PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Directed evolution”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed1996

Direct development in the lungless salamanders: what are the consequences for developmental biology, evolution and phylogenesis?

Direct development is a widespread alternate reproductive mode in living amphibians that is characterized by evolutionary loss of the free-living, aquatic larval stage. Courtship, mating, and oviposition occur on land, and the terrestrial egg hatches as a fully formed, miniature adult. While it is the most common reproductive mode in urodeles, development outside the reproductive tract of the female that proceeds directly to a terrestrial hatchling occurs in only a single lineage, the lungless salamanders of the family Plethodontidae. Evolution of direct development in plethodontids has contributed importantly to the extraordinary evolutionary success of this speciose, geographically widespread, and morphologically and ecologically diverse taxon. Developmental consequences and correlates include increased egg size and embryonic development time, loss of larval structures and ontogenetic repatterning, and altered pattern formation in organogenesis. Evolutionary and phylogenetic consequences and correlates include the loss of larval constraints and origin of morphological novelty, and frequent homoplasy. Analysis of direct development in an evolutionary context illustrates the complex interplay between processes of phylogenetic divergence and developmental biology, and substantiates the prominent role of developmental processes in both constraining phenotypic variation and promoting phenotypic diversity. Despite the proven suitability of direct-developing plethodontid salamanders for laboratory and field study, knowledge of basic features of their developmental biology remains far below that available for many other urodeles. Examination of such features of these "non-model" organisms is an appropriate and deserving goal of future research.

Animals↗
PubMed1998

Have gene knockouts caused evolutionary reversals in the mammalian first arch?

Many recent gene knockout experiments cause anatomical changes to the jaw region of mice that several investigators claim are evolutionary reversals. Here we evaluate these mutant phenotypes and the assertions of atavism. We argue that following the knockout of Hoxa-2, Dlx-2, MHox, Otx2, and RAR genes, ectopic cartilages arise as secondary consequences of disruptions in normal processes of cell specification, migration, or differentiation. These disruptions cause an excess of mesenchyme to accumulate in a region through which skeletal progenitor cells usually migrate, and at a site of condensation that is normally present in mammals but that is too small to chondrify. We find little evidence that these genes, when disrupted, cause a reversion to any primitive condition and although changes in their expression may have played a role in the evolution of the mammalian jaw, their function during morphogenesis is not sufficiently understood to confirm such hypotheses.

Animals↗
PubMed1999

The effect of high-frequency random mutagenesis on in vitro protein evolution: a study on TEM-1 beta-lactamase.

For a number of years a major limitation in genetic analysis of protein function has been the inability to introduce multiple substitutions at distant sites that would enable the selection of clusters of mutations required for improved or novel biological functions. In order to achieve this, we have recently developed a novel mutagenesis procedure in which the triphosphate derivatives of a pyrimidine (6-(2-deoxy-beta-d-ribofuranosyl)-3, 4-dihydro-8H-pyrimido-[4,5-c][1,2]oxazin-7-one; dP) and a purine (8-oxo-2'-deoxyguanosine; 8-oxodG) nucleoside analogue are employed in DNA synthesis reactions in vitro. The procedure allows control of the mutational load and can yield frequencies of amino acid residue substitutions at least one order of magnitude greater than those previously achieved. Here we report the results of an experiment in which we have hypermutated the bacterial enzyme TEM-1 beta-lactamase and selected small pools (<1.5x10(5)) of clones for enzymatic activity against the beta-lactam antibiotic cefotaxime. The experiment resulted in the isolation of a number of TEM-1 mutants with greatly improved activity against cefotaxime. Among these, clone 3D.5 (E104K:M182T:G238S) exhibited a minimum inhibitory concentration for cefotaxime 20,000-fold higher than wild-type TEM-1 and a catalytic efficiency (kcat/Km) 2383 times higher than the wild-type enzyme. Thus, small pools of hypermutated sequences enabled the selection of one of the most active extended beta-lactamases described so far. These results argue against the accepted view that multiple rounds of low-rate mutagenesis and stepwise selection are essential for in vitro protein evolution and extend the scope of directed molecular evolution to proteins for which no genetic selection is available.

