Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Directed evolution”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 181 records · Page 10Linked to original sources
PubMed1976

Controlling protein evolution.

A method is presented for selecting, with a high degree of specificity, mutants for the enzyme alcohol dehydrogenase (ADH) of Saccharomyces cerevisiae having altered kinetics. The method depends on the facts that a) petite yeast strains (those unable to respire aerobically) have an absolute dependence on the presence of cytoplasmic alcohol dehydrogenase, and b) allyl alcohol is readily oxidized by yeast ADH to the highly poisonous product acrolein. If petite yeast are grown in the presence of allyl alcohol surviving mutants show alterations that can be traced to the ADH structural gene. Eight out of nine spontaneous mutant enzymes and five out of five mutants enzymes induced by nitrosoguanidine exhibited a slower electrophoresis mobility than wild type. There may therefore be some correlation between electrophoretic mobility and function. Of three mutant enzymes purified, one of spontaneous origin and two induced by nitrosoguanidine, each showed a different pattern of altered kinetics and a different specific activity. This strongly suggests that, despite the considerable specificity of the selective procedure, there are many ways in which an enzyme can be altered in response to an environmental stimulus. The implications of these results for the study of protein evolution and some directions for future research are briefly discussed.

Alcohol Oxidoreductases↗
PubMed1989

Behavior, archetypes and the irreversibility of evolution.

There is a tendency in modern evolutionary theory to treat organisms as organized by genetic and developmental interactions, in such a way that these play a major role determining the direction of morphological evolution. Alternatively, in this paper behavior is considered as the most fundamental cohesive factor in the morphological evolution of animals. Some phenomena, such as the existence of evolutionary trends, the maintenance of architectural types in certain taxa, and the irreversibility of evolution are discussed in this light.

Adaptation, Physiological↗
PubMed1996

The anti-beta2-glycoprotein I activity in human anti-phospholipid syndrome sera is due to monoreactive low-affinity autoantibodies directed to epitopes located on native beta2-glycoprotein I and preserved during species' evolution.

To characterize the reactivity pattern of Abs directed to beta2-glycoprotein I (anti-beta2GPI) in patients with anti-phospholipid syndrome, we have purified anti-beta2GPI Abs by affinity chromatography using the IgG fractions from sera of five different anti-phospholipid syndrome patients. Affinity-purified anti-beta2GPI were shown to be representative of Abs found in human sera because their activity could be virtually abolished from the IgG preparations after repeated absorptions on immobilized human beta2GPI column. Our results show that affinity-purified anti-beta2GPI: 1) do react with beta2GPI in the absence of any phospholipid, as demonstrated by the lack of phosphorus contaminant in the employed reagents, as well as by their comparable binding activity before and after extensive delipidation procedure; 2) can recognize beta2GPI regardless of its origin from different animal species; 3) are able to bind soluble beta2GPI with a mean Kd value of 4.65 x 10(-6) M (range 3, 4-7, 2 x 10(-6) M); 4) significantly enhance their binding avidity when beta2GPI is linked to a solid support; and 5) appear to be mainly monoreactive autoantibodies. In conclusion, we have shown that human polyclonal anti-beta2GPI are low affinity, mainly monoreactive autoantibodies directed to an epitope located on native beta2GPI, preserved along the species evolution.

Adolescent↗
PubMed1985

Sequence-directed mutagenesis: evidence from a phylogenetic history of human alpha-interferon genes.

We have studied the potential contribution of template-dependent events to genetic variation in mammals by examining the sequence alterations that have occurred in the recent evolution of human interferon genes. Fifteen members of the human alpha-interferon gene family were aligned, and a phylogenetic history was inferred. Many multiple events are inferred to have occurred in the evolution of the interferon genes and for the majority of these local DNA sequences were present that were capable of serving as templates for their occurrence. We conclude that the DNA sequence has the potential to explain many of the inferred spontaneous events and to explain complex alterations to sequences--i.e., the joint occurrence of base substitutions and insertions/deletions. Thus, such a mechanism would often cause multiple sequence changes as a result of a single mutational event and would provide additional genetic variation for evolution. Sequence-directed mutations would depend upon the local DNA sequences and, hence, would not be random at the DNA level.

