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PubMed1984

Quantitative genetics and developmental constraints on evolution by selection.

It has often been argued that the principles of random mutation and selection are insufficient to account for macroevolutionary phenomena, such as the origin of morphological novelty and directionality in evolution. A third, epigenetic, principle is said to be required and this principle is thought not to be included in microevolutionary theory. The third principle has most recently been identified as internal selection and/or non-random phenotypic effects of mutation. It is shown that the genetic variance/covariance matrix of quantitative genetic theory measures developmental constraints due to internal selection and non-random mutation. The genetic variance/covariance matrix causes the response to selection to deviate from the optimal rate and direction as specified by the selection gradient, which measures direct selection on the phenotypes. Therefore, microevolutionary theory takes account of developmental constraints on evolution by natural selection through the genetic variance/covariance matrix. Theories for predicting the pattern of genetic variance and covariance from stabilizing selection and the phenotypic effects of mutation are discussed.

Biological Evolution↗
PubMed1985

The evolutionary significance of sexual selection.

A model for the joint evolution of a secondary sexual male trait Z and a female mating preference Y is discussed. Recurrence relations for the moments of (Z, Y) are given under the assumption that the traits are binormally distributed. It is shown that female preference for a male character can lead to an equilibrium distribution of the male trait with non-zero variances. The conditions under which the distribution is stable, are given. Unstable situations, in which a continued exaggeration of the male trait occurs, are described. It is demonstrated that the effect of sexual selection on the evolution of the male trait depends on the intensity of natural selection, i.e. the effect of the sexual selection increases when the intensity of natural selection is reduced. The effect of the female preference on the male trait also increases with increasing availability of males. This provides a link to several ecological conditions which have generally been known to be correlated with the degree of sexual selection. Furthermore, it is demonstrated that perturbations away from the equilibrium may cause rapid evolution of the male character, eventually leading to speciation.

Animals↗
PubMed2002

Modelling the competitive growth of Listeria monocytogenes and Listeria innocua in enrichment broths.

The overgrowth of Listeria innocua in enrichment broths designed for the isolation of Listeria monocytogenes is believed to result from two factors: a selective growth advantage of L. innocua, and/or an inhibitory interspecies interaction. The generation times of 13 isolates of L. innocua and L. monocytogenes were determined in Brain Heart Infusion (BHI) and a variety of enrichment media. No significant differences were found in growth characteristics between either species in the various media, suggesting that the growth advantage of L. innocua in enrichment media was not as significant as previously described. Kinetic analysis of mixed cultures of L. monocytogenes and isolates of L. innocua producing a variety of inhibitory activities demonstrated the possibility of an inhibitory interaction between these two species resulting in the overgrowth of the enrichment culture with L. innocua. Modelling the evolution of the ratio between two populations in an enrichment process was used to analyze the impact of a selective growth advantage in L. innocua in an enrichment process for growth of L. monocytogenes. These findings support the widely held view that an overgrowth of L. innocua in the enrichment process can result from both a selective growth advantage as well as the production of inhibitory compounds. From a practical perspective, these interactions can result in an increase in false negatives.

Antibiosis↗
PubMed1979

The use of amino acid sequence analysis in assessing evolution.

The thirteen year history of assessing evolution by amino acid sequence analysis has made apparent the limitations imposed upon this system by the finite nature of the characters. This finiteness exists on several levels and ultimately expresses itself as parallelism, back mutation and the retention of primitive characters in the sequences of proteins from present day species and the putative ancestral protein chains. Sequence analysis shares these problems with other molecular approaches, but because it is concerned both with the nucleotide substitutions in the genome and with the functional roles of proteins, it has unique advantages. For example, the large fluctuation in the rate of fixation of mutations in a protein's evolution can be detected and used to point out the unreliability of any molecular clock for estimating divergence dates. Moreover, when consideration is given to studies which assign functional significance to specific amino acid sites in a protein, changes in function during the descent of a protein can be appreciated and their significance correlated with organismal evolution.

Amino Acid Sequence↗
PubMed1999

Thermodynamics in the present progressive mode and its role in the context of the origin of life.

