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Results for “regulatory evolution”

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At least 217 records · Page 12Linked to original sources

PubMed2006

Angiogenesis in atherosclerosis: gathering evidence beyond speculation.

PURPOSE OF REVIEW: The present review summarizes evidence for several functions of neovascularization in plaque growth that sustain perfusion beyond limits of diffusion from the artery lumen and outer adventitial vasa vasorum, deposit proatherogenic plasma molecules, recruit immune cells and progenitors, and promote intraplaque hemorrhage. Recent approvals of antiangiogenesis drugs for clinical use in cancer and macular degeneration improve the feasibility of testing whether such agents inhibit plaque angiogenesis and incidental atherosclerosis. RECENT FINDINGS: Improvements in large and small animal models of atherosclerosis and knowledge of the molecular regulation of angiogenesis in development and disease have advanced understanding of plaque angiogenesis. Genetic modifications of angiogenesis molecules in mouse strains susceptible to atherosclerosis provide experimental means to identify native molecules that regulate plaque angiogenesis. Studies of plaque angiogenesis are aided by micro-computed tomography techniques that image vasa vasorum anatomy in relation to the atheroma. SUMMARY: Greater knowledge of plaque angiogenesis regulation is needed to design treatments that target the most critical regulatory pathways. Evolutions in angiogenesis inhibitor treatments for cancer and other diseases call for a need to understand the distinct cardiovascular profiles of different agents to rationally combine agents for optimal selectivity and efficacy in the intended vascular bed.

Angiogenesis Inhibitors↗

PubMed2006

Rhomboid proteins: conserved membrane proteases with divergent biological functions.

The rhomboid gene was discovered in Drosophila, where it encodes a seven transmembrane protein that is the signal-generating component of epidermal growth factor (EGF) receptor signaling during development. Although metazoan developmental regulators are rarely conserved outside the animal kingdom, rhomboid proteins are conserved in all kingdoms of life, but the significance of this remains unclear. Recent biochemical reconstitution and high-resolution crystal structures have provided proof that rhomboid proteins function as novel intramembrane proteases, with a serine protease-like catalytic apparatus embedded within the membrane bilayer, buried in a hydrophilic cavity formed by a protein ring. A thorough consideration of all known examples of rhomboid function suggests that, despite biochemical similarity in mechanism and specificity, rhomboid proteins function in diverse processes including quorum sensing in bacteria, mitochondrial membrane fusion, apoptosis, and stem cell differentiation in eukaryotes; rhomboid proteins are also now starting to be linked to human disease, including early-onset blindness, diabetes, and parasitic diseases. Regulating cell signaling is at the heart of rhomboid protein function in many, but not all, of these processes. Further study of these novel enzymes promises to reveal the evolutionary path of rhomboid protein function, which could provide insights into the forces that drive the molecular evolution of regulatory mechanisms.

Amino Acid Sequence↗

PubMed2005

Compositional properties of random Boolean networks.

Random Boolean networks (RBNs) are used in a number of applications, including cell differentiation, immune response, evolution, gene regulatory networks, and neural networks. This paper addresses the problem of computing attractors in RBNs. An RBN with n vertices has up to 2(n) states. Therefore, for large n , computing attractors by full enumeration of states is not feasible. The state space can be reduced by removing irrelevant vertices, which have no influence on the network's dynamics. In this paper, we show that attractors of an RBN can be computed compositionally from the attractors of the independent components of the subgraph induced by the relevant vertices of the network. The presented approach reduces the complexity of the problem from O (2(n)) to O (2(l)), where l is the number of relevant vertices in the largest component.

Journal Article↗

PubMed2006

Gene duplication, exon gain and neofunctionalization of OEP16-related genes in land plants.

OEP16, a channel protein of the outer membrane of chloroplasts, has been implicated in amino acid transport and in the substrate-dependent import of protochlorophyllide oxidoreductase A. Two major clades of OEP16-related sequences were identified in land plants (OEP16-L and OEP16-S), which arose by a gene duplication event predating the divergence of seed plants and bryophytes. Remarkably, in angiosperms, OEP16-S genes evolved by gaining an additional exon that extends an interhelical loop domain in the pore-forming region of the protein. We analysed the sequence, structure and expression of the corresponding Arabidopsis genes (atOEP16-S and atOEP16-L) and demonstrated that following duplication, both genes diverged in terms of expression patterns and coding sequence. AtOEP16-S, which contains multiple G-box ABA-responsive elements (ABREs) in the promoter region, is regulated by ABI3 and ABI5 and is strongly expressed during the maturation phase in seeds and pollen grains, both desiccation-tolerant tissues. In contrast, atOEP-L, which lacks promoter ABREs, is expressed predominantly in leaves, is induced strongly by low-temperature stress and shows weak induction in response to osmotic stress, salicylic acid and exogenous ABA. Our results indicate that gene duplication, exon gain and regulatory sequence evolution each played a role in the divergence of OEP16 homologues in plants.

