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Evolution of adaptive neural networks: the role of voltage-dependent K+ channels.

The vestibular pathway of the mollusk Hermissenda crassicornis mediates a reflexive, unconditioned response to disorientation, clinging, that has been conserved during evolution even to the emergence of our own species. This response becomes associated with a visual stimulus (mediated by a precisely ordered visual-vestibular synaptic network) according to principles of Pavlovian conditioning that are also followed in human learning. It is not entirely surprising therefore that molecular and biophysical cascades responsible for this associative learning appear to function in both mollusks and mammals. In brief, combinational elevation of (Ca2+)i, diacylglycerol, and arachidonic acid activates protein kinase C to phosphorylate the Ca2+ and guanosine triphosphate-binding protein, cp20 (now called calexcitin (Nelson T, et al. Proc Natl Acad Sci USA 1996;93:13808-13)), which potently inactivates postsynaptic voltage-dependent K+ currents and thereby increases synaptic weight. Longer term changes included rearrangement of synaptic terminals and modified protein synthesis. This cascade has also been implicated in other associative-learning paradigms (e.g., spatial maze, olfactory discrimination) and as a pathophysiologic target in early Alzheimer's disease. Recent molecular biologic experiments also demonstrate the dependence of associative memory (but not long-term potentiation) on voltage-dependent K+ currents. Theoretic learning models based on these findings focus on dendritic spine clusters and yield computer implementations with powerful pattern-recognition capabilities.

Adaptation, Physiological↗

Adaptive protein evolution at the Adh locus in Drosophila.

Proteins often differ in amino-acid sequence across species. This difference has evolved by the accumulation of neutral mutations by random drift, the fixation of adaptive mutations by selection, or a mixture of the two. Here we propose a simple statistical test of the neutral protein evolution hypothesis based on a comparison of the number of amino-acid replacement substitutions to synonymous substitutions in the coding region of a locus. If the observed substitutions are neutral, the ratio of replacement to synonymous fixed differences between species should be the same as the ratio of replacement to synonymous polymorphisms within species. DNA sequence data on the Adh locus (encoding alcohol dehydrogenase, EC 1.1.1.1) in three species in the Drosophila melanogaster species subgroup do not fit this expectation; instead, there are more fixed replacement differences between species than expected. We suggest that these excess replacement substitutions result from adaptive fixation of selectively advantageous mutations.

Alcohol Dehydrogenase↗

Limits of adaptation: the evolution of selective neutrality.

Many enzymes in intermediary metabolism manifest saturation kinetics in which flux is a concave function of enzyme activity and often of the Michaelis-Menten form. The result is that, when natural selection favors increased enzyme activity so as to maximize flux, a point of diminishing returns will be attained in which any increase in flux results in a disproportionately small increase in fitness. Enzyme activity ultimately will reach a level at which the favorable effect of an increase in activity is of the order 1/(4Ne) or smaller, where Ne is the effective population number. At this point, many mutations that result in small changes in activity will result in negligible changes in fitness and will be selectively nearly neutral. We propose that this process is a mechanism whereby conditions for the occurrence of nearly neutral mutations and gene substitutions can be brought about by the long-continued action of natural selection. Evidence for the hypothesis derives from metabolic theory, direct studies of flux, studies of null and other types of alleles in Drosophila melanogaster and chemostat studies in Escherichia coli. Limitations and complications of the theory include changes in environment or genetic background, enzymes with sharply defined optima of activity, overdominance, pleiotropy, multifunctional enzymes and branched metabolic pathways. We conclude that the theory is a useful synthesis that unites many seemingly unrelated observations. The principal theoretical conclusion is that the conditions for the occurrence of neutral evolution can be brought about as an indirect result of the action of natural selection.

Adaptation, Physiological↗

Temperature as a selective factor in protein evolution: the adaptational strategy of "compromise".

Most of the important functional and structural properties of enzymes are affected by temperature. In order to maintain critical enzymic properties such as regulatory sensitivity, catalytic potential and structural stability, significant changes have been made in enzymes during evolution in different thermal regimes. Regulatory function, as typified by substrate binding ability, has been especially conservative. For a given enzyme, substrate binding ability is maintained at a relatively stable level over the entire temperature range experienced by the organism (enzyme), in spite of wide variation in substrate affinity at temperatures outside the biological range. Similarities in substrate affinity among homologues and analogues of enzymes from bacteria, invertebrates, fishes and mammals, at respective physiological temperatures for the enzymes, demonstrate the crucial importance of regulatory abilities in enzymes. Two facts, (a) that enzymes function at sub-maximal rates, and (b) that low temperature compensation is not effected by wholesale reductions in apparent Km values, argue that regulation outweighs sheer catalytic potential in enzymic function. The efficiency of an enzyme to catalyze a reaction at a rapid rate appears highest in low cell-temperature forms. The finding that catalytic efficiency is inversely correlated with enzymic heat stability suggests that enzymes with relatively great abilities to undergo conformational changes during catalysis are capable of supplying the most energy for activation events, this energy arising in part from the exergonic formation of weak bonds during the activation step in catalysis. Energy changes due to conformational changes may also be used to reduce the net enthalpy change which occurs during ligand binding, a mechanism we refer to as "coupled-compensating enthalpy changes." Comparisons of amino acid compositions of enzyme homologues and analogues from differently thermally adapted species do not reveal major differences, for example, in the overall hydrophobicity of enzymes. We propose that observed differences in enzyme thermal stability derive more from quantitative differences, i.e., differences in total numbers of secondary interactions, than from quilitative differences, i.e., differences in the relative importance of different classes of weak bonds.