Base Sequence↗
PubMed1986

Trophic molecules and evolution of the nervous system.

Although recent work has reemphasized the general importance of ontogeny in evolution, underlying developmental molecular mechanisms are largely undefined. What heritable ontogenetic mechanisms result in the evolution of new morphologies and functions? Such questions are particularly difficult in the nervous system, in which each of 10(11) neurons forms approximately equal to 10(4) specific interconnections. I propose that specific heritable, trophic interactions during development, which determine cell survival and pathway size, form a substrate for neural evolution. This model is based on the observation that neurons are vastly overproduced during ontogeny; neurons, their pathways and connections are dependent on target-derived trophic factors for developmental survival; and co-innervating, functionally and anatomically distinct neural populations compete for common trophic factors for survival. Focusing on sympathetic and sensory neurons, which require the target-derived, trophic protein nerve growth factor at different times for developmental survival, and which innervate common targets, different classes of ontogenetic evolutionary mechanisms may be characterized. Evolution may occur from heritable changes in the structure of trophic gene products or altered timing of expression. Molecular mechanisms underlying heterochrony are thereby described. The model is directly applicable to evolution of the brain and is testable in a variety of situations.

Biological Evolution↗
PubMed1986

[Evolution of blood vessels of the heart wall].

In progressive development of the organisms, the cardio-vascular system perfects, its construction is adequate to the level and character of the animal's metabolism. The hypobranchial arteries, forming in the subbranchial area in fishes, make the immediate source for the branching off the coronary arteries. Comparison of the data concerning the places where the cranial coronary arteries take their origin in amphibia, reptiles, birds and mammalia demonstrates that the evolutional process is directed towards transference of the places of their branching off on the ventral aorta, and then on the nearest distance to the heart. Certain data are obtained on evolution of the blood circulation pathways in the myocardium and, particularly, on presence of blood vessels in the spongy myocardium in Elasmobranchii, Chondrosteoideii, as well as in the alligator. The most important of the myocardial blood vessels at all stages of evolution is their connection with the cardiac chambers. At definite stages of phylogenesis, simultaneously with compactization of the myocardium and formation of veins from the intertrabecular spaces, the subepicardial and intramural veins unite into a single venous system, bringing blood to the cardiac cavity. In birds, mammalia and human being, the coronary vessels have reached a high degree of development, having penetrated by their branches into all layers of the cardiac wall, and thus they exclude the dependence of the myocardial blood supply from the blood that is present in the cardiac cavity.

Amphibians↗
PubMed1988

Posthatching changes in levels and molecular forms of acetylcholinesterase in slow and fast muscles of the chicken: effects of denervation and direct electrical stimulation.

The evolution of acetylcholinesterase (AChE) activity and AChE molecular form distribution were studied in slow-tonic anterior latissimus dorsi (ALD) and in fast-twitch posterior latissimus dorsi (PLD) muscles of chickens 2-18 days of age. In ALD as well as in PLD muscles, the AChE-specific activity increased transiently from day 2 to day 4; the activity then decreased more rapidly in PLD muscle. During this period asymmetric AChE forms decreased dramatically in ALD muscle and the globular forms increased. In PLD muscle, the most striking change was the decline in A8 form between days 2 and 18 of development. Denervation performed at day 2 delayed the normal decrease in AChE-specific activity in PLD muscle, whereas little change was observed in ALD muscle. Moreover, A forms in these two muscles were virtually absent 8 days after denervation. Direct electrical stimulation depressed the rise in AChE-specific activity in denervated PLD muscle and prevented the loss of the A forms. Furthermore, the different molecular forms varied according to the stimulus pattern. In ALD muscle, electrical stimulation failed to prevent the effect of denervation. This study emphasizes the differential response of denervated slow and fast muscles to electrical stimulation and stresses the importance of the frequency of stimulation in the regulation of AChE molecular forms in PLD muscle during development.

