SEARCH · Search PubMed

Results for “evolvability”

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.

SourceResearch connectionFrom yearThrough year

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

At least 469 records · Page 26Linked to original sources

PubMed1990

Expression in Escherichia coli of the psbO gene encoding the 33 kd protein of the oxygen-evolving complex from spinach.

The cDNA for the 33 kd protein from the oxygen-evolving complex of spinach together with the coding region for the hydrophobic C-terminal part of the transit sequence was cloned into the expression plasmid pDS12/33Ex. The 33 kd protein precursor was expressed in Escherichia coli, secreted into the periplasm and correctly processed to the mature 33 kd protein. Thus the hydrophobic domain of the transit sequence, preceded by a methionine and two lysine residues, can function as a bacterial signal peptide. The periplasmic proteins were released from the cells by osmotic shock and the expressed protein was purified by anion exchange chromatography. The protein was identified by SDS-PAGE and Western blotting. N-terminal sequence analysis showed that the cleavage of the signal peptide occurred at the correct position. The expressed protein could be rebound to CaCl2-washed PSII particles and oxygen evolution was restored in equal amounts by the 33 kd protein from both E. coli and spinach.

Amino Acid Sequence↗

PubMed2006

Unresolved boundaries of evolutionary theory and the question of how inheritance systems evolve: 75 years of debate on the evolution of dominance.

One of the key issues in the evolution of life is the evolution of inheritance systems. In population genetics, the earliest attempt at addressing the latter problem revolved around Fisher's theory on the evolution of dominance. Fisher's hypothesis was that inheritance systems could be modified during the evolutionary process in such a way that wild-type phenotypes could become dominant with respect to mutant phenotypes. This would result in the buffering of a population against the deleterious effects of mutations. The debate that ensued on this topic has been one of the most longstanding in evolutionary theory. At present, the prevalent view is that dominance cannot evolve as a direct result of selection. Furthermore, it has been argued that due to inherent constraints in biochemical systems, the manifestation of dominance is a default expectation and hence evolutionary explanations are not necessary. This has led to the position that the subject is generally resolved and no further debate is necessary. However, there are also several studies indicating that dominance levels can be modified as a result of changes in the genetic background. Furthermore, other studies have indicated that dominance selection is possible in certain circumstances. To a large degree, conclusions from both of the latter types of studies have been ignored. In this article, the history of several intellectual and methodological traditions that have contributed to this debate are traced, including experimental genetics, theoretical population genetics and theoretical biochemistry. In the light of both old and contemporary works on this topic, it is argued that contrary to the prevalent view, the evolution of dominance is not a resolved issue. A re-examination of this issue is essential, given that dominance evolution is likely to be an important stepping stone towards understanding the evolution of inheritance systems.

Animals↗

PubMedDate not supplied

Trimeresurus flavoviridis venom gland phospholipase A2 isozymes genes have evolved via accelerated substitutions.

As a step towards understanding the structure and function of phospholipases A2 (PLA2s), five cDNAs encoding Trimeresurus flavoviridis venom gland PLA2 isozymes have been sequenced. They revealed that the 5' and 3' untranslated regions are much more homologous than the protein-coding regions and that base substitutions have occurred at similar rates for the three positions of codons in the protein-coding regions. Such novel findings are of great interest from the viewpoint of molecular evolution. To gain a further insight into this evolutional phenomenon, we have isolated and sequenced six T. flavoviridis PLA2 isozyme genes. Each gene consisted of four exons and three introns and encoded protein of 138 amino-acid residues, including the signal sequence of 16 amino-acid residues. The introns were much more homologous than the protein-coding regions of exons except for the signal peptide-coding region of the first exon. The absence of apparent functional role in the introns suggested that the protein-coding regions, except for the signal peptide-coding domains, have evolved at greater substitution rates than introns. The fact that the numbers of nucleotide substitutions per non-synonymous site are close to or larger than the numbers of nucleotide substitutions per synonymous site for relevant pairs of genes revealed that Darwinian-type accelerated substitutions have occurred in the protein-coding regions of exons. This is compatible with the presence of PLA2 species with diverse physiological activities in the venom.

