SEARCH · PubMed Health

Results for “regulatory 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 199 records · Page 11Linked to original sources

PubMed2004

Phylogenetic profiling of the Arabidopsis thaliana proteome: what proteins distinguish plants from other organisms?

BACKGROUND: The availability of the complete genome sequence of Arabidopsis thaliana together with those of other organisms provides an opportunity to decipher the genetic factors that define plant form and function. To begin this task, we have classified the nuclear protein-coding genes of Arabidopsis thaliana on the basis of their pattern of sequence similarity to organisms across the three domains of life. RESULTS: We identified 3,848 Arabidopsis proteins that are likely to be found solely within the plant lineage. More than half of these plant-specific proteins are of unknown function, emphasizing the general lack of knowledge of processes unique to plants. Plant-specific proteins that are membrane-associated and/or targeted to the mitochondria or chloroplasts are the most poorly characterized. Analyses of microarray data indicate that genes coding for plant-specific proteins, but not evolutionarily conserved proteins, are more likely to be expressed in an organ-specific manner. A large proportion (13%) of plant-specific proteins are transcription factors, whereas other basic cellular processes are under-represented, suggesting that evolution of plant-specific control of gene expression contributed to making plants different from other eukaryotes. CONCLUSIONS: We identified and characterized the Arabidopsis proteins that are most likely to be plant-specific. Our results provide a genome-wide assessment that supports the hypothesis that evolution of higher plant complexity and diversity is related to the evolution of regulatory mechanisms. Because proteins that are unique to the green plant lineage will not be studied in other model systems, they should be attractive priorities for future studies.

Animals↗

PubMed1997

Steroid receptor phylogeny and vertebrate origins.

Vertebrates appear about 500 million years ago in the fossil record. This is only 25-50 million years after the great explosion of multicellular invertebrate body plans in the early Cambrian. On a geological time scale, this interval is a 'blink of an eye', suggesting that the evolution of regulatory genes is likely to be important in the origins of vertebrates. Here we present evidence for a role of steroid receptors in this process based on a phylogenetic analysis suggesting that receptors for androgens, glucocorticoids, mineralocorticoids, and progesterone evolved from an ancestral steroid receptor gene by two successive duplications over a brief time that could have coincided with the origins of vertebrates. Moreover, the duplications of these steroid receptors may be additional evidence for the two duplications on a genome-scale that have been proposed to be important in the evolution of vertebrates. The two successive duplications of steroid receptor genes and their subsequent sequence divergence leading to steroid-specific receptors that regulate growth, development, reproduction and homeostasis in vertebrates may have been one of the events important in vertebrate survival after the Cambrian during global extinctions that occurred about 440 and 370 million years ago.

Animals↗

PubMed1997

On the bifurcation of blood vessels--Wilhelm Roux's doctoral thesis (Jena 1878)--a seminal work for biophysical modelling in developmental biology.

Wilhelm Roux's doctoral thesis described the relationship between the angle and diameter of bifurcating blood vessels. We have re-read this work in the light of biophysics and developmental biology and found two remarkable aspects hidden among a multitude of observations, rules and exceptions to these rules. First, the author identified the major determinants involved in vascular development; genetics, cybernetics, and mechanics; moreover, he knew that he could not deal with the genetic and regulatory aspects, and could hardly treat the mechanical part adequately. Second, he was deeply convinced that the laws of physics determine the design of organisms, and that a necessity for optimality was inherent in development. We combined the analysis of diameter relationships with the requirement for optimality in a stochastic biophysical model, and concluded that a constant wall-stress condition could define a minimum wall-tissue optimum during arterial development. Hence, almost 120 years after Wilhelm Roux's pioneering work, our model indicates one possible way in which physical laws have determined the evolution of regulatory and structural properties in vessel wall development.

Animals↗

PubMed2006

Domain-specific positive selection contributes to the evolution of Arabidopsis leucine-rich repeat receptor-like kinase (LRR RLK) genes.

