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PubMed2006

Life-history evolution under a production constraint.

The recently formulated metabolic theory of ecology has profound implications for the evolution of life histories. Metabolic rate constrains the scaling of production with body mass, so that larger organisms have lower rates of production on a mass-specific basis than smaller ones. Here, we explore the implications of this constraint for life-history evolution. We show that for a range of very simple life histories, Darwinian fitness is equal to birth rate minus death rate. So, natural selection maximizes birth and production rates and minimizes death rates. This implies that decreased body size will generally be favored because it increases production, so long as mortality is unaffected. Alternatively, increased body size will be favored only if it decreases mortality or enhances reproductive success sufficiently to override the preexisting production constraint. Adaptations that may favor evolution of larger size include niche shifts that decrease mortality by escaping predation or that increase fecundity by exploiting new abundant food sources. These principles can be generalized to better understand the intimate relationship between the genetic currency of evolution and the metabolic currency of ecology.

Adaptation, Physiological↗
PubMedDate not supplied

Experimental investigations in prolonged myocardial ischaemia. Note I. Biology of the myocardial fiber after transient myocardial fiber after transient myocardial ischaemia.

The first ten days' evolution of post-ischaemic lesions of the premonitory or angina pectoris syndrome type was experimentally studied by the challenge of a short-term (10 and 15 min) ischaemia, of an adaptation to ischaemia and an adaptation followed by prolonged ischaemia (20 and 35 min). Worthy of note was the persistence of reversible lesions after short-term ischaemia and adaptation, and the progressive evolution towards cytolysis and cicatrization of some pancicellular foci after adaptation followed by prolonged ischaemia. The role of mitochondrial lesions, of lysosomal hydrolases, the inefficiency of renewed circulation, as well as problems of diagnosis are discussed.

Angina Pectoris↗
PubMed2026

Comparative genomics reveals genotype-phenotype concordance and cryptic resistomes in clinical Pseudomonas aeruginosa.

BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is a major pathogen because of its adaptability. It shows rapid evolution of multidrug resistance (MDR). Phenotype-based diagnostics often fail to detect silent resistance determinants and early adaptive changes. This study integrates phenotypic profiling with whole-genome sequencing (WGS) to examine resistance architecture in clinical isolates from eastern India. METHODS: From 1295 culture-positive P. aeruginosa specimens collected at a tertiary care hospital in eastern India. Using predefined criteria, representative MDR and non-MDR isolates were selected, including distinct resistance phenotypes, specimen-source diversity, and hospital and community-acquired settings; multivariate analysis of resistance profiles illustrated phenotypic diversity. Antimicrobial susceptibility assessed using VITEK-2 and Kirby-Bauer disk diffusion, species identity confirmed by 16 S rRNA sequencing, and genomic analysis processed through a reference-guided workflow. Antimicrobial Resistance (AMR) determinants were identified through CARD, and phylogenetic tree constructed from 454 publicly available P. aeruginosa genomes. RESULTS: MDR exhibited greater sequence divergence relative to PA14 (~ 69,000 variants) than the non-MDR isolate (~ 58,700 variants), with > 92% coverage at ≥ 30X depth. Strong genotype-phenotype concordance observed in MDR isolates across five antibiotic classes, associated with β-lactamase variants (PDC-67, OXA-396) and regulatory adaptations (ArmR, cprS). The non-MDR isolate harboured gyrA (T83I) resistance-associated mutations, PDC-1, and OXA-847 without phenotypic expression, indicating silent resistome. Phylogenetically, MDR isolates clustered tightly within the phylogeny, while the non-MDR isolate formed a distinct lineage. CONCLUSION: Observed genomic differences align with adaptation under antimicrobial selection, though confirmation requires larger collections. The non-MDR isolate retained a silent resistome. Findings highlight limitations of phenotype-only diagnostics, support genomic data integration, and emphasize transcriptomics for hidden resistance expression and regulatory dynamics.

Pseudomonas aeruginosa↗
PubMed2001

Evolving responsively: adaptive mutation.

A basic principle of genetics is that the likelihood that a particular mutation occurs is independent of its phenotypic consequences. The concept of adaptive mutation seemed to challenge this principle with the discoveries of mutations stimulated by stress, some of which allow adaptation to the stress. The emerging mechanisms of adaptive genetic change cast evolution, development and heredity into a new perspective, indicating new models for the genetic changes that fuel these processes.

Adaptation, Physiological↗
PubMed2006

Compartmentalization and evolution of feline immunodeficiency virus between the central nervous system and periphery following intracerebroventricular or systemic inoculation.