Cefotaxime↗
PubMed1993

Directional selection and the evolution of sex and recombination.

Models of the evolutionary advantages of sex and genetic recombination due to directional selection on a quantitative trait are analysed. The models assume that the trait is controlled by many additive genes. A nor-optimal selection function is used, in which the optimum either moves steadily in one direction, follows an autocorrelated linear Markov process or a random walk, or varies cyclically. The consequences for population mean fitness of a reduction in genetic variance, due to a shift from sexual to asexual reproduction are examined. It is shown that a large reduction in mean fitness can result from such a shift in the case of a steadily moving optimum, under light conditions. The conditions are much more stringent with a cyclical or randomly varying environment, especially if the autocorrelation for a random environment is small. The conditions for spread of a rare modifier affecting the rate of genetic recombination are also examined, and the strength of selection on such a modifier determined. Again, the case of a steadily moving optimum is most favourable for the evolution of increased recombination. The selection pressure on a recombination modifier when a trait is subject to strong truncation selection is calculated, and shown to be large enough to account for observed increases in recombination associated with artificial selection. Theoretical and empirical evidence relevant to evaluating the importance of this model for the evolution of sex and recombination is discussed.

Biological Evolution↗
PubMed1988

Directional mutation pressure and neutral molecular evolution.

A quantitative theory of directional mutation pressure proposed in 1962 explained the wide variation of DNA base composition observed among different bacteria and its small heterogeneity within individual bacterial species. The theory was based on the assumption that the effect of mutation on a genome is not random but has a directionality toward higher or lower guanine-plus-cytosine content of DNA, and this pressure generates directional changes more in neutral parts of the genome than in functionally significant parts. Now that DNA sequence data are available, the theory allows the estimation of the extent of neutrality of directional mutation pressure against selection. Newly defined parameters were used in the analysis, and two apparently universal constants were discovered. Analysis of DNA sequence has revealed that practically all organisms are subject to directional mutation pressure. The theory also offers plausible explanations for the large heterogeneity in guanine-plus-cytosine content among different parts of the vertebrate genome.

Animals↗
PubMedDate not supplied

[Biopolymers and evolution].

Biopolymers are usually studied being extracted from the whole system of a cell or of an organism. Some important features are lost during such a procedure. It is necessary to take into account the behavior of proteins and nucleic acids in metabolic networks and to investigate their evolution. The substitutions of amino-acids metabolic networks residues are biologically possible in the polypeptides and proteins if they do not influence their spatial structure and function. The correlations of the primary structure with these properties are degenerate. The protein can be treated as "an edited statistical copolymer" (Ptitsyn). In the process of "edition" an important role is played by the ions of transient metals. Nucleic acids possess similar properties. It can be shown that the deleterious mutations of proteins can be compensated by the changes of their amount, spatial and temporal characteristics of the synthesis. Not only the structure of the protein is important but also the exact answers of the questions: how much, when and where? The contemporary theory of evolution unites phylogeny and onthogeny. The directionality of evolution is determined both by natural selection and by the already existing structure of an organism. Hence many characters are not adaptive. This is valid also for the molecular level of the structure. Thus three independent groups of facts and suggestions are presented, which confirm the neutral theory of evolution (Kimura) and elucidate its physical meaning. The molecular evolution does not coincide with the biological evolution.

Amino Acid Sequence↗
PubMed1995

Early cranial neural crest migration in the direct-developing frog, Eleutherodactylus coqui.