Leucine-rich repeat receptor-like kinases (LRR RLKs) comprise the largest group within the plant receptor-like kinase (RLK) superfamily, and the Arabidopsis genome alone contains over 200 LRR RLK genes. Although there is clear evidence for diverse roles played by individual LRR RLK genes in Arabidopsis growth and development, the evolutionary mechanism for this functional diversification is currently unclear. In this study, we focused on the LRRII RLK subfamily to investigate the molecular mechanisms that might have led to the functional differentiation of Arabidopsis LRR RLK genes. Phylogenetic analysis of 14 genes in this subfamily revealed three well-supported groups (I, II, and III). RT-PCR analysis did not find many qualitative differences in expression among these 14 genes in various Arabidopsis tissues, suggesting that evolution of regulatory sequences did not play a major role in their functional divergence. We analyzed substitution patterns in the predicted ligand-binding regions of these genes to examine if positive selection has acted to produce novel ligand-binding specificities, using the nonsynonymous/synonymous rate ratio (d (N)/d (S)) as an indicator of selective pressure. Estimates of d (N)/d (S) ratios from multiple methods indicate that nonsynonymous substitutions accumulated during divergence of the three lineages. Positive selection is likely to have occurred along the lineages ancestral to groups II and III. We suggest that positive selection on the ligand-binding sites of LRRII RLKs promoted diversification of ligand-binding specificities and thus contributed to the functional differentiation of Arabidopsis LRRII RLK genes during evolution.

Amino Acid Sequence↗

PubMed2005

Bacterial choices for the consumption of multiple resources for current and future needs.

Microorganisms differ in their effectiveness in uptake and selection of substances that they bring in from the environment. They also differ in how they balance the allocation of nutrients for immediate and for delayed use. Moreover, they may not take up resources as fast as they seemingly could, and they may extrude derivatives of substances just pumped in. A good deal of these apparent choices must reside in the uptake systems and the linkage of these with the cell's intermediate metabolism. An important feature is that a resource may vary in concentration from time to time, nutrient to nutrient, and habitat to habitat. This variation must have been critical to the evolution of regulatory processes. Some possibilities for the combined uptake and consumption are considered for substrates serving the same (homologous) and different (heterologous) roles for the bacterium. From the membrane transport processes diagrammed in Fig. 1c and Fig. 2 and corresponding computer program given in Appendix A, the combined effect of uptake processes and cell growth can be studied. The model can be modified for various alternate models to study the possible control of cellular uptake and metabolism for the range of ecological roles of the bacterium.

Bacteria↗

PubMed1994

Interaction of two LysR-type regulatory proteins CatR and ClcR with heterologous promoters: functional and evolutionary implications.

The soil bacteria Pseudomonas putida can use benzoate or 3-chlorobenzoate as a sole carbon source. Benzoate and 3-chlorobenzoate are converted into catechol and 3-chlorocatechol, respectively, which are in turn converted into tricarboxylic acid cycle intermediates. The catabolic pathways of both compounds proceed through similar intermediates, have similar genetic organization, and have homologous enzymes responsible for different catabolic steps. This has led to suggestions that the plasmid-borne 3-chlorocatechol degradation genes evolved from the chromosomal catechol degradation genes. Both catechol and 3-chlorocatechol pathways are positively regulated by the homologous regulatory proteins CatR and ClcR, respectively. These proteins belong to the LysR family of DNA binding proteins and bind to highly conserved target sequences. We examined the ability of CatR and ClcR to cross-regulate the two pathways. CatR was shown in vitro by DNase I footprinting and gel-shift assays to interact with the clcABD promoter region. Likewise, ClcR was shown to interact in vitro with the catBC promoter region. In in vivo experiments, CatR complemented a ClcR- P. putida strain harboring the clcABD operon for growth on 3-chlorobenzoate. However, ClcR was not capable of complementing a CatR- P. putida strain for growth on benzoate. These observations were confirmed by lacZ-transcriptional fusion expression experiments. Differences in the CatR and ClcR binding sites and their in vitro binding characteristics may explain the ability of CatR and not ClcR to cross-activate. These differences may provide insight about the evolution of regulatory systems in P. putida.

Bacterial Proteins↗

PubMed2007

Compensatory evolution in response to a novel RNA polymerase: orthologous replacement of a central network gene.

A bacteriophage genome was forced to evolve a new system of regulation by replacing its RNA polymerase (RNAP) gene, a central component of the phage developmental pathway, with that of a relative. The experiment used the obligate lytic phage T7 and the RNAP gene of phage T3. T7 RNAP uses 17 phage promoters, which are responsible for all middle and late gene expression, DNA replication, and progeny maturation, but the enzyme has known physical contacts with only 2 other phage proteins. T3 RNAP was supplied in trans by the bacterial host to a T7 genome lacking its own RNAP gene and the phage population was continually propagated on naive bacteria throughout the adaptation. Evolution of the T3 RNAP gene was thereby prevented, and selection was for the evolution of regulatory signals throughout the phage genome. T3 RNAP transcribes from T7 promoters only at low levels, but a single mutation in the promoter confers high expression, providing a ready mechanism for reevolution of gene expression in this system. When selected for rapid growth, fitness of the engineered phage evolved from a low of 5 doublings/h to 33 doublings/h, close to the expected maximum of 37 doublings/h. However, the experiment was terminated before it could be determined accurately that fitness had reached an obvious plateau, and it is not known whether further adaptation could have resulted in complete recovery of fitness. More than 30 mutations were observed in the evolved genome, but changes were found in only 9 of the 16 promoters, and several coding changes occurred in genes with no known contacts with the RNAP. Surprisingly, the T7 genome adapted to T3 RNAP also maintained high fitness when using T7 RNAP, suggesting that the extreme incompatibility of T7 elements with T3 RNAP is not an invariant property of divergence in these expression systems.