The emergence of distinct neuropathogenic strains resulting from the adaptation and the unique evolution of human immunodeficiency virus (HIV) in the brain may contribute to the development of HIV-induced neurological diseases. In this study, the authors tracked early changes in virus evolution and compartmentalization between peripheral tissues and the central nervous system (CNS) after intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) inoculation of animals with cell-free feline immunodeficiency virus (FIV). Using the FIV-NCSU1 envelope V3-V4 heteroduplex tracking assay (HTA), the authors observed a rapid compartmentalization of envelope variants between the CNS and periphery. Animals receiving the i.c.v. inoculation showed two peaks of viral RNA in the cerebrospinal fluid (CSF) with very different HTA patterns. Compared to the initial viral peak in CSF, the second peak showed an increased compartmentalization from plasma, reduced viral diversity, and more divergence from the proviral DNA in peripheral blood mononuclear cells (PBMCs) and the choroid plexus. In contrast, changes in plasma over the same time period were small. Different animals harbored different FIV DNA genotypes with varied regional compartmentalization within the brain. These results demonstrated that the virus within the CNS experienced a relatively independent but variable evolution from the periphery. Initial penetration of virus into the CSF facilitated the development of brain-specific reservoirs and viral diversification within the CNS.

Animals↗
PubMed2002

Codon-substitution models for detecting molecular adaptation at individual sites along specific lineages.

The nonsynonymous (amino acid-altering) to synonymous (silent) substitution rate ratio (omega = d(N)/d(S)) provides a measure of natural selection at the protein level, with omega = 1, >1, and <1, indicating neutral evolution, purifying selection, and positive selection, respectively. Previous studies that used this measure to detect positive selection have often taken an approach of pairwise comparison, estimating substitution rates by averaging over all sites in the protein. As most amino acids in a functional protein are under structural and functional constraints and adaptive evolution probably affects only a few sites at a few time points, this approach of averaging rates over sites and over time has little power. Previously, we developed codon-based substitution models that allow the omega ratio to vary either among lineages or among sites. In this paper we extend previous models to allow the omega ratio to vary both among sites and among lineages and implement the new models in the likelihood framework. These models may be useful for identifying positive selection along prespecified lineages that affects only a few sites in the protein. We apply those branch-site models as well as previous branch- and site-specific models to three data sets: the lysozyme genes from primates, the tumor suppressor BRCA1 genes from primates, and the phytochrome (PHY) gene family in angiosperms. Positive selection is detected in the lysozyme and BRCA genes by both the new and the old models. However, only the new models detected positive selection acting on lineages after gene duplication in the PHY gene family. Additional tests on several data sets suggest that the new models may be useful in detecting positive selection after gene duplication in gene family evolution.

Animals↗
PubMed1964

EVOLUTION OF THE IMMUNE RESPONSE. I. THE PHYLOGENETIC DEVELOPMENT OF ADAPTIVE IMMUNOLOGIC RESPONSIVENESS IN VERTEBRATES.

1. The California hagfish, Eptatretus stoutii, seems to be completely lacking in adaptive immunity: it forms no detectable circulating antibody despite intensive stimulation with a range of antigens; it does not show reactivity to old tuberculin following sensitization with BCG; and gives no evidence of homograft immunity. 2. Studies on the sea lamprey, Petromyzon marinus, have been limited to the response to bacteriophage T(2) and hemocyanin in small groups of spawning animals. They suggest that the lamprey may have a low degree of immunologic reactivity. 3. One holostean, the bowfin (Amia calva) and the guitarfish (Rhinobatos productus), an elasmobranch, showed a low level of primary response to phage and hemocyanin. The response is slow and antibody levels low. Both the bowfin and the guitarfish showed a vigorous secondary response to phage, but neither showed much enhancement of reactivity to hemocyanin in the secondary response. The bowfin formed precipitating antibody to hemocyanin, but the guitarfish did not. Both hemagglutinating and precipitating antibody to hemocyanin were also observed in the primary response of the black bass. 4. The bowfin was successfully sensitized to Ascaris antigen, and lesions of the delayed type developed after challenge at varying intervals following sensitization. 5. The horned shark (Heterodontus franciscii) regularly cleared hemocyanin from the circulation after both primary and secondary antigenic stimulation, and regularly formed hemagglutinating antibody, but not precipitating antibody, after both primary and secondary stimulation with this antigen. These animals regularly cleared bacteriophage from the circulation after both the primary and secondary stimulation with bacteriophage T(2). Significant but small amounts of antibody were produced in a few animals in the primary response, and larger amounts in the responding animals after secondary antigenic stimulation. 6. Studies by starch gel and immunoelectrophoresis show that the hagfish has no bands with mobilities of mammalian gamma globulins; that the lamprey has a single, relatively faint band of this type; and that multiple gamma bands are characteristic of the holostean, elasmobranchs, and teleosts studied. By this method of study, the bowfin appeared to have substantial amounts of gamma(2) globulin. 7. We conclude that adaptive immunity and its cellular and humoral correlates developed in the lowest vertebrates, and that a rising level of immunologic reactivity and an increasingly differentiated and complex immunologic mechanism are observed going up the phylogenetic scale from the hagfish, to the lamprey, to the elasmobranchs, to the holosteans, and finally the teleosts.