Amino Acid Sequence↗

PubMed2001

Biologic basis and evolving role of aromatase inhibitors in the management of invasive carcinoma of the breast.

BACKGROUND AND OBJECTIVES: The most powerful predictor of the response of breast cancers to hormonal therapy is the presence of estrogen receptors in the tumor cells. Estrogen receptors are expressed in approximately 35-55% of all breast tumors but up to 80-90% of tumors from women older than 55 years. METHODS: At this time, tamoxifen remains the first-line hormonal therapy for breast cancer of all stages. However, the aromatase inhibitors are evolving into an important treatment option. Aromatase inhibitors prevent the conversion of precursors (androgens) to estrogens. RESULTS: On the basis of several randomized clinical trials, aromatase inhibitors have become established as the second-line therapy for postmenopausal women with advanced breast cancer progressing during tamoxifen therapy. Furthermore, very recent trials support the use of these agents as first-line therapy in place of tamoxifen. CONCLUSIONS: The roles of the selective aromatase inhibitors in the prevention of breast cancer and in the neoadjuvant and adjuvant treatment of early-stage breast cancer are the focus of several planned and ongoing large-scale clinical trials. These trials will answer some of the many questions that remain regarding optimal hormonal therapy for hormone-dependent breast cancer.

Antineoplastic Agents, Hormonal↗

PubMed2004

Proteomic analysis of the oxygen-evolving complex of photosystem II under biotec stress: Studies on Nicotiana benthamiana infected with tobamoviruses.

We have previously shown that tobamovirus infection induces an inhibition of photosystem II electron transport, disturbing the oxygen-evolving complex (OEC). In the infected plants, the OEC polypeptide pattern was modified when compared to healthy plants, the levels of the PsbP and PsbQ extrinsic proteins being lowered to different extents. In this work we have further investigated by two-dimensional polyacrylamide gel electrophoresis (2-DE) the changes on the OEC protein pattern of thylakoid membranes isolated from Nicotiana benthamiana Domin plants infected with the Spanish strain of pepper mild mottle virus. When the thylakoid membranes from healthy plants were analyzed for the presence of PsbO and PsbP proteins by 2-DE (pI range 4-7) and further immunoassayed by using specific-antisera against these two proteins, it was observed that four polypeptides cross-reacted with each antiserum. These data, along with the N-terminal amino acid sequence determined for the eight polypeptides, indicate that the N. benthamiana PsbO and PsbP proteins correspond to protein families. In the silver-stained 2-DE gels of thylakoid membranes isolated at different days postinoculation from virus-infected plants, it was observed that the content of PsbP polypeptides decreased dramatically with respect to those of PsbO, during the progress of the infection. Interestingly, there was a differential decrease of the different PsbP proteins, indicative of a distinct regulation of their expression.

Arabidopsis Proteins↗

PubMed2003

The evolving experience of illness for Chinese women with breast cancer: a qualitative study.

The study of illness meaning in cancer in western communities has usually focused on causal attributions. We report a phenomenological study of 17 Hong Kong Chinese women with breast cancer, interviewed on completion of initial treatment, and describe how the illness experience and hence, meaning evolves for women in the Hong Kong Chinese culture. Themes arising from the identification and treatment of the disease include the difficulty of living in uncertainty and of maintaining and regaining normalcy in a superstitious society. The initial uncertainty of disease detection and the diagnostic process are characterized by shock and disbelief mingled with fear of death. Treatment choice presents women with difficulties arising from more uncertainty over the pressure to make quick decisions and the dilemma of death or mutilation. Following treatment, re-evaluation, re-prioritizing and positive life-re-evaluation occur. Changes in appearance proved problematic for those women who tried to hide their disease to protect themselves against stigmatization and social exclusion. In many ways, these findings parallel studies on western populations, suggesting that a common disease-medical care process is a predominant influence in shaping breast cancer experience. Implications for care are drawn from these data.