Adaptation, Physiological↗

Evolutionary genetics of ruminant lysozymes.

Comparative studies of mammalian lysozymes and their genes have contributed to knowledge of how new functions arise during evolution. The recruitment of lysozymes for functioning in the stomach fluid of ruminants has occurred in response to selection pressures that are partly known and on a time-scale that is known. A semiquantitative analysis of adaptive evolution is thus made possible by the ruminant lysozyme system. Large-scale production of lysozyme by the stomach lining entailed gene duplication as well as a change in gene expression. Remoulding of the lysozyme for working and lasting in the stomach fluid involved accelerated amino acid replacements, which may have been facilitated by intergenic recombination. The possibility that multigene families can accelerate adaptive evolution, by virtue of their capacity for bringing together functionally coupled substitutions, receives emphasis in this review.

Adaptation, Physiological↗

Immune and artificial selection in the haemagglutinin (H) glycoprotein of measles virus.

We present a maximum likelihood (ML) analysis of the selection pressures that have shaped the evolution of the large (L) protein and the haemagglutinin (H) glycoprotein of measles virus (MV). A number of amino acid sites that have potentially been subject to adaptive evolution were identified in the H protein using sequences from every known genotype of MV. All but one of these putative positively selected sites reside within the ectodomain of the H protein, where they often show an association with positions of potential B-cell epitopes and sites known to interact with the CD46 receptor. This suggests that MV may be under pressure from the immune system, albeit relatively weakly, to alter sites within epitopes and hence evade the humoral immune response. The positive selection identified at amino acid 546 was shown to correlate with the passage history of MV isolates in Vero cells. We reveal that Vero cell passaging has the potential to introduce an artificial signal of adaptive evolution through selection for changes that increase affinity for the CD46 receptor.

Amino Acid Sequence↗

Evolution of adaptive immunity.

Antigen receptors and major histocompatibility molecules, key elements required for adaptive immunity, are first seen in jawed fish. So, how did they evolve and have they changed?

Animals↗

Preserved close linkage between the genes encoding troponin I and troponin T, reflecting an evolution of adapter proteins coupling the Ca(2+) signaling of contractility.

Ca(2+)-regulated motility is essential to numerous cellular functions, including muscle contraction. Systems with troponin C, myosin light chain, or calmodulin as the Ca(2+) receptor have evolved in striated muscle and other types of cells to transduce the cytoplasm Ca(2+) signals into allosteric conformational changes of contractile proteins. While these Ca(2+) receptors are homologous proteins, their coupling to the responding elements is quite different in various cell types. The Ca(2+) regulatory system in vertebrate striated muscle represents a highly specialized such signal transduction pathway consisting of the troponin complex and tropomyosin associated with the actin filament. To understand the molecular mechanism in the Ca(2+) regulation of muscle contraction and cell motility, we have revealed a preserved ancestral close linkage between the genes encoding two of the troponin subunits, troponin I and troponin T, in the genome of mouse. The data suggest that the troponin I and troponin T genes may have originated from a single locus and evolved in parallel to encode a striated muscle-specific adapter to couple the Ca(2+) receptor, troponin C, to the actin-myosin contractile machinery. This hypothesis views the three troponin subunits as two structure-function domains: the Ca(2+) receptor and the signal transducing adapter. This model may help to further our understanding of the Ca(2+) regulation of muscle contraction and the structure-function relationship of other potential adapter proteins which are converged to constitute the Ca(2+) signal transduction pathways governing nonmuscle cell motility.

Aging↗

Accuracy and power of the likelihood ratio test in detecting adaptive molecular evolution.

The selective pressure at the protein level is usually measured by the nonsynonymous/synonymous rate ratio (omega = dN/dS), with omega < 1, omega = 1, and omega > 1 indicating purifying (or negative) selection, neutral evolution, and diversifying (or positive) selection, respectively. The omega ratio is commonly calculated as an average over sites. As every functional protein has some amino acid sites under selective constraints, averaging rates across sites leads to low power to detect positive selection. Recently developed models of codon substitution allow the omega ratio to vary among sites and appear to be powerful in detecting positive selection in empirical data analysis. In this study, we used computer simulation to investigate the accuracy and power of the likelihood ratio test (LRT) in detecting positive selection at amino acid sites. The test compares two nested models: one that allows for sites under positive selection (with omega > 1), and another that does not, with the chi2 distribution used for significance testing. We found that use of the chi(2) distribution makes the test conservative, especially when the data contain very short and highly similar sequences. Nevertheless, the LRT is powerful. Although the power can be low with only 5 or 6 sequences in the data, it was nearly 100% in data sets of 17 sequences. Sequence length, sequence divergence, and the strength of positive selection also were found to affect the power of the LRT. The exact distribution assumed for the omega ratio over sites was found not to affect the effectiveness of the LRT.