Bacteriophage T3↗

PubMed1999

Themes from a NASA workshop on gene regulatory processes in development and evolution.

A memorable workshop, focused on causal mechanisms in metazoan evolution and sponsored by NASA, was held in early June 1998, at MBL. The workshop was organized by Mike Levine and Eric H. Davidson, and it included the PI and associates from 12 different laboratories, a total of about 30 people. Each laboratory had about two and one half hours in which to represent its recent research and cast up its current ideas for an often intense discussion. In the following we have tried to enunciate some of the major themes that emerged, and to reflect on their implications. The opinions voiced are our own. We would like to tender apologies over those contributions we have not been able to include, but this is not, strictly speaking, a meeting review. Rather we have focused on those topics that bear more directly on evolutionary mechanisms, and have therefore slighted some presentations (including some of our own), that were oriented mainly toward developmental processes. J. Exp. Zool. (Mol. Dev. Evol. ) 285:104-115, 1999.

Animals↗

PubMed2006

Diversity of contactin mRNA in human brain tumors.

In order to address the molecular signature of human glioma, we investigated the polymorphism of 5'UTR of the mRNA of Contactin, an adhesion molecule which plays a role in the invasive behavior of these tumors. Contactin mRNA is identified by RT-PCR and a strategy based on rapid amplification of cDNA ends (RACE) reveals different 5'UTRs resulting from both an alternative use of two types of leader exons and a splicing mechanism within the 5'UTR. The spliced exon is an Alu-containing element specific to the primate lineage, thus indicating a recent evolution of regulatory processes specific to the simian line that occurs on this gene. Each 5'UTR exhibits different transcription/translation efficiencies and contains features that allow translation to occur independently of the classic cap-dependent mechanism. These data illustrate the complex regulation of Contactin expression in human brain tumors occurring at both transcriptional and translation levels. The different 5'UTRs are differentially expressed in diverse types of human tumors. Thus, the polymorphism occurring within the non-coding part of the Contactin mRNA reveals new opportunities to explore deregulation that occurs during the oncogenic process.

5' Untranslated Regions↗

PubMed2001

Regulatory potential, phyletic distribution and evolution of ancient, intracellular small-molecule-binding domains.

Central cellular functions such as metabolism, solute transport and signal transduction are regulated, in part, via binding of small molecules by specialized domains. Using sensitive methods for sequence profile analysis and protein structure comparison, we exhaustively surveyed the protein sets from completely sequenced genomes for all occurrences of 21 intracellular small-molecule-binding domains (SMBDs) that are represented in at least two of the three major divisions of life (bacteria, archaea and eukaryotes). These included previously characterized domains such as PAS, GAF, ACT and ferredoxins, as well as three newly predicted SMBDs, namely the 4-vinyl reductase (4VR) domain, the NIFX domain and the 3-histidines (3H) domain. Although there are only a limited number of different superfamilies of these ancient SMBDs, they are present in numerous distinct proteins combined with various enzymatic, transport and signal-transducing domains. Most of the SMBDs show considerable evolutionary mobility and are involved in the generation of many lineage-specific domain architectures. Frequent re-invention of analogous architectures involving functionally related, but not homologous, domains was detected, such as, fusion of different SMBDs to several types of DNA-binding domains to form diverse transcription regulators in prokaryotes and eukaryotes. This is suggestive of similar selective forces affecting the diverse SMBDs and resulting in the formation of multidomain proteins that fit a limited number of functional stereotypes. Using the "guilt by association approach", the identification of SMBDs allowed prediction of functions and mode of regulation for a variety of previously uncharacterized proteins.

Amino Acid Sequence↗

PubMed1996

Untranslated sequence upstream of MarA in the multiple antibiotic resistance locus of Escherichia coli is related to the effector-binding domain of the XylS transcriptional activator.