Adaptation, Psychological↗

PubMed1996

Cloning of beta-microseminoprotein of the rat: a rapidly evolving mucosal surface protein.

beta-Microseminoprotein is a small, nonglycosylated protein, rich in disulfide bonds, which is present in the secretions of the airways, the gastrointestinal tract, and the urogenital tract. Its function is unknown. It was originally characterized in the human and it has been difficult to identify the homologous protein in species other than primates. We have purified beta-microseminoprotein from rat prostate and from amino acid sequencing we have been able to clone the protein. The results reinforce conclusions reached earlier that beta-microseminoprotein is a rapidly evolving protein. Overall amino acid identities are only 45, 50, and 40% when the rat protein is compared with the proteins from the human, the ape, and the pig, respectively. However, the 10 cysteines are all completely invariant between these four species. The cloning of beta-microseminoprotein in the rat have substantially improved the possibilities to reveal the function of this mucosal surface protein.

Amino Acid Sequence↗

PubMed2000

A novel cryptic exon in intron 2 of the human dystrophin gene evolved from an intron by acquiring consensus sequences for splicing at different stages of anthropoid evolution.

The dystrophin gene, which is mutated in Duchenne muscular dystrophy, is thus the largest human gene. A full spectrum of splicing of the dystrophin transcript has not been elucidated yet, though more than 10 alternative splicings have been identified in the 5' region of the dystrophin gene. In this study, two novel dystrophin transcripts containing a 140-nucleotide insertion precisely between exons 2 and 8 or between exons 2 and 18 were identified in skeletal muscle. The genomic region corresponding to and surrounding this 140-nucleotide sequence was sequenced to reveal that the insertion possessed a branch point and both acceptor and donor splice site consensus sequences perfectly. Therefore, the 140-bp insertion sequence was considered to be a novel exon. The novel exon was mapped to intron 2 and was designated exon 2a. Reverse-transcription PCR screening for transcripts containing exon 2a in 12 human tissues revealed its presence in 3 of them, including skeletal muscle. Phylogenetic studies disclosed that exon 2a evolved from intron DNA by the progressive acquisition of nucleotide substitutions in ancestral hominoids.

Animals↗

PubMed1995

Microsatellites evolve more rapidly in humans than in chimpanzees.

Microsatellites are highly polymorphic markers consisting of varying numbers of tandem repeats. At different loci, these repeats can consist of one to five nucleotides. Microsatellites have been used in many fields of genetics, including genetic mapping, linkage disequilibrium analyses, forensic studies, and population genetics. It is important that we understand their mutational processes better so that they can be exploited optimally for studies of human diversity and evolutionary genetics. We have analyzed 24 microsatellite loci in chimpanzees, East Anglians, and Sub-Saharan Africans. The stepwise-weighted genetic distances between the humans and the chimpanzees and between the two human populations were calculated according to the method described by Deka et al. (1994, Genomics 22, 226-230). The ratio of the genetic distances between the chimpanzees and the humans relative to that between the Africans and the East Anglians was more than 10 times smaller than expected. This suggests that microsatellites have evolved more rapidly in humans than in chimpanzees.

Animals↗

PubMed1998

The two functional keratin 6 genes of mouse are differentially regulated and evolved independently from their human orthologs.