Direct development is a common reproductive mode in living amphibians characterized by absence of the free-living, aquatic larval stage. In Eleutherodactylus, a species-rich genus of New World frogs, evolution of direct development from the ancestral biphasic ontogeny is correlated with a comprehensive modification in embryonic cranial patterning, including the loss of many larval-specific components and the precocious formation of many adult (postmetamorphic) structures. We use scanning electron microscopy (SEM) to examine the emergence and early migration of cranial neural crest cells in Eleutherodactylus coqui to begin to assess the possible role of the neural crest in mediating these evolutionary changes. As in metamorphosing frogs, cranial crest cells emerge prior to neural fold closure and assemble into three streams: rostral otic, and caudal otic. These streams contribute to the face and first visceral (mandibular) arch, to the second (hyoid) arch, and to posterior (branchial) arches, respectively. Rostrocaudal position, morphology, and/or migration patterns distinguish subpopulations of cells within the rostral stream and caudal otic stream. With the possible exception of the small size of the rostral otic caudal otic streams, evolution of direct development in E. coqui has not altered basic patterns of neural crest emergence or early migration as assessed by SEM. If observed evolutionary changes in embryonic cranial patterning are mediated by the neural crest, then they likely involve later aspects of crest migration or more subtle features related to pattern formation such as cell behavior and commitment, or gene expression.

Animals↗
PubMed1988

Directional selection and the evolution of breeding date in birds.

In many bird species, those pairs that breed earlier in the season have higher reproductive success than those that breed later. Since breeding date is known to be heritable, it is unclear why it does not evolve to an earlier time. Under assumptions outlined by Fisher, a model is developed that shows how breeding date may have considerable additive genetic variance, appear to be under directional selection, and yet not evolve. These results provide a general explanation for a persistent correlation of fitness with a variety of traits in natural populations.

Animals↗
PubMed1976

Evolution of DNA structure: direction, mechanism, rate.

On the basis of the results of an analysis of frequencies of pyrimidine oligonucleotides, the degree of pyrimidine clustering of DNA in species from different taxa has been determined. A tendency for an increase in the index of clustering of DNA was revealed in the sequence: invertebrates, fishes, amphibians, reptiles, birds, mammals. A mechanism is postulated, according to which the increase in the degree of clustering of DNA d-ring the evolution may be associated with the accumulation of mutations, Purine equalibrium Pyrimidine transversions, resulting in a selective enrichment of one of the chains of DNA with pyrimidines and the other- with purines, i.e. in an increase in the degree of purine-pyrimidine imbalance (asymmetry) of DNA complementary chains. This mechanism of DNA evolution is supported by the presence of positive correlation between the degree of clustering and the degree of the chain asymmetry of natural DNAs, as well as the character of the amino acid substitutions in cytochromes c in different species. The progressive evolution of different groups of organisms on the whole may have been accompanied by an acceleration of the rates of evolution of the DNA structure. On the basis of the amino acid sequence of cytochromes c in different species the degree of clustering and the degree of the chain asymmetry of the corresponding structural genes of DNA was found to have a general tendency towards an increase in the following order: invertebrates, fishes, amphibians, reptiles, birds, mammals. Thus, evolution of cytochrome c cistron is a vector process based on a selection of mutations which, on the one hand, are neurtral to protein, and, on the other hand, result in the sense chain of DNA being enriched with pyrimidines and the nonsense one (and the corresponding mRNA)- with purines. Hence, it is the polynucleotide template rather than protein, that must have been the "object of selection". The frequency of substitutions in cytochromes c cistron for vertebrates is 1.56x13(-9) per nucleotide per year. It is believed that the evolutionary modification of the DNA structure may be associated with an increase in the interference resistance of the translation, i.e. with selection for codons of highest readout stability.

Amino Acid Sequence↗
PubMed1991

Prebiotic co-evolution of self-replication and translation or RNA world?