MarA, the 129-amino-acid (aa) protein which plays a crucial role in the multiple antibiotic resistance (Mar) phenotype in Escherichia coli, shows homology to members of the XylS/AraC family of transcriptional regulators. Although these proteins vary in size from around 100 to 350 aa they all contain a DNA-binding domain with a helix-turn-helix motif. The larger ones, e.g., XylS, AraC, and Rob, contain an additional domain either at their amino- or at their carboxyterminus. This domain is important for effector-binding or dimerization or of unknown function. MarA consists only of the DNA-binding component. Nevertheless, a sequence with a coding potential of 141 aa upstream of its ATG start-codon showed 20.5-26.9% aa identity with the corresponding section within the effector-binding domain of XylS from the TOL plasmid of Pseudomonas putida when translated in the same reading frame as MarA. However, the reading frame was interrupted by 11 translational stops. In another frame, this upstream sequence actually codes for a real protein, MarR, that is completely unrelated to XylS. Implications for the putative evolution of regulatory proteins through translocation of domains followed by adaptation are discussed.

Amino Acid Sequence↗

PubMed2026

Comparative metabolomic and transcriptomic profiling of flavonoid diversity and antioxidant capacity in three Isatis species.

Flavonoids are key bioactive compounds in plants with significant health benefits. This study employs an integrated multi-omics approach to investigate flavonoid diversity and antioxidant capacity across three Isatis species: I. oblongata, I. tinctoria, and I. indigotica. Metabolomic profiling identified 200 flavonoids, with glycosides being the most abundant class. I. tinctoria exhibited the highest total flavonoid content and antioxidant activity, strongly correlated with the accumulation of 53 core differential flavonoid metabolites, most of which were glycosylated derivatives. Transcriptomic analysis revealed coordinated upregulation of phenylpropanoid pathway genes and specific UDP-glycosyltransferases (UGTs) in I. tinctoria, providing a genetic basis for its enhanced glycoside production. The study establishes a clear genotype-metabolite-phenotype linkage, highlighting glycosylation as a key mechanism underlying flavonoid-driven antioxidant superiority in Isatis. Although the current evidence is primarily correlative, the consistent and strong associations across independent transcriptomic, metabolomic, and antioxidant datasets provide a robust foundation for this conclusion. These findings offer new insights into the metabolic evolution and regulatory networks of flavonoids, with implications for breeding and metabolic engineering of high-value medicinal plants.

Flavonoids↗

PubMed1975

Amino acid sequence of two functional sites in yeast glycogen phosphorylase.

The structure of two functional sites in baker's yeast (Saccharomyces cerevisiae) glycogen phosphorylase (EC 2.4 1.1) was determined as part of a study on the evolution of regulatory enzymes. S-Carboxymethylated, MaBH4-reduced 32-P-labeled yeast phosphorylase a was cleaved with CNBr, thermolysin, and pepsin. Peptides labeled with 32-P or carrying the fluorescent pyridoxyl marker were isolated and purified using ion-exchange chromatography and gel filtration. CNBr cleavage yielded a single radioactive phosphopeptide (42 residues long) and one small fluorescent peptide with the unique sequence epsilon-Pxy-Lys-Phe-Val-Met. Thermolysin digestion gave rise to one radioactive octapeptide and two fluorescent peptides, 15 and 2 residues long, respectively. From a combination of substractive Edman degradations and digestion with yeast protease C, the sequence of the 32-P-labeled octapeptide was established. Phosphothreonine was identified as the sole phosphorylated amino acid, giving the following structure for the site involved in the covalent regulation of yeast phosphorylase: Leu-Thr(P) -Gly-Phe-Leu-Pro-Gln-Glu. The two fluorescent thermolytic peptides, together with two additional pyridoxyl peptides isolated after peptic digestion of the enzyme yielded the following sequence around the site binding pyridoxal-5'-P, the cofactor essential for phosphorylase activity: Ile-Ser-Thr-Ala-Gly-Thr-Glu-Ala-Ser-Gly-Thr-Ser-Asn-Met-Lys(P Pxy)-Phe-Val-Met. While the phosphorylated site bears no resemblance to the site of covalent control in vertebrate phosphorylases, the pyridoxal-P binding site in the yeast enayme displays remarkable homologies with its animal counterparts; the finding that 14 out of 18 amino acids are identical strongly suggests that the cofactor must be directly involved in catalysis.

Amino Acid Sequence↗

PubMed2000

The rice R gene family: two distinct subfamilies containing several miniature inverted-repeat transposable elements.

