are estimated, this glycoprotein mRNA was observed in only oviduct by northern blotting method. These molecular gene expression was observed by in situ hybridization in the oviduct of estrous cycle of hamster. 5. Microinsemination of sperm. Microinsemination of sperm into oocyte is widely used in clinical medicine. Sperm penetration assay (hamster test) is useful method to estimate fertilization capacity of sperm. But immotile sperm cannot estimate it. So modified micro sperm penetration assay was established to estimate fertilization capacity of sperm by using micro-manipulator. Subzonal sperm injection (SUZI) and intracytoplasmic sperm injection (ICSI) promotes fertilization and cleavage rate in immotile

Animals↗

The evolution of a kleptoparasitic system under adaptive dynamics.

Kleptoparasitism, the stealing of food items, is a common biological phenomenon which has been modelled mathematically in a series of recent papers. A common assumption, following early work, was that mixed strategy solutions were not possible. In this paper we consider the evolution of mixed strategies under adaptive dynamics and show that such mixed strategies can be stable solutions under certain assumptions. In particular we revisit the recent paper of Broom et al. (Bull math Biol 66, 1645-1658, 2004) which assumed pure solutions only, and reanalyze the model under this new formulation.

Animals↗

Genome organization, natural genetic engineering and adaptive mutation.

Bacterial evolution is considered in the light of molecular discoveries about genome organization, biochemical mechanisms of genetic change, and cellular control networks. Prokaryotic genetic determinants are organized as modular composites of coding sequences and protein-factor binding sites joined together during evolution. Studies of genetic change have revealed the existence of biochemical functions capable of restructuring the bacterial genome at various levels and joining together different sequence elements. These natural genetic engineering systems can be subject to regulation by signal transduction networks conveying information about the extracellular and intracellular environments. Mu-mediated araB-lacZ coding sequence fusions provide one example of adaptive mutation (increased formation of useful mutations under selection) and illustrate how physiological regulation can modulate the activity of a natural genetic engineering system under specific conditions.

Bacteria↗

Effects of compression on language evolution.

For many adaptive complex systems information about the environment is not simply recorded in a look-up table, but is rather encoded in a theory, schema, or model, which compresses information. The grammar of a language can be viewed as such a schema or theory. In a prior study [Teal et al., 1999] we proposed several conjectures about the learning and evolution of language that should follow from these observations: (C1) compression aids in generalization; (C2) compression occurs more easily in a "smooth," as opposed to a "rugged," problem space: and (C3) constraints from compression make it likely that natural languages evolve towards smooth string spaces. This previous work found general, if not complete support for these three conjectures. Here we build on that study to clarify the relationship between Minimum Description Length (MDL) and error in our model and examine evolution of certain languages in more detail. Our results suggest a fourth conjecture: that all else being equal, (C4) more complex languages change more rapidly during evolution.

Algorithms↗