The type II keratin 6 (K6) features a complex expression pattern, with a constitutive component in a subset of stratified epithelia and an inducible component following injury and other types of acute challenges. Multiple genes encoding highly related K6 isoforms have been described for human and bovine, a unique feature among mammalian keratin genes. Here we report on the cloning and characterization of two functional genes and their cDNAs encoding the K6 isoforms in mouse and two related pseudogenes. A systematic comparison of the mouse and human K6 genes suggests that they evolved independently after these species diverged. The mK6alpha and mK6beta genes are organized in tandem with the same transcriptional orientation in the mouse genome. Similar to the human isoforms, the coding sequences for mK6alpha and mK6beta isoforms show approximately 95% identity. The two mouse K6 genes are differentially regulated at the mRNA level in several stratified epithelia. The mK6alpha isoform mRNA clearly predominates in intact trunk skin of adult mice, where it is restricted to the outer root sheath of hair follicles. Both mRNAs are induced in epidermis and proximal hair follicles as early as 1 h following acute injury or topical application of phorbol esters and subsequently increase to a comparable extent but with different kinetics. These novel findings have important implications for the evolution, regulation, and function of K6 genes in mammalian species.

Amino Acid Sequence↗

PubMed1997

Modelling evolving populations.

A formalism is presented for modelling the evolutionary dynamics of a population of gene sequences. The formalism was originally developed for describing genetic algorithms. In this paper the formalism is elaborated by considering the evolution of an ensemble of populations. This allows the evolution to be modelled more accurately. To illustrate the formalism the problem of a population of gene sequences evolving in a multiplicative fitness landspace is considered. A comparison with simulations is made and shows very good agreement. More complicated problems have already been investigated including sexual recombination and evolution in a multi-valleyed fitness landscape. These results will be briefly reviewed.

Animals↗

PubMed2002

Evolving the division of labour: generalists, specialists and task allocation.

The evolutionary dynamics of specialization, in the context of the division of labour, are investigated. Individuals associate in groups in which benefits are shared and costs borne individually; each individual is either a generalist who can perform all the necessary tasks, a specialist who performs a sub-set of the necessary tasks, or a parasite who contributes nothing to the group. The implications of the model are explored analytically and through both numerical and Monte Carlo methods. These methods demonstrate the evolution of populations towards stable arrangements of specialists and generalists. The fittest populations are those that divide tasks fairly and associate in large, highly specialized groups. Generalists have a distinct advantage in small groups, but the presence of generalists, ironically, lowers group fitness. Parasites are able to invade both specialized and non-specialized populations. A basic model for the continuous division of labour is also presented, demonstrating a tendency for populations to evolve increasingly unfair divisions of labour. This last result implies that an evolutionary ratchet favours disparity between the workload of specialist populations.

Animals↗

PubMed1993

Chloroplast DNA transgresses species boundaries and evolves at variable rates in the California closed-cone pines (Pinus radiata, P. muricata, and P. attenuata).

We studied phylogenetic relationships among populations and species in the California closed-cone pines (Pinus radiata D. Don, P. attenuata Lemm., and P. muricata D. Don) via chloroplast DNA restriction site analysis. Data on genetic polymorphism within and among 19 populations in the three species were collected using 9 to 20 restriction enzymes and 38 to 384 trees. Because only five clades and extremely low intraclade diversity were found, additional phylogenetic data were collected using a single representative per clade and two outgroup species, P. oocarpa Schiede and P. jeffreyi Loud. In total, 25 restriction enzymes were employed and approximately 2.7 kb surveyed (2.3% of genome). The five clades recognized were Monterey pine, knobcone pine, and the southern, intermediate, and northern races of bishop pine. On the basis of bootstrapping, both Wagner and Dollo parsimony analyses strongly separated the northern and intermediate races of bishop pine from the southern race; knobcone pine from Monterey and bishop pines; and the closed-cone pines from the two outgroups. Approximate divergence times were estimated for the lineages leading to knobcone pine and to the intermediate and northern populations of bishop pine. The position of Monterey pine relative to bishop pine within their monophyletic clade was unresolved. Surprisingly, Montery pine and the southern race of bishop pine were much more similar to one another than was the southern race of bishop pine to its conspecific intermediate and northern races. Both the Monterey and southern bishop pine lineages also evolved severalfold more slowly than did the knobcone pine and intermediate-northern bishop pine lineages.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Evolution↗

PubMed2000

Rapidly evolving lineages impede the resolution of phylogenetic relationships among Clitellata (Annelida).