The R and B genes of maize regulate the anthocyanin biosynthetic pathway and constitute a small gene family whose evolution has been shaped by polyploidization and transposable element activity. To compare the evolution of regulatory genes in the distinct but related genomes of rice and maize, we previously isolated two R homologues from rice (Oryza sativa). The Ra1 gene on chromosome 4 can activate the anthocyanin pathway, whereas the Rb gene, of undetermined function, maps to chromosome 1. In this study, rice R genes have been further characterized. First, we found that an Rb cDNA can induce pigmentation in maize suspension cells. Second, another rice R homologue (Ra2) was identified that is more closely related to Ra1 than to Rb. Domesticated rice and its wild relatives harbor multiple Ra-like and Rb-like genes despite the fact that rice is a true diploid with the smallest genome of all the grass species analyzed to date. Finally, several miniature inverted-repeat transposable elements (MITEs) were found in R family members. Their possible role in hastening the divergence of R genes is discussed.

Amino Acid Sequence↗

PubMed1986

On the specificity of DNA-protein interactions.

In this paper we summarize the various factors that must be considered in establishing the operational specificity of the binding of a protein regulator of gene expression to a DNA target site. We consider informational (combinatorial) aspects of binding-site specification, actual recognition mechanisms, and the thermodynamics of target-site selection against a background of competing pseudospecific and non-(sequence)-specific DNA binding sites. The results provide insight into the design, specification, and possibly the evolution of regulatory proteins and their chromosomal binding targets, as well as into practical aspects of the design of regulatory-protein isolation schemes and physicochemical regulatory considerations in vivo.

Binding Sites↗

PubMed1992

At least three promoters direct expression of the mouse glucocorticoid receptor gene.

We have characterized the gene for the mouse glucocorticoid receptor. The gene spans approximately 110 kilobases, and glucocorticoid receptor transcripts are assembled from nine exons. Expression of the gene is controlled by at least three promoters, resulting in glucocorticoid receptor transcripts with different 5' nontranslated exons. One promoter is cell-specific, found to be active only in T lymphocytes. The other two promoters are active to various degrees in all cell lines and tissues so far analyzed and are located in a CpG island. The promoter activities are accompanied by DNase I hypersensitivity sites in chromatin. In contrast to a conservation of exon-intron structure, differences in promoter organization suggest a divergence between the evolution of regulatory and coding regions among members of the steroid receptor super-family.

Animals↗

PubMedDate not supplied

Allelic expression and genetic distance in hybrid macaque monkeys.

Levels of structural genic divergence at 21 loci encoding blood proteins were quantified in six macaque (Macaca) species, using standard techniques of starch-gel electrophoresis. Genetic distances between all pairs of species fall within a narrow range (0.080 less than or equal to D less than or equal to 0.250; D = 0.164) which is near the lower limit of genetic distances typically observed between other congeneric organisms. In an effort to measure levels of regulatory gene differences between these species, we have examined the patterns of allelic expression in their F1, F2, and backcross hybrids. Nine of the 21 loci examined encode allelic forms of the proteins with different electrophoretic mobilities in at least some of the individual parents of the hybrids. In all cases where expected, hybrids express fully both maternal and paternal allelic products, thus providing no strong evidence ofr a breakdown in the regulatory mechanisms responsible for proper expression of these genes. Results are compared to degrees of allelic repression previously observed in other hybrids, and are discussed within the context of current ideas about rates of regulatory gene evolution in mammals.

Alleles↗

PubMed1987

In vitro maintenance of spermatogenesis in Xenopus laevis testis explants cultured in serum-free media.

Spermatogenesis has been maintained for extended periods in Xenopus laevis testis explants cultured in serum-free media supplemented with bovine serum albumin, insulin, transferrin, follicle-stimulating hormone, dihydrotestosterone, testosterone, retinol, ascorbate, and tocopherol. The organization of the testis fragments was maintained for 28 days, and all stages of development were present throughout the culture period. 3H-Thymidine-labeled secondary (Type B) spermatogonia developed in 28 days into spermatids at the acrosomal vesicle stage whereas labeled zygotene spermatocytes became mature spermatids in 28 days. Spermatogonial proliferation also continued in vitro for 28 days. Germ cell differentiation was not dependent upon exogenous testosterone, ascorbate, or tocopherol since 3H-labeled spermatogonia became mature spermatids in testes cultured 35 days in media lacking these supplements. Autoradiography demonstrated that 55% of the luminal sperm present in explants cultured 10 days had differentiated in vitro. Sperm from testes cultured 10-35 days were similar to sperm from freshly dissected testes with regard to motility and fecundity, and eggs fertilized with sperm from explant cultures developed normally into swimming tadpoles. The results demonstrate the feasibility of maintaining vertebrate spermatogenesis in culture and suggest that in vitro analysis of Xenopus spermatogenesis using defined media may provide important insights into the evolution of regulatory mechanisms in spermatogenesis.

Animals↗