A prebiotic scenario is proposed, based on the recent "domain hypothesis" model (Lahav, 1989, J. molec. Evol. 29, 475-479), suggested for domain propagation of RNA-like molecules in a fluctuating environment. The same system is suggested now not only for the evolution of ribozymes, but also for the evolution of directed peptide synthesis, as follows: Short, self-structured strands (termed prebioectons), each possessing a templatable domain which is chargeable by an amino acid, are the predecessors of tRNA (proto-tRNA). Complementary domains are formed on these prebioectons during an environmental cycle such as wetting-drying, followed by their dissociation from their template domain and ligation, to form the predecessor of mRNA (proto-mRNA). The evolution of directed peptide synthesis is suggested to be based on the ability of the charged prebioectons to attach preferentially to their complementary domains on the proto-mRNA. Two stages of this process are envisioned, namely: (a) Template-directed, random peptide synthesis taking place when non-specifically-charged prebioectons are sequentially attached each to its complementary domain on the proto-mRNA, followed by peptide bond formation. (b) Template-and-sequence-directed peptide synthesis, which can be realized after the "invention" of a catalytic molecule capable of specifically charging a proto-tRNA by an amino acid; this is the crucial evolutionary stage, where a crude genetic code becomes functional. Gradually, catalytic peptides and ribozymes are selected for their functions and evolve, while being encoded in the primitive "memory" of the emerging system. Thus, rather than the RNA monopoly postulated by the RNA World hypothesis, an early co-evolution of primitive enzymes and ribozymes is suggested.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

Isolation and characterization of three mRNAs enriched in embryos of the direct-developing sea urchin Heliocidaris erythrogramma: evolution of larval ectoderm.

The Australian sea urchin Heliocidaris erythro-gramma utilizes a derived direct developmental mode that evolved 8-12 million years ago. From a differential screen we have isolated a small set of cDNAs corresponding to genes more greatly expressed in embryos of H. erythrogramma than in those of its indirect-developing nearest relative, H. tuberculata. The method was biased towards abundant transcripts and did not allow detection of modifications of usage of highly conserved gene family members. Three differentially expressed abundant transcripts were found that potentially encode secreted proteins. Two of these, the arylsulfatase HeARS and the putative lectin HeEL-1, were identifiable as homologues of known proteins. Another gene, HeET-1, may be exclusively expressed in the H. erythrogramma embryo. In situ hybridization experiments demonstrate that all three transcripts are localized to the ectoderm. Two of them, HeET-1 and HeEL-1, are transcribed in an identical domain comprising the larval ectoderm. This region of gene expression has acquired a novel columnar cytology during the evolution of the H. erythrogramma embryo. The third sequence, HeARS, encodes an arylsulfatase homologue. Its expression is uniform in the gastrula, but as the rudiment develops it accumulates to the greatest extent in the invaginating vestibular ectoderm. Through comparisons with indirect-developing species, we show that this concentration of arylsulfatase mRNA in the rudiment is a novel feature of H. erythrogramma development. These data suggest that H. erythrogramma has a unique arrangement of ectodermal gene expression territories. We propose that these reflect larval adaptations that have occurred in the lineage leading to H. erythrogramma, and enabled the evolution of direct development.

Amino Acid Sequence↗
PubMed1976

Evolution of continuous variation: direct approach through joint distribution of genotypes and phenotypes.

The evolutionary dynamics of the joint distribution of genotypes and phenotypes is studied. The model, originally devised to study the joint effects of Mendelian and other types of transmissions, provides results of interest also to the theory of direct Mendelian transmission with natural selection. Assuming bivariate normal distributions, it is shown that in the latter case genotypic and phenotypic means and variances, and genotype-phenotype correlation can be expressed recursively as functions of the parameters for the selection, environmental, and mutation variance. Equilibria and rates of approach for these moments are calculated. It is also proved that in the presence of selection the heritability,defined as the ratio of expected genotypic to expected phenotypic variance after selection, is greater than that before selection by a predictable amount and that it can be greater than unity.

Biological Evolution↗