The phylogenetic relationships of the Clitellata were investigated using a data set with published and new complete or partial 18S rRNA and mtCOI gene sequences of 13 and 49 taxa representing 8 and 14 families, respectively. Three different alignments were considered for 18S, and the possible influence of departures from rate constancy among sites was evaluated by analyses using a Gamma model of rate heterogeneity. Maximum-likelihood estimates of the shape parameter alpha of the Gamma distribution were very low, whatever the alignment or the gene considered, suggesting that phylogenetic reconstructions taking into account the rate heterogeneity among sites are likely to be the most reliable. Analyzed separately, the two genes did not resolve the relationships among the Clitellata, but the consensus tree was congruent with the morphology-based relationships. Our data suggest the inclusion of the Euhirudinea, Acanthobdellida, and Branchiobdellida in the Oligochaeta and suggest the Lumbriculidae as the link between both assemblages. Although separate analyses of both genes, as well as different alignments for the 18S rRNA sequences, yielded conflicting results concerning the phylogenetic position of leeches and leech-like worms vis-à-vis the Oligochaeta, subsequent analyses using the Gamma model greatly reduced the observed inconsistencies. Our analyses show that among the Clitellata, the leeches and the leech-like and gutless worms represent significantly faster evolving lineages. It is suggested that the observed higher mutation rates may be explained by the fact that these lineages contain almost exclusively commensal and/or parasitic taxa.

Animals↗

PubMed2000

Resolution of phylogenetic relationships among recently evolved species as a function of amount of DNA sequence: an empirical study based on woodpeckers (Aves: Picidae).

Synonymous substitutions in the 13 mitochondrial encoded protein genes form a large pool of characters that should approach the ideal for phylogenetic analysis of being independently and identically distributed. Pooling sequences from multiple mitochondrial protein-coding genes should result in statistically more powerful estimates of relationships among species that diverged sufficiently recently that most nucleotide substitutions are synonymous. Cytochrome oxidase I (COI) was sequenced for woodpecker species for which cytochrome b (cyt b) sequences were available. A pairing-design test based on the normal distribution indicated that cyt b evolves more rapidly than COI when all nucleotides are compared but their rates are equal for synonymous substitutions. Nearly all of the phylogenetically informative substitutions among woodpeckers are synonymous. Statistical support for relationships, as measured by bootstrap proportions, increased as the number of nucleotides increased from 1047 (cyt b) to 1512 (COI) to 2559 nucleotides (aggregate data set). Pseudo-bootstrap replicates showed the same trend and increasing the amount of sequence beyond the actual length of 2559 nucleotides to 5120 (2x) resulted in stronger bootstrap support, even though the amount of phylogenetic information was the same. However, the amount of sequence required to resolve an internode depends on the length of the internode and its depth in the phylogeny.

Animals↗

PubMed2000

Neuronal death in newborn striatum after hypoxia-ischemia is necrosis and evolves with oxidative stress.