The origin and evolution of biological organizations proceeding on Earth are put in a nonequilibrium thermodynamic framework within a cosmological context. The dynamic process responsible for chemical evolution leading to the origin of biological being depends upon consumer-dominating thermodynamics, in which the heat sink is taken to be active in extracting heat energy from a body at a higher temperature. Consumer-dominating thermodynamics follows from the fact that when a small hot body contacts a cold heat sink, it decreases the temperature at the possible fastest rate. The fastest temperature drop, when applied to chemical products being synthesized through the energy supplied from an external heat source, is selective in keeping only those products that can decrease the temperature at the fastest rate among the available alternatives. Synthesis of small organic molecules in the small ice grains in interstellar diffuse clouds irradiated by ultraviolet radiation is a representative case of consumer-dominating thermodynamics, in which diffuse clouds serve as cold heat sinks in the cosmological context. Another case of consumer-dominating thermodynamics predominant on Earth especially in the perspective of the origin and evolution of life is with submarine hydrothermal vents, in which the surrounding cold seawater constantly serves as the cold heat sink.

Biological Evolution↗
PubMed1999

Fitness distributions in evolutionary computation: motivation and examples in the continuous domain.

Evolutionary algorithms are, fundamentally, stochastic search procedures. Each next population is a probabilistic function of the current population. Various controls are available to adjust the probability mass function that is used to sample the space of candidate solutions at each generation. For example, the step size of a single-parent variation operator can be adjusted with a corresponding effect on the probability of finding improved solutions and the expected improvement that will be obtained. Examining these statistics as a function of the step size leads to a 'fitness distribution', a function that trades off the expected improvement at each iteration for the probability of that improvement. This paper analyzes the effects of adjusting the step size of Gaussian and Cauchy mutations, as well as a mutation that is a convolution of these two distributions. The results indicate that fitness distributions can be effective in identifying suitable parameter settings for these operators. Some comments on the utility of extending this protocol toward the general diagnosis of evolutionary algorithms is also offered.

Algorithms↗
PubMed1997

Molecular evolution of the second ancient human mariner transposon, Hsmar2, illustrates patterns of neutral evolution in the human genome lineage.

A consensus sequence for the second ancient mariner identified in the human genome, Hsmar2, was constructed by majority rule from full-length and partial sequences of 44 of the +/-1000 copies in the genome. This 1300 base pair (bp) consensus has 31 bp imperfect terminal repeats (ITRs) and encodes a 351 amino acid (aa) mariner transposase. The sequence of this transposase has allowed classification of Hsmar2 as a basal lineage of the irritans subfamily of mariners, sharing at most 38% aa identity with other members of the subfamily. The individual copies in the human genome are all highly mutated from the consensus, having suffered numerous small and some large insertions and deletions (indels), including many insertions of S and J subfamily Alu elements. The copies differ, on average, from the consensus by 11.6%, have suffered 11.8 indels per kilobase (kb), and only 3.7% of the 30 hypermutable CpG dinucleotide pairs in the consensus remain intact. This level of divergence indicates that the ancestrally active Hsmar2 element represented by the consensus was present in the human genome lineage about 80 million years (Myr) ago. Each copy has apparently evolved since then largely independently of the others, and with little constraint on its transposase coding capacity. This pattern of molecular evolution fits the current model for mariner transposon evolution. These copies provide multiple independent datasets for evaluating the pattern of neutral evolution in the human genome, for example, they confirm that most indels are very short and that deletions are twice as common as insertions.

Amino Acid Sequence↗
PubMed2002

Myopathy and rhabdomyolysis with lipid-lowering drugs.

Drug-induced myopathy and rhabdomyolysis are rare adverse drug reactions (ADR). They have been seen after the introduction of modern lipid-lowering drugs more regularly. The first description after medication with clofibrate dates back to 1968. Apparently, all fibrates can induce myopathy. It usually starts after a few days of medication, or after prolonged use, showing muscle weakness and/or pain. Concomitantly, the enzyme creatininephosphokinase (CPK) is raised dramatically. Muscular necrosis can follow leading secondarily to kidney failure, and eventually to death. For the class of statins, myopathy was more often seen after their introduction, and it became their most feared adverse effect, especially in combination of statins with other drugs (mibefradil, gemfibrozil, cyclosporin). In animal models the evolution of the disease and the mechanism of action may be elucidated. Though strong epidemiological data are lacking, the incidence of myopathy is probably similar for all lipid-lowering drugs and is in the range of 0.1-0.5% with monotherapy, increasing to 0.5-2.5% with combination therapy. Severe cases of rhabdomyolysis are rarer, but may have a significant mortality. The market success of cerivastatin within a short period has led to 100s of myopathies and some dozens of deaths. Though interactions on metabolism and ensuing high plasma levels can partially explain myopathy as intoxication, there are strong indications that other (endocrine, metabolic, genetic) factors might play a role in the pathophysiology. The patient population at risk should better be defined and withheld from myopathy-inducing drugs.