Adaptation, Physiological↗
PubMed2001

Trade-offs in the evolution of virulence in an indirectly transmitted macroparasite.

The adaptive trade-off theory for the evolution and maintenance of parasite virulence requires that virulence be genetically correlated with other fitness characteristics of the parasite. Many theoretical models rely on a positive correlation between virulence and transmissibility. They assume that high parasite replication rates are associated with a high probability of transmission (and, hence, increased parasite fitness), but also with high levels of damage to the host (high virulence). Schistosomes are macroparasites with an indirect life cycle involving a mammalian and a molluscan host. Here we demonstrate, through the development of five substrains, a genetic basis for schistosome virulence. We used these substrains further in order to investigate the presence of parasite fitness traits that were genetically correlated with virulence. High virulence in the (mouse) definitive host was, as predicted, positively correlated with parasite replication. In contrast, in the (snail) intermediate host high virulence was associated with low parasite replication rates. Variation in infectivity to and parasite replication in the definitive host was suggested as a compensating mechanism for the maintenance of virulence in the snail host. This is the first report of a trade-off in parasite reproductive success across hosts in an indirectly transmitted macroparasite.

Adaptation, Physiological↗
PubMed2003

The evolution of evolvability in genetic linkage patterns.

A number of factors have been proposed that may affect the capacity for an evolutionary system to generate adaptation. One that has received little recent attention among biologists is linkage patterns, or the ordering of genes on chromosomes. In this study, a simple model of genetic interactions, implemented in an evolutionary simulation, demonstrates that clustering of epistatically interacting genes increases the rate of adaptation. Moreover, long-term evolution with inversion can reorganize linkage patterns from random gene ordering into this more modular organization, thereby facilitating adaptation. These results are consistent with a large body of biological observations and some mathematical theory. Although linkage patterns are neutral with respect to individual fitness in this model, they are subject to lineage level selection for evolvability. At least two candidate mechanisms may contribute to improved evolvability under epistatic clustering: clustering may reduce interference between selection on different traits, and it may allow the simultaneous optimization of different recombination rates for gene pairs with additive and epistatic fitness effects.

Adaptation, Physiological↗
PubMed2006

Many genes in fish have species-specific asymmetric rates of molecular evolution.

BACKGROUND: Gene and genome duplication events increase the amount of genetic material that might then contribute to an increase in the genomic and phenotypic complexity of organisms during evolution. Thus, it has been argued that there is a relationship between gene copy number and morphological complexity and/or species diversity. This hypothesis implies that duplicated genes have subdivided or evolved novel functions compared to their pre-duplication proto-orthologs. Such a functional divergence might be caused by an increase in evolutionary rates in one ortholog, by changes in expression, regulatory evolution, insertion of repetitive elements, or due to positive Darwinian selection in one copy. We studied a set of 2466 genes that were present in Danio rerio, Takifugu rubripes, Tetraodon nigroviridis and Oryzias latipes to test (i) for forces of positive Darwinian selection; (ii) how frequently duplicated genes are retained, and (iii) whether novel gene functions might have evolved. RESULTS: 25% (610) of all investigated genes show significantly smaller or higher genetic distances in the genomes of particular fish species compared to their human ortholog than their orthologs in other fish according to relative rate tests. We identified 49 new paralogous pairs of duplicated genes in fish, in which one of the paralogs is under positive Darwinian selection and shows a significantly higher rate of molecular evolution in one of the four fish species, whereas the other copy apparently did not undergo adaptive changes since it retained the original rate of evolution. Among the genes under positive Darwinian selection, we found a surprisingly high number of ATP binding proteins and transcription factors. CONCLUSION: The significant rate difference suggests that the function of these rate-changed genes might be essential for the respective fish species. We demonstrate that the measurement of positive selection is a powerful tool to identify divergence rates of duplicated genes and that this method has the capacity to identify potentially interesting candidates for adaptive gene evolution.

Adenosine Triphosphate↗
PubMed2005

Evolution of the receptor binding phenotype of influenza A (H5) viruses.