Acetylcholinesterase↗
PubMed1986

How does a tadpole know when to metamorphose? A theory linking environmental and hormonal cues.

Tadpoles are unusual among free-living amphibians in having an atonic, non-acid secreting, underdeveloped stomach. Morphologically the typical tadpole foregut is most similar to the flaccid, non-acid secreting stomach of adult female of the gastric-brooding frog, Rheobatrachus, during brooding. In Rheobatrachus the brooding condition is induced by prostaglandin E2 secreted from the mouths of brooded larvae. I propose that typical, free-living tadpoles also excrete prostaglandins of the E family in their oral mucus and that these compounds are naturally swallowed with food particles by the tadpoles. According to this hypothesis, when food is abundant larvae swallow a large amount of mucus and, consequently, a lot of hormone, which retards differentiation of the adult, acid secreting, peristaltic stomach. However, when food is less abundant less food and mucus is swallowed. In this situation less prostaglandin passes down the alimentary tract and the gut proceeds to differentiate. If this theory is correct it provides a direct link between an environmental factor--the availability of food--and an endocrinological factor affecting metamorphosis. The theory is consistent with our current understanding of the endocrinology of metamorphosis, as well as the evolution of direct-development in anurans.

Animals↗
PubMed1994

Geographic distribution and evolution of yellow fever viruses based on direct sequencing of genomic cDNA fragments.

We have compared the nucleotide sequence of an envelope protein gene fragment encoding amino acids 291 to 406 of 22 yellow fever (YF) virus strains of diverse geographic and host origins isolated over a 63 year time span. The nucleotide fragment of viral RNA was examined by direct sequencing of a PCR product derived from complementary DNA. Alignment with the prototype Asibi strain sequence showed divergence of 0 to 21.5% corresponding to a maximum of 5.2% divergence in the amino acid sequence. Taking 10% nucleotide divergence as a cut-off point, the 22 YF virus strains fell into three topotypes which corresponded to different geographical areas, namely West Africa, Central-East Africa, and South America. Two subgroups were defined in West Africa, a genotypic group circulating in the sylvatic zone of the western part of Africa, from western Ivory Coast-Mali to Senegal, and a group responsible for large outbreaks from eastern Ivory Coast-Burkina Faso to Cameroon. Strains from Central-East Africa showed a low ratio of transition:transversion of about 1 instead of 8 to 10 for other strains, when their nucleotide sequences were compared with those of other African strains. This may reflect a more distant relationship between the former strains and the others. No change was observed in the highly conserved amino acid domain encompassing the TGD sequence, an important determinant of flavivirus tropism and pathogenesis. Our results support earlier observations on the genetic relationships between YF isolates established by T1 oligonucleotide fingerprinting and offer a useful tool for the understanding of YF virus distribution and evolution.

Amino Acid Sequence↗
PubMed1979

Chromosomal evolution in primates: tentative phylogeny from Microcebus murinus (Prosimian) to man.

