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 145 records · Page 8Linked to original sources
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↗
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↗
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↗
PubMed1987

[Development of spondylodiscopathies in ankylosing spondylitis].

This multicentric study concerns 43 cases of spondylodiscopathies considered, as far as evolution is concerned, according to their radiological aspect. Late erosive forms (33 cases) occur on a rigid spine, sometimes after a trauma (6 cases). The initial radiological sign may be the fracture of a syndesmophyte or of the posterior arch. The evolution of the signs (pinching, erosions, density) is variable: slow or rapid aggravation leading sometimes to an osteosynthesis, extended stabilization over several years, cure by presence of a syndesmophyte or a bony block which, beside an obvious mechanical etiology in most cases, predicts the intervention of an inflammatory factor, isolated or concomitant. Early erosive forms (3 cases) occur in a context of inflammation, on a healthy spine, and sometimes are multifocal and lead rapidly to the formation of bony blocks: they join directly in the evolution of ankylosing spondylarthritis. Pseudo-Pott and pseudo-dystrophic forms (7 cases) present a variable evolution and their interpretation remains debatable.

Adult↗
PubMed2025

Adaptive Evolution for Freshwater Adaptation in Coilia nasus by Directional Selection on Osmoregulation Genes.

The molecular mechanisms underlying the adaptation to freshwater habitats in fish of marine origin remain unclear. Grenadier anchovies, such as Coilia nasus, originate from marine environments and include both anadromous and freshwater-resident conspecifics, making them ideal for studying adaptive evolution from marine to freshwater habitats. We conducted a comparative population genomic and transcriptome analysis of two distinct C. nasus lineages, one anadromous and the other freshwater-resident, collected from mainstream and estuarine regions of the Yangtze River, China. By genome-wide genotyping of the anadromous and the freshwater-resident populations, we observed significant divergence in osmoregulation, energy metabolism, and immune response pathways associated with ecological adaptation and energy expenditure for migration. Some ion transport genes such as CAMK1, ATP1α3, KCNJ1 and SLC30A2 were identified that may contribute to freshwater adaptation. Notably, numerous mineralocorticoid signalling genes (e.g., NR3C2, SGK1, ATP1α3, KCNJ1) exhibit dynamic change between the anadromous and freshwater populations, suggesting an important role for the hormone cortisol in regulating salinity acclimation in euryhaline fish. Among these genes, the ion channel ATP1α3 experienced adaptive amino acid substitutions (Val317Ile and Thr329Ser), which appear to be evolutionary hotspots across migratory species based on ortholog comparisons. These variants may facilitate sodium/potassium transport and highlight salinity tolerance as a key driver of divergence in anadromous fish transitioning to freshwater. These results enhance our understanding of the genetic basis underlying freshwater adaptation for an anadromous fish across osmotic boundaries.

Animals↗
PubMed1985

How many processed pseudogenes are accumulated in a gene family?

A simple kinetic model is developed that describes the accumulation of processed pseudogenes in a functional gene family. Insertion of new pseudogenes occurs at rate v per gene and is countered by spontaneous deletion (at rate delta per DNA segment) of segments containing processed pseudogenes. If there are k functional genes in a gene family, the equilibrium number of processed pseudogenes is k(v/delta), and the percentage of functional genes in the gene family at equilibrium is 1/[1 + (v/delta)]. v/delta values estimated for five gene families ranged from 1.7 to 15. This fairly narrow range suggests that the rates of formation and deletion of processed pseudogenes may be positively correlated for these families. If delta is sufficiently large relative to the per nucleotide mutation rate mu (delta greater than 20 mu), processed pseudogenes will show high homology with each other, even in the absence of gene conversion between pseudogenes. We argue that formation of processed pseudogenes may share common pathways with transposable elements and retroviruses, creating the potential for correlated responses in the evolution of processed pseudogenes due to direct selection for control of transposable elements and/or retroviruses. Finally, we discuss the nature of the selective forces that may act directly or indirectly to influence the evolution of processed pseudogenes.

Animals↗
PubMed1978

Gene dosage compensation and the evolution of sex chromosomes.

Dosage compensation is a mechanism by means of which the activity of X-linked or Z-linked genes is made equal in the two sexes of organisms with an XX compared to XY or ZZ compared to ZW basis of sex determination. In mammals, compensation is achieved by the inactivation of one X chromosome in somatic cells of females. In Drosophila, compensation does not involve inactivation. The two X chromosomes in females as well as the single X in males are regulated, and individual genes are thought to respond independently to the regulatory mechanism. It is proposed that in both groups of organisms the evolution of heteromorphic sex chromosomes was gradual and occurred as the direct result of the evolution of dosage compensation rather than the reverse.

Alleles↗
PubMed2025

Advances in tumor subclone formation and mechanisms of growth and invasion.