Receptor specificity of influenza A/H5 viruses including human 2003-04 isolates was studied. All but two isolates preserved high affinity to Sia2-3Gal (avian-like) receptors. However, two isolates (February, 2003, Hong Kong) demonstrated decreased affinity to Sia2-3Gal and moderate affinity to a Sia2-6Gal (human-like) receptors. These two viruses had a unique Ser227-Asn change in the hemagglutinin molecule. Thus, a single amino acid substitution can significantly alter receptor specificity of avian H5N1 viruses, providing them with an ability to bind to receptors optimal for human influenza viruses. Asian 2003-04 H5 isolates from chickens and humans demonstrated highest affinity to the sulfated trisaccharide Neu5Acalpha2-3Galbeta1-4(6-HSO3)GlcNAcbeta (Su-3'SLN) receptor but, in contrast to 1997 isolates, had increased affinity to fucosylated Su-3'SLN. American poultry H5 viruses also had increased affinity to Su-3'SLN. These data demonstrate that the genetic evolution of avian influenza A(H5N1) viruses is accompanied during adaptation to poultry by the evolution of their receptor specificity.

Amino Acid Sequence↗
PubMed2003

Mating strategies in flowering plants: the outcrossing-selfing paradigm and beyond.

Comparisons of the causes and consequences of cross- and self-fertilization have dominated research on plant mating since Darwin's seminal work on plant reproduction. Here, I provide examples of these accomplishments, but also illustrate new approaches that emphasize the role of floral design and display in pollen dispersal and fitness gain through male function. Wide variation in outcrossing rate characterizes animal-pollinated plants. In species with large floral displays, part of the selfing component of mixed mating can arise from geitonogamy and be maladaptive because of strong inbreeding depression and pollen discounting. Floral strategies that separate the benefits of floral display from the mating costs associated with geitonogamy can resolve these conflicts by reducing lost mating opportunities through male function. The results from experiments with marker genes and floral manipulations provide evidence for the function of herkogamy and dichogamy in reducing self-pollination and promoting pollen dispersal. Evidence is also presented indicating that increased selfing resulting from changes to floral design, or geitonogamy in large clones, can act as a stimulus for the evolution of dioecy. The scope of future research on mating strategies needs to be broadened to include investigations of functional links among flowers, inflorescences and plant architecture within the framework of life-history evolution.

Adaptation, Physiological↗
PubMed2005

A possible new bridge between innate and adaptive immunity: Are the anti-mitochondrial citrate synthase autoantibodies components of the natural antibody network?

Natural antibody (nAb) producing B-1 B cells are considered an intermediate stage of evolution between innate and adaptive immunity. nAbs are immunoglobulins that are produced without antigen priming. nAbs can recognize foreign targets and may serve in the first line of immune defense during an infection. Natural autoantibodies (nAAbs) present in the serum of both healthy humans and patients suffering from systemic autoimmune diseases recognize a set of evolutionarily conserved self-structures. Because of their endosymbiotic evolutionary origin, proteins compartmentalized into mitochondria represent an interesting transition from prokaryotic foreign (non-self) to essential (self) molecules. We investigated the possible overlap in recognized epitopes of innate and self-reactive nAbs and surveyed changes in physiological autoreactivity under pathological autoimmune conditions. Epitope mapping analysis of a mitochondrial inner membrane enzyme, citrate synthase (CS) (EC 2.3.3.1) by synthetic overlapping peptides and phage display libraries using sera from healthy individuals and from patients having systemic autoimmune disease revealed CS recognizing nAAbs with IgM isotype. We analyzed cross reactive epitopes on human CS, bacterial CS, and various standard autoantigens. The anti-CS nAAbs by participating in the nAb network, could function in innate defense mechanisms and at the same time recognize a target antigen (nucleosome) in a systemic autoimmune disease. Thus, at the level of recognized epitopes there is a possible new link between the innate like component and the adaptive-autoimmune arm of the humoral immune system.

Adult↗
PubMed2001

Novel immune-type receptor genes.

Novel immune-type receptor (NITR) genes, which initially were identified in the Southern pufferfish (Spheroides nephelus), encode products which consist of an extracellular variable (V) and V-like C2 (V/C2) domain, a transmembrane region, and a cytoplasmic tail, which typically possesses an immunoreceptor tyrosine-based inhibition motif (ITIM). Multiple NITR genes have been identified in close, contiguous chromosomal linkage. The V regions of NITRs resemble prototypic forms defined for immunoglobulin (Ig) and T-cell antigen receptor (TCR), are present in multiple families and exhibit regionalized variation in sequence, which also occurs in Ig and TCR. Comparisons of exons encoding transmembrane and cytoplasmic regions of multiple NITRs suggest that exon shuffling has factored in the diversification of the NITR gene complex. Zebrafish (Danio rerio) NITRs exhibit many of these characteristics. NITRs that have been identified in additional species of bony fish demonstrate additional variation in the number of extracellular domains as well as in the presence of intramembranous charged residues, cytoplasmic tails and ITIMs. The presence in NITRs of V regions that are related closely to those found in Ig and TCR, as well as regulatory motifs and other structural features that are characteristic of immune inhibitory receptors encoded at the leukocyte receptor cluster, suggests that the NITRs are representative of an integral stage in the evolution of innate and adaptive immune function.

Animals↗