The mechanisms for neurodegeneration after hypoxia-ischemia (HI) in newborns are not understood. We tested the hypothesis that striatal neuron death is necrosis and evolves with oxidative stress and selective organelle damage. Piglets ( approximately 1 week old) were used in a model of hypoxia-asphyxia and survived for 3, 6, 12, or 24 h. Neuronal death was progressive over 3-24 h recovery, with approximately 80% of putaminal neurons dead at 24 h. Striatal DNA was digested randomly at 6-12 h. Ultrastructurally, dying neurons were necrotic. Damage to the Golgi apparatus and rough endoplasmic reticulum occurred at 3-12 h, while most mitochondria appeared intact until 12 h. Mitochondria showed early suppression of activity, then a transient burst of activity at 6 h, followed by mitochondrial failure (determined by cytochrome c oxidase assay). Cytochrome c was depleted at 6 h after HI and thereafter. Damage to lysosomes occurred within 3-6 h. By 3 h recovery, glutathione levels were reduced, and peroxynitrite-mediated oxidative damage to membrane proteins, determined by immunoblots for nitrotyrosine, occurred at 3-12 h. The Golgi apparatus and cytoskeleton were early targets for extensive tyrosine nitration. Striatal neurons also sustained hydroxyl radical damage to DNA and RNA within 6 h after HI. We conclude that early glutathione depletion and oxidative stress between 3 and 6 h reperfusion promote damage to membrane and cytoskeletal proteins, DNA and RNA, as well as damage to most organelles, thereby causing neuronal necrosis in the striatum of newborns after HI.

Animals↗

PubMed1999

HIV-1 evolves into a nonsyncytium-inducing virus upon prolonged culture in vitro.

HIV-1 LAI is a syncytium-inducing (SI) virus with a broad host cell range. We previously isolated a LAI variant that improved replication in the SupT1 T cell line due to mutations within the C1 and C4 constant regions of the Env protein. We now report that this variant exhibits a severely restricted host cell range, as replication in other T cell lines and primary cells was abolished. Several Env-mediated functions were analyzed to provide a mechanistic explanation for this selective adaptation. The change in host cell tropism was not caused by a switch to a SupT1-specific coreceptor. Biosynthesis of the variant Env glycoprotein was not improved in SupT1 cells, and in fact a small defect in intracellular Env processing was observed. SupT1 infection assays did not reveal an improved Env function either, and a dramatic loss of infectivity was measured with other cell types. The Env-mutated HIV-1 reached an approximately fivefold higher level of virus production in SupT1 cells at the peak of infection. Unlike the LAI virus, the variant did not trigger the formation of syncytia. Our combined results suggest that the HIV-1 variant allows the infected host cell to survive longer, thus producing more viral progeny. The intricate virus-cell interaction results in a balance between optimal virus replication and host cell survival, causing a cytopathic SI isolate to evolve toward a nonsyncytium-inducing (NSI) phenotype in cell culture. These findings may help explain the absence of SI variants in the initial phase of HIV-1 infection, and the results dispute the notion that HIV-1 evolution should always go from the NSI to SI phenotype.

Adaptation, Physiological↗

PubMed2002

Silencing of a gene encoding a protein component of the oxygen-evolving complex of photosystem II enhances virus replication in plants.

It has been suggested that, in addition to viral proteins, host proteins are involved in RNA virus replication. In this study the RNA helicase domain of the Tobacco mosaic virus (TMV) replicase proteins was used as bait in the yeast two-hybrid system to identify tobacco proteins with a putative role in TMV replication. Two host proteins were characterized. One protein (designated #3) belongs to a protein family of ATPases associated with various activities (AAA), while the second host protein (designated #13) is the 33K subunit of the oxygen-evolving complex of photosystem II. Using Tobacco rattle virus vectors, genes #3 and #13 were silenced in Nicotiana benthamiana, after which the plants were challenged by TMV infection. Silencing of gene #13 resulted in a 10-fold increase of TMV accumulation, whereas silencing of gene #3 caused a twofold reduction of TMV accumulation. Additionally, silencing of genes #3 and #13 decreased and increased, respectively, the accumulation of two other viruses. Similar to silencing of gene #13, inhibition of photosystem II by application of an herbicide increased TMV accumulation several fold. Infection of N. benthamiana with TMV resulted in a decrease of #13 mRNA levels. Silencing of gene #13 may reflect a novel strategy of TMV to suppress basal host defense mechanisms. The two-hybrid screenings did not identify tobacco proteins involved in helicase domain-induced N-mediated resistance.

Adenosine Triphosphatases↗