Tumor subclones refer to distinct cell populations within the same tumor that possess different genetic characteristics. They play a crucial role in understanding tumor heterogeneity, evolution, and therapeutic resistance. The formation of tumor subclones is driven by several key mechanisms, including the inherent genetic instability of tumor cells, which facilitates the accumulation of novel mutations; selective pressures from the tumor microenvironment and therapeutic interventions, which promote the expansion of certain subclones; and epigenetic modifications, such as DNA methylation and histone modifications, which alter gene expression patterns. Major methodologies for studying tumor subclones include single-cell sequencing, liquid biopsy, and spatial transcriptomics, which provide insights into clonal architecture and dynamic evolution. Beyond their direct involvement in tumor growth and invasion, subclones significantly contribute to tumor heterogeneity, immune evasion, and treatment resistance. Thus, an in-depth investigation of tumor subclones not only aids in guiding personalized precision therapy, overcoming drug resistance, and identifying novel therapeutic targets, but also enhances our ability to predict recurrence and metastasis risks while elucidating the mechanisms underlying tumor heterogeneity. The integration of artificial intelligence, big data analytics, and multi-omics technologies is expected to further advance research in tumor subclones, paving the way for novel strategies in cancer diagnosis and treatment. This review aims to provide a comprehensive overview of tumor subclone formation mechanisms, evolutionary models, analytical methods, and clinical implications, offering insights into precision oncology and future translational research.

Humans↗
PubMed1988

Evolution of hepatocellular carcinoma associated with chronic hepatitis B virus infection in Alaskan Eskimos.

Hepatocellular carcinoma (HCC) associated with chronic hepatitis B virus (HBV) infection in Yupik Eskimos in southwestern Alaska, detected in early stages as a result of screening, appears to be more frequently associated with variants of chronic portal inflammation in the noninvolved liver than with fully developed cirrhosis, otherwise common in HBV-associated HCC from other geographic areas. Of 38 patients diagnosed with HCC since 1969, adequate tissue was available from both the tumor and nontumorous liver in 17. Of the 17 specimens, 14 had chronic portal inflammation and three had advanced cirrhosis; 12 of the 14 were from hepatitis B surface antigen carriers. These 12 cases were studied in detail to examine the features accompanying the development of HCC unobscured by cirrhotic transformation. In the noninvolved parenchyma they included hepatocytic nodules as apparent precursors to HCC and, as markers of phenotypic alterations, dysplastic hepatocytes and hepatitis B surface antigen-laden ground-glass hepatocytes. The latter were observed in eight instances and often accumulated in nodules. Parenchyma within 1 mm of the HCC exhibited increased confluent hyperplasia and frequently conspicuous necroinflammation associated with pericellular and periductular fibrosis, which contributed, in addition to fibrous connections between displaced and heavily inflamed portal tracts, to the capsule that was forming in all cases to varying degrees in the pericarcinomatous region. The HCC was uniformly trabecular and in a few specimens, a continuous transition from hyperplasia and dysplasia near the periphery of the tumor to increasing anaplasia in the center could be made out in addition to pressure effects of the HCC. The pericarcinomatous changes, including hyperplasia progressing to neoplasia and necroinflammation, are also observed in experimental models, particularly the woodchuck HCC induced by a hepadna virus related to HBV. Coordinated morphologic and molecular biologic studies on such animal models and on human HCC detected by screening, as for instance in Eskimos, neither complicated by cirrhosis, should elucidate the direction of the evolution of the HCC and the postulated promoting role of the inflammation.

Adolescent↗
PubMed1990

Concentration of bone elements in osteoporosis.

In aging and in osteoporosis, decreased bone density is associated with decreased bone mass. However, changes in the bone mineral phase remain a matter for investigation. In particular, it is unknown whether bone mineral loss is directly related to reduction in bone mass or associated with changes in the concentration of mineral elements in mineralized bone tissue. In this study, the cortical bone concentration of elements was determined in biopsies of the ilium from 33 subjects (12 controls and 21 individuals with untreated severe osteoporosis). Calcium and phosphorus concentrations were evaluated in cortical and trabecular bone using energy-dispersive x-ray (EDX) microanalysis and inductively coupled plasma optical emission spectrometry (ICPOES). Bone concentrations of Na, K, Mg, Cu, Zn, Fe, Sr, Al, B, and Si were also determined in cortical bone using ICPOES. Additionally, the concentration of F in cortical bone was measured with a specific ion electrode and the concentration of Pb was determined by atomic absorption spectrometry. In mineralized bone tissue there was no significant age-dependent variation in the concentration of Ca, P, or other elements either in controls or in osteoporotic subjects. Moreover, the concentration of elements in bone tissue did not differ in the two groups. These results suggest that the decrease in bone density in osteoporosis is directly related to evolution of the bone mass, without detectable changes in the concentration of elements in bone.