Animals↗
PubMedDate not supplied

Evolution and generalization of a single neurone. III. Primitive, regularized, standard, robust and minimax regressions.

We show that during training the single layer perceptron, one can obtain six conventional statistical regressions: a primitive, regularized, standard, the standard with the pseudo-inversion of the covariance matrix, robust, and minimax (support vector). The complexity of the regression equation increases with an increase in the number of iterations. The generalization accuracy depends on the type of the regression obtained during the training, on the data, learning-set size, and, in certain cases, on the distribution of components of the weight vector. For small intrinsic dimensionality of the data and certain distributions of components of the weight vector the single layer perceptron can be trained even with very short learning sequences. The type of the regression obtained in SLP training should be controlled by the sort of cost function as well as by training parameters (the number of iterations, learning step, etc.). Whitening data transformation prior to training the perceptron is a tool to incorporate a prior information into the prediction rule design, and helps both to diminish the generalization error and the training time.

Biological Evolution↗
PubMed2003

The influence of lipid nanocapsule composition on their size distribution.

A formulation process, based on the inversion phase of an emulsion, was used to prepare lipid nanocapsules. Triglycerides, lecithin, salted water and hydroxy stearate of poly(ethylene glycol) were used in the preparation. The amounts of each that allowed nanocapsules to be formed described a feasibility domain within a ternary diagram. The size distribution of various nanoparticulate carriers has already been shown to influence their applications. An experimental mixture design inside the feasibility domain has been used in order to approximate, through an empirical model, the influence of the quantitative composition of nanocapsules on their size distribution. Reduced cubic polynomial equations successfully modelled the evolution of responses in terms of particle average diameters and coefficients of variation. The results were presented using an analysis of response surface showing a scale of possible particle sizes between 20 and 95 nm and a coefficient of variation between 11 and 40%. Furthermore, this technique showed that the proportion of hydrophilic surfactant had a major influence on the average diameter and the size distribution of the particles decreasing when its proportion increased. On the contrary, the coefficient of variation and the average diameter slightly increase with the proportion of triglycerides. Such a tool offers major advantages to design the formulation of particles as a function of the required size distribution.

Caprylates↗
PubMed1997

Mutation for survival.

Adaptive mutations appear in response to selection. In the best-studied system, the two most controversial issues were resolved this year. The mutations are neither Lamarckian nor a peculiarity of bacterial sex, as had been suggested. They occur genome-wide in a hypermutable subpopulation of stressed cells. Genomic 'hot' and 'cold' regions may explain previous failures to detect similar mutations in other systems and at other sites. Stationary phase specific limitation of mismatch repair has also been discovered.

Adaptation, Biological↗
PubMed2001

The effect of cytidine on the structure and function of an RNA ligase ribozyme.

A cytidine-free ribozyme with RNA ligase activity was obtained by in vitro evolution, starting from a pool of random-sequence RNAs that contained only guanosine, adenosine, and uridine. This ribozyme contains 74 nt and catalyzes formation of a 3',5'-phosphodiester linkage with a catalytic rate of 0.016 min(-1). The RNA adopts a simple secondary structure based on a three-way junction motif, with ligation occurring at the end of a stem region located several nucleotides away from the junction. Cytidine was introduced to the cytidine-free ribozyme in a combinatorial fashion and additional rounds of in vitro evolution were carried out to allow the molecule to adapt to this added component. The resulting cytidine-containing ribozyme formed a 3',5' linkage with a catalytic rate of 0.32 min(-1). The improved rate of the cytidine-containing ribozyme was the result of 12 mutations, including seven added cytidines, that remodeled the internal bulge loops located adjacent to the three-way junction and stabilized the peripheral stem regions.

Base Sequence↗
PubMed1997

Evolution of lipidic structures during model membrane fusion and the relation of this process to cell membrane fusion.