Amino Acid Sequence↗

PubMed2006

Sex differences in regret: all for love or some for lust?

Few sex differences in regret or counterfactual thinking are evident in past research. The authors discovered a sex difference in regret that is both domain-specific (i.e., unique to romantic relationships) and interpretable within a convergence of theories of evolution and regulatory focus. Three studies showed that within romantic relationships, men emphasize regrets of inaction over action (which correspond to promotion vs. prevention goals, respectively), whereas women report regrets of inaction and action with equivalent frequency. Sex differences were not evident in other interpersonal regrets (friendship, parental, sibling interactions) and were not moderated by relationship status. Although the sex difference was evident in regrets centering on both sexual and nonsexual relationship aspects, it was substantially larger for sexual regrets. These findings underscore the utility of applying an evolutionary perspective to better understand goal-regulating, cognitive processes.

Adolescent↗

PubMedDate not supplied

The common gammac-cytokines and transplantation tolerance.

Transplant rejection, like tolerance, is a T cell-dependent event. There is compelling evidence to suggest that induction of transplant tolerance is an actively learned process in which T cells need to engage the alloantigens in order to learn to tolerate the allograft. A family of cytokines whose receptors use the same IL-2 receptor gamma chain (also called the common gammac) plays an important role in regulating multiple aspects of the allograft response (i.e. rejection vs. tolerance). It is undeniable that gammac-cytokines can drive clonal expansion and effector maturation of alloreactive T cells, and therefore, targeting such cytokines or their receptor components remains an attractive way of blocking transplant rejection. However, we just started to appreciate that gammac-cytokines also regulate the acquisition of transplant tolerance via programming activated T cells for apoptotic cell death and via guiding the evolution of regulatory T cells. Thus, understanding precisely the role of gammac-cytokines in regulating T cell homeostasis and T cell regulation is critically important in the induction of transplant tolerance.

Animals↗

PubMed2004

The common gammac-cytokines and transplantation tolerance.

Transplant rejection, like tolerance, is a T cell-dependent event. There is compelling evidence to suggest that induction of transplant tolerance is an actively learned process in which T cells need to engage with the alloantigens in order to learn to tolerate the allograft. A family of cytokines whose receptors use the same IL-2 receptor gammac chain (also called the common gammac) plays an important role in regulating multiple aspects of the allograft response (i.e. rejection vs. tolerance). It is undeniable that gammac cytokines can drive clonal expansion and effector maturation of alloreactive T cells, and therefore, targeting such cytokines or their receptor components remains an attractive way of blocking transplant rejection. However, we just started to appreciate that gammac cytokines also regulate the acquisition of transplant tolerance via programming activated T cells for apoptotic cell death and via guiding the evolution of regulatory T cells. Thus, understanding precisely the role of gammac cytokines in regulating T cell homeostasis and T cell regulation is critically important in the induction of transplant tolerance.

Animals↗

PubMed2004

Heterogeneous evolution of the Myc-like Anthocyanin regulatory gene and its phylogenetic utility in Cornus L. (Cornaceae).

Anthocyanin is a major pigment in vegetative and floral organs of most plants and plays an important role in plant evolution. The anthocyanin regulatory genes are responsible for regulating transcription of genes in the anthocyanin synthetic pathway. To assess evolutionary significance of sequence variation and evaluate the phylogenetic utility of an anthocyanin regulatory gene, we compared nucleotide sequences of the myc-like anthocyanin regulatory gene in the genus of dogwoods (Cornus: Cornaceae). Phylogenetic analyses demonstrate that the myc-like anthocyanin regulatory gene has potential as an informative phylogenetic marker at different taxonomic levels, depending on the data set considered (DNA or protein sequences) and regions applied (exons or introns). Pairwise nonsynonymous and synonymous substitution rate tests and codon-based substitution models were applied to characterize variation and to identify sites under diversifying selection. Mosaic evolution and heterogeneous rates among different domains and sites were detected.