Adaptation, Biological↗

Positive selection of a gene family during the emergence of humans and African apes.

Gene duplication followed by adaptive evolution is one of the primary forces for the emergence of new gene function. Here we describe the recent proliferation, transposition and selection of a 20-kilobase (kb) duplicated segment throughout 15 Mb of the short arm of human chromosome 16. The dispersal of this segment was accompanied by considerable variation in chromosomal-map location and copy number among hominoid species. In humans, we identified a gene family (morpheus) within the duplicated segment. Comparison of putative protein-encoding exons revealed the most extreme case of positive selection among hominoids. The major episode of enhanced amino-acid replacement occurred after the separation of human and great-ape lineages from the orangutan. Positive selection continued to alter amino-acid composition after the divergence of human and chimpanzee lineages. The rapidity and bias for amino-acid-altering nucleotide changes suggest adaptive evolution of the morpheus gene family during the emergence of humans and African apes. Moreover, some genes emerge and evolve very rapidly, generating copies that bear little similarity to their ancestral precursors. Consequently, a small fraction of human genes may not possess discernible orthologues within the genomes of model organisms.

Animals↗

The probability of fixation in populations of changing size.

The rate of adaptive evolution of a population ultimately depends on the rate of incorporation of beneficial mutations. Even beneficial mutations may, however, be lost from a population since mutant individuals may, by chance, fail to reproduce. In this paper, we calculate the probability of fixation of beneficial mutations that occur in populations of changing size. We examine a number of demographic models, including a population whose size changes once, a population experiencing exponential growth or decline, one that is experiencing logistic growth or decline, and a population that fluctuates in size. The results are based on a branching process model but are shown to be approximate solutions to the diffusion equation describing changes in the probability of fixation over time. Using the diffusion equation, the probability of fixation of deleterious alleles can also be determined for populations that are changing in size. The results developed in this paper can be used to estimate the fixation flux, defined as the rate at which beneficial alleles fix within a population. The fixation flux measures the rate of adaptive evolution of a population and, as we shall see, depends strongly on changes that occur in population size.

Alleles↗

[Quantitative analysis of the teleost brain: evolution and adaptation. 1. A comparative interspecies study].

The intraspecific brain-body weight allometric coefficient, although high in Teleosts (0.49), is different enough from the interspecific one (0.65, almost 2/3) to use only adult specimens for quantitative studies. The low encephalization level of species of great size makes the use of a quadratic curve preferable, although not well adapted to small species. The mean variability of encephalization indices within the species is 8%. Differences of encephalization are noted either between sexes (Misgurnus fossilis) or between ecological milieus (Ictalurus melas). The variability increases progressively from species to genus, family and order; the allometric coefficient grows also, following the general trend for a larger encephalization when the body size is greater. The correlation between the encephalization index and the position within the classification is low; the great number of exceptions makes it necessary to look for other biological and ecological factors, such as the body form, the type of locomotion, the general activity level, the food habits, the way fishes avoid predation and social organization. The index value is due either to the modification of the body size (overweight due to the elongated form of the body, the ballast of poor diets: limivores, coral or sponge eaters, the passive protection against predators of thick scales, spines, etc), or to that of the brain size. In that case, a better encephalization is to be noted in species with a fusiform body, swimming with lateral beats of the caudal peduncle, in active species from mid-waters or pelagic, in predators actively hunting their prey, in species using active ways of protection against predation, in diurnal fishes and in those which have a social way of life needing a good knowledge either of their milieu (territorial behaviour) or of their congeners (social behaviour).

Animals↗

Sequence divergence of measles virus haemagglutinin during natural evolution and adaptation to cell culture.

Phylogenetic analysis of the sequence of the H gene of 75 measles virus (MV) strains (32 published and 43 new sequences) was carried out. The lineage groups described from comparison of the nucleotide sequences encoding the C-terminal regions of the N protein of MV were the same as those derived from the H gene sequences in almost all cases. The databases document a number of distinct genotype switches that have occurred in Madrid (Spain). Well-documented is the complete replacement of lineage group C2, the common European genotype at that time, with that of group D3 around the autumn of 1993. No further isolations of group C2 took place in Madrid after this time. The rate of mutation of the H gene sequences of MV genotype D3 circulating in Madrid from 1993 to 1996 was very low (5 x 10(-4) per annum for a given nucleotide position). This is an order of magnitude lower than the rates of mutation observed in the HN genes of human influenza A viruses. The ratio of expressed over silent mutations indicated that the divergence was not driven by immune selection in this gene. Variations in amino acid 117 of the H protein (F or L) may be related to the ability of some strains to haemagglutinate only in the presence of salt. Adaptation of MV to different primate cell types was associated with very small numbers of mutations in the H gene. The changes could not be predicted when virus previously grown in human B cell lines was adapted to monkey Vero cells. In contrast, rodent brain-adapted viruses displayed a lot of amino acid sequence variation from normal MV strains. There was no convincing evidence for recombination between MV genotypes.

Animals↗