Adult↗
PubMed1981

Estimating genetic correlations from inbred strains.

Genetic correlations measure the extent of pleiotropic effects of polygenes on pairs of characters or the closeness of linkage between sets of loci influencing the traits and held in allelic (gametic) disequilibrium. Their importance for research lies primarily in predicting correlated responses of one trait to selection based on values for another, and secondarily in analyzing the complex organization of biological systems. Genetic correlations appear to limit the rate and set the direction of multivariate evolution. In view of this, efficient methods for estimating genetic correlations may be essential for understanding the role of behavior in adaptation and for predicting behavioral change in evolution. In this paper we present methods for the estimation of genetic correlations from inbred strain comparisons. Estimates from inbred strains are relatively easy to obtain and appear to be valid when compared to those derived from more demanding parent-offspring comparisons and to correlated responses to selection.

Alleles↗
PubMed1990

Molecular cytotaxonomy of primates by chromosomal in situ suppression hybridization.

A new strategy for analyzing chromosomal evolution in primates is presented using chromosomal in situ suppression (CISS) hybridization. Biotin-labeled DNA libraries from flow-sorted human chromosomes are hybridized to chromosome preparations of catarrhines, platyrrhines, and prosimians. By this approach rearrangements of chromosomes that occurred during hominoid evolution are visualized directly at the level of DNA sequences, even in primate species with pronounced chromosomal shuffles.

Animals↗
PubMed1989

Intermediates in membrane fusion and bilayer/nonbilayer phase transitions imaged by time-resolved cryo-transmission electron microscopy.

Bilayer-to-nonbilayer phase transitions in phospholipids occur by means of poorly characterized intermediates. Many have proposed that membrane fusion can also occur by formation of these intermediates. Structures for such intermediates were proposed in a recent theory of these transition mechanisms. Using time-resolved cryo-transmission electron Microscopy (TRC-TEM), we have directly visualized the evolution of inverted phase micro-structure in liposomal aggregates. We have identified one of the proposed intermediates, termed an interlamellar attachment (ILA), which has the structure and dimensions predicted by the theory. We show that ILAs are likely to be the structure corresponding to "lipidic particles" observed by freeze-fracture electron microscopy. ILAs appear to assemble the inverted cubic (III) phase by formation of an ILA lattice, as previously proposed. ILAs are also observed to mediate membrane fusion in the same systems, on the same time scale, and under nearly the same conditions in which membrane fusion was observed by fluorescence methods in earlier studies. These earlier studies indicated a linkage between a membrane fusion mechanism and III phase formation. Our micrographs suggest that the same intermediate structure mediates both of those processes.

Lipid Bilayers↗
PubMed1986

Uric acid-iron ion complexes. A new aspect of the antioxidant functions of uric acid.

In order to survive in an oxygen environment, aerobic organisms have developed numerous mechanisms to protect against oxygen radicals and singlet oxygen. One such mechanism, which appears to have attained particular significance during primate evolution, is the direct scavenging of oxygen radicals, singlet oxygen, oxo-haem oxidants and hydroperoxyl radicals by uric acid. In the present paper we demonstrate that another important 'antioxidant' property of uric acid is the ability to form stable co-ordination complexes with iron ions. Formation of urate-Fe3+ complexes dramatically inhibits Fe3+-catalysed ascorbate oxidation, as well as lipid peroxidation in liposomes and rat liver microsomal fraction. In contrast with antioxidant scavenger reactions, the inhibition of ascorbate oxidation and lipid peroxidation provided by urate's ability to bind iron ions does not involve urate oxidation. Association constants (Ka) for urate-iron ion complexes were determined by fluorescence-quenching techniques. The Ka for a 1:1 urate-Fe3+ complex was found to be 2.4 X 10(5), whereas the Ka for a 1:1 urate-Fe2+ complex was determined to be 1.9 X 10(4). Our experiments also revealed that urate can form a 2:1 complex with Fe3+ with an association constant for the second urate molecule (K'a) of approx. 4.5 X 10(5). From these data we estimate an overall stability constant (Ks approximately equal to Ka X K'a) for urate-Fe3+ complexes of approx. 1.1 X 10(11). Polarographic measurements revealed that (upon binding) urate decreases the reduction potential for the Fe2+/Fe3+ half-reaction from -0.77 V to -0.67 V. Thus urate slightly diminishes the oxidizing potential of Fe3+. The present results provide a mechanistic explanation for our previous report that urate protects ascorbate from oxidation in human blood. The almost saturating concentration of urate normally found in human plasma (up to 0.6 mM) represents 5-10 times the plasma ascorbate concentration, and is orders of magnitude higher than the 'free' iron ion concentration. These considerations point to the physiological significance of our findings.

Animals↗