The sequence of events involved in poly(ethylene glycol)-mediated fusion of small unilamellar vesicles (SUVs) has been studied. Fusion events were monitored using light scattering for vesicle aggregation, the fluorescence lifetime of membrane probe lipids (DPHpPC and NBD-PS) for membrane mixing, the aqueous fluorescent marker (Tb3+/DPA and H+/HPTS) for contents mixing; and quasi-elastic light scattering for the change in the size of vesicles. Poly(ethylene glycol) is a highly hydrated polymer that can bring vesicle membranes to near molecular contact but is unable to induce vesicle fusion without manipulations that reduce packing density and encourage molecular motions in the backbone regions of both contacting membrane leaflets. Once this condition is achieved, the sequence of events involved in vesicle fusion is shown here to be (1) outer leaflet mixing accompanied by (2) transient pore formation, both occurring on a time scale of approximately 10 s and leading to an initial, reversible intermediate; (3) a 1-3 min delay leading to formation of a fusion-committed second intermediate; (4) inner leaflet mixing on a time scale of ca. 150 s; and (5) contents mixing on a time scale of 150-300 s. Inner leaflet mixing, which has never before been shown to be distinct from outer leaflet mixing, begins simultaneously with, but is completed before, contents mixing. Fusion products, which seem to be large vesicles, are estimated to be formed from four to six SUVs. The fusion intermediates are shown to have merged outer leaflets and distinct inner leaflets prior to formation of fusion pores. Using quasi-elastic light scattering, the initial intermediate was shown to revert to SUVs upon removal of PEG, while the second intermediate irreversibly continued to a fusion pore in the presence or absence of PEG. The sequence of events for this pure lipid bilayer fusion process shows remarkable homology to what is known about the sequence of protein-mediated cell membrane fusion events, suggesting a commonality between these two processes.

Biopolymers↗
PubMed2005

Gas-phase stability of tetrahedral multiply charged anions: a conceptual and computational DFT study.

Multiply charged anions (MCA's) are unstable relative to electron autoejection; however, the repulsive Coulomb barrier (RCB) provides electronic stability. In view of their interest in biological systems, the behavior of isolated AsO(4)(3-), PO(4)(3-), SO(4)(2-), and SeO(4)(2-) in the gas phase and in solution has been studied. To calculate the RCB values, the electrostatic and point charge model-two methods currently used in the literature-are applied, together with a recently introduced Conceptual Density Functional Theory (DFT) based approach. The relative stability of the above-mentioned MCA's is compared. The trends of the RCB are analyzed by including analogous compounds from the second and third row and by passing from dianionic to trianionic systems. Considering the effect of solvent, using the SCI-PCM solvent model, the evolution of the RCB when passing to higher dielectric constants is evaluated. The RCB is related to the properties of the system as polarizability/softness. Both a numerical and a conceptual correlation between the RCB and the global softness is found.

Anions↗
PubMed1999

Directed molecular evolution.

We propose the existence of a relationship of stereochemical complementarity between gene sequences that code for interacting components: nucleic acid-nucleic acid, protein-protein and protein-nucleic acid. Such a relationship would impose evolutionary constraints on the DNA sequences themselves, thus retaining these sequences and governing the direction of the evolutionary process. Therefore, we propose that prebiotic, template-directed autocatalytic synthesis of mutally cognate peptides and polynucleotides resulted in their amplification and evolutionary conservation in contemporary prokaryotic and eukaryotic organisms as a genetic regulatory apparatus. If this proposal is correct, then the relationships between the sequences in DNA coding for these interactions constitute a life code of which the genetic code is only one aspect of the many related interactions encoded in DNA.

Base Sequence↗
PubMed1997

The glycophorin A gene family in gorillas: structure, expression, and comparison with the human and chimpanzee homologues.

Homologues of MN blood group antigens, encoded by members of the glycophorin A (GPA) gene family, are expressed in man, anthropoid apes, and some species of Old World monkeys. Previous studies had shown that a three-gene framework, most closely related to that in man, is present in the chimpanzee. Here we report the genomic structure, transcript map, and protein expression of the GYPA locus in gorillas. Compared to the corresponding human and chimpanzee homologues, gorilla GPA, GPB, and GPB/E genes each showed a high degree of sequence identity, with the same exon-intron organization. However, the expression of exons III, IV or V encoding the extracellular or membrane domains of homologous glycophorins varied among the three species. Gorilla GPA and GPB/E genes were unique in that the former occurred in two allelic forms with or without the expression of exon III, whereas the latter contained one (psi exon III) instead of two silenced exons (psi exons III and IV). Differences from human but not chimpanzee GPA also included the presence of a hybrid M/N epitope and the absence of the sequon for N-glycosylation. Owing to the retention of a functional exon III, gorilla GPB was more similar to chimpanzee GPB than human GPB. A transspecies allele was identified in the gorilla that gave rise to the Henshaw (He)-like antigen similar to that found in man. These results provide further insight into the model for evolution of the GPA gene family, indicating that the mechanisms underlying inter- and intraspecific polymorphism of glycophorins could predate the divergence of gorillas as the consequence of gene duplication and diversification.

Amino Acid Sequence↗