Anthocyanins↗

PubMed1990

The mRNA-binding protein which controls ferritin and transferrin receptor expression is conserved during evolution.

A post-transcriptional regulatory protein, termed iron regulatory factor (IRF), that binds specifically to the iron-responsive elements of ferritin and transferrin receptor mRNA, has recently been identified in the cytoplasm of human and mouse cells. Activation of this factor by low intracellular iron levels leads to inhibition of ferritin translation and an increase of TR mRNA stability. To investigate whether these feedback regulatory mechanisms are conserved during evolution, we analysed cytoplasmic extracts from 12 different species for a specific IRE-binding activity. We found mRNA-binding proteins in chicken, frog, fish and fly, which are equivalent to human and mouse IRF in gel-retardation assays with radiolabeled RNA transcripts. Competition experiments, molecular weight determinations, and modulation of the mRNA-binding activity in response to intracellular iron levels or reduction by beta-mercaptoethanol indicate that IRF has similar structural and functional properties in these different species.

Animals↗

PubMed1997

LTR retrotransposons and the evolution of eukaryotic enhancers.

Since LTR retrotransposons and retroviruses are especially prone to regional duplications and recombination events, these viral-like systems may be especially conducive to the evolution of closely spaced combinatorial regulatory motifs. Using the Drosophila copia LTR retrotransposon as a model, we show that a regulatory region contained within the element's untranslated leader region (ULR) consists of multiple copies of an 8 bp motif (TTGTGAAA) with similarity to the core sequence of the SV40 enhancer. Naturally occurring variation in the number of these motifs is correlated with the enhancer strength of the ULR. Our results indicate that inter-element selection may favor the evolution of more active enhancers within permissive genetic backgrounds. We propose that LTR retroelements and perhaps other retrotransposons constitute drive mechanisms for the evolution of eukaryotic enhancers which can be subsequently distributed throughout host genomes to play a role in regulatory evolution.

Animals↗

PubMed2003

Evolution of the TCP gene family in Asteridae: cladistic and network approaches to understanding regulatory gene family diversification and its impact on morphological evolution.

In the plant subclass Asteridae, bilaterally symmetrical flowers have evolved from a radially symmetrical ancestral phenotype on at least three independent occasions: in the Boraginaceae, Solanaceae, and Lamiales. Development of bilateral flower symmetry has been shown to be determined by the early-acting cycloidea (cyc) and dichotoma (dich) genes in Antirrhinum, a member of the Lamiales. cyc and dich belong to the TCP gene family of putative transcription factors. TCP gene sequences were isolated from 11 Asteridae taxa using an array of degenerate PCR primers. Closely related species exhibiting either ancestral actinomorphic or derived zygomorphic flowers were sampled for each independent origin of bilateral flower symmetry. Cladistic and network-based analyses were performed to establish viable hypotheses regarding the evolution of bilateral symmetry in Asteridae. For the TCP gene family, the use of cladistic phylogenetic analysis to identify orthologous genes is complicated by a paucity of alignable data, frequent gene duplication and extinction, and the possibility of reticulate evolution via intergenic recombination. These complicating factors can be generalized to many regulatory gene families. As an alternative to cladistic analysis, we propose the use of network analysis for the reconstruction of regulatory gene family phylogenetic and functional relationships. Results of analyses support the hypothesis that the origin of bilaterally symmetrical flowers in the Boraginaceae and Solanaceae did not require orthologs or functional analogs of cyc or dich. This suggests that the genetic mechanism that determines bilateral flower symmetry in these taxa is not homologous to that of the Lamiales. Results of analyses are consistent with the hypothesis that the evolution of bilateral floral symmetry in the Lamiales required the origin of a novel gene function subsequent to gene duplication.

Amino Acid Sequence↗

PubMed2006

Insect microRNAs: Structure, function and evolution.

The small regulatory non-coding RNA molecules, known as microRNAs, have been recognized as potential regulator(s) of gene expression at the post-transcriptional level. In Drosophila melanogaster, microRNAs have been identified that control important developmental processes such as apoptosis, cell division, Notch signaling, neural development and oogenesis, among others. Once activated through a step-wise maturation process, a microRNA can potentially regulate more than 50 target genes temporally and spatially in Drosophila. Thus, it is of tremendous importance to understand how these small RNA molecules have evolved and how they are expressed and regulated to impact cellular function and the associated evolutionary fitness. Studies of microRNAs in diverse insect species using the genome sequences (at least 49 insect genome sequences are in progress) may provide important clues