The karyotypes of more than 60 species of Primates are studied and compared, with the use of almost all existing banding techniques. There is a very close analogy of chromosome banding between the Simians studied and man. The quantitative or qualitative variations detected all involve the heterochromatin. It is very likely that all the euchromatin (nonvariable R and Q bands) is identical in all the species. Approximately 70% of the bands are common to the Simians and to the Lemurs (Prosimians). In the remaining 30%, technical difficulties prevented a valuable comparison, but this does not exclude the possibility that a complete analogy may exist. Thus, it is very likely that chromosomal evolutions of the Simians, and probably of all the Primates, has occurred without duplication or deficiency of the euchromatin. Approximately 150 rearrangements could be identified and related to the human chromosomes. The types of rearrangement vary from one group (suborder, family, genus) to another. For instance, Robertsonian translocations are preponderant among the Lemuridae (44/57), but are nonexistent among the Pongidae. Chromosome fissions are very frequent amng the Cercopithecidae (10/23), but were not found elsewhere, and pericentric inversions are preponderant in the evolution of Pongidae and man (17/28). This suggest that the chromosomal evolution may be directed by the genic constitution (favouring the occurrence of a particular type of rearrangement, by enzymatic reaction), by the chromosomal morphology (the probability that Robertsonian translocation will be formed depends at least partially on the number of acrocentrics), and by the reproductive behaviour of the animals. Reconstitution of the sequence of the chromosomal rearrangements allowed us to propose a fairly precise genealogy of many Primates, giving the positions of the Catarrhines, the Platyrrhines, and the Prosimians. It was also possible to reconstruct the karyotypes of ancestors that died out several dozen million years ago. The possible role of chromosomal rearrangements in evolution is discussed. It appears necessary to consider different categories of rearrangements separately, depending on their behaviour. The 'nonfavoured' rearrangements, such as pericentric inversions, need to occur in an isolated small population for implanting, by an equivalent of genic derivation. The 'favoured' rearrangements, e.g., Robertsonian translocations, may occur and diffuse in panmictic populations, and accumulate. Their role of gametic barrier could be much more progressive. For discrimination between these two categories, it was necessary to differentiate the selective advantage or disadvantage of the rearrangement itself. It was not possible to show that chromosomal rearrangements play a direct role in modification of the phenotype by position effect. Comparison of the rearrangement that have occurred during evolution and those detected in the human population shows a strong correlation for some of them...

Animals↗
PubMed1994

Recurrent origin of a sexually selected trait in Xiphophorus fishes inferred from a molecular phylogeny.

Darwin believed that sexual selection accounts for the evolution of exaggerated male ornaments, such as the sword-like caudal fin extensions of male fishes of the genus Xiphophorus, that appear detrimental to survival. Swordtails continue to feature prominently in empirical work and theories of sexual selection; the pre-existing bias hypothesis has been offered as an explanation for the evolution of swords in these fishes. Based upon a largely morphological phylogeny, this hypothesis suggests that female preference to mate with sworded males arose in ancestrally swordless species, thus pre-dating the origin of the sword itself and directly driving its evolution. Here we present a molecular phylogeny (based on mitochondrial and nuclear DNA sequences) of Xiphophorus which differs from the traditional one: it indicates that the sword originated and was lost repeatedly. Our phylogeny suggests that the ancestor of the genus is more likely to have possessed a sword than not, thus questioning the applicability of the pre-existing bias hypothesis as an explanation for the evolution of this sexually selected trait.

Animals↗
PubMed1980

Inhibition of photosystem II by formate. Possible evidence for a direct role of bicarbonate in photosynthetic oxygen evolution.

In broken chloroplasts the presence of 100 mM sodium formate at pH 8.2 will specifically lengthen the Photosystem II relaxation times of the reactions S'2 leads to S3 and S'3 leads to S0. Rates of reactions S'0 leads to S1 and S'1 leads to S2 remain unaffected. Evidence is presented which indicates the discrimination among S-states by formate cannot be attributed to a block imposed on the reducing side of Photosystem II. The results are interpreted in context of the known interaction of formate and CO2 which is bound to the Photosystem II reaction center complex. It is proposed that those S-state transitions which show extended relaxation times in the presence of formate must result in the momentary release and rebinding of CO2. Furthermore since formate is acting on the oxygen-evolving side of Photosystem II, it would seem that CO2 is released in reactions that occur there. A chemical model of oxygen evolution is presented. It is based on the hypothesis that hydrated CO2 is the immediate source of photosynthetically evolved oxygen and explains why, under certain conditions formate slows only the S-state transitions S'2 leads to S3 and S'3 leads to S0.

Bicarbonates↗
PubMed1980

Chromosomal interrelationship of hamster species of the genus Mesocricetus.

The similarity of chromosomes and the mode by which differences occurred in the chromosomes of the species comprising the genus Mesocricetus, M. auratus (2n = 44), two "cryptic" species of M. brandti (2n = 44 and 2n = 42) and M. newtoni (2n = 38) were determined. Most of the autosomes and the sex chromosomes have either complete or partial G-band correspondence and thus provide definitive evidence for the taxonomic relationship of these species. The karyotypic differences occurred primarily as a result of deletion of sex chromosome heterochromatin and of autosomal translocations that frequently involved chromosomes with heterochromatic short arms or chromosomes bearing NOR's. Only one Robertsonian centric fusion occurred. Despite the conservatism of arrangement of the genetic material, the chromosomal distribution of heterochromatin diverged during the evolution of these species. M. brandti and newtoni each have a metacentric chromosome with a common long arm matching a submetacentric M. auratus autosome, but a short arm corresponding to two different M. auratus chromosomes. These translocations are crucial for explaining the direction of chromosomal evolution of these species and indicate that M. auratus was the commmon ancestral species and that M. brandti and newtoni subsequently evolved independently.

Animals↗
PubMed1995

[A modern view of the evolution of virulence].

According to the prevailing, traditional view parasites should develop reduced virulence towards their hosts, because more virulent pathogens are more likely to drive the hosts, and thus themselves to extinction. Virulence is considered to be a primitive stage of a parasitive-host association. However the usefulness and validity of this view have been questioned. Recent studies suggest that parasites need not necessarily evolve towards reduced virulence. The points of view of Darwinian medicine in the direction of the evolution of virulence there may be many possible coevolutionary trajectories, depending on the details of the parasite's life-history, the host's behavior and the transmissibility of the parasite. Theoretical and epidemiological evidences indicate that pathogens transmitted by arthropod vectors are significantly more lethal to humans than those transmitted by personal contact. Water borne enteric pathogens are less virulent after purification of water supplies. Recent experiments also support the emerging theory that parasitism can evolve to be either more or less virulent in a long-term host, depending on the way the parasite is transmitted to the host and on the environment in which they live.

Animals↗
PubMed1990

The involucrin genes of pig and dog: comparison of their segments of repeats with those of prosimians and higher primates.

The involucrin genes of the dog and the pig have been cloned and sequenced. Like the corresponding genes of the prosimians, each contains a homologous segment of short tandem repeats at the same position in the coding region. However, the codon sequence of the repeats in the prosimians differs significantly from that of the nonprimate mammals. This evolution has been brought about by a combination of genetic modifications (selective deletions, mutations, and gene conversions). In the anthropoids, this segment of repeats was replaced by a modern one differing in location, sequence, and repeat length. In several of its properties the modern segment has continued the prosimian trend away from the nonprimates. The overall direction of the evolution of this segment has therefore been maintained even though there have been sudden changes in the evolutionary processes acting on the gene.

Animals↗
PubMedDate not supplied

[Experimentation of apiarian preparations for the direct and the indirect capping of the dental pulp].

With a view to extend the range of biologically active preparations for the direct and the indirect capping of the dental pulp the authors have used a paste made from an alcoholic solution of propolis and zincoxyde. The study was carried on in 150 teeth with indirect capping of deep cavities, and 50 teeth with direct capping. The evolution of the cappings was followed clinically, radiologically and morphologically. The results obtained showed that the paste with propolis exerts effects similar to those of zinc eugenate. The morphologic study of the indirect capping showed that secondary dentin developed shortly after the application of the paste, and that it was followed by the development of pulpolites and the sclerous transformation of the pulp. In teeth with direct capping a protective film developed at the opening of the dental chamber. With time the pulpal wound undergoes cicatrization by a process of fibrosis and there is a trend to remineralization. No areas of pulpal degenerescence were found the rest of the pulpal tissue, and this suggests that the paste is more histophilic than the pastes based on calcium hydroxide, with which an area of necrosis occurred at the opening of the chamber, and calcium and fibrous degenerescence occurred in the coronal pulp.

Dental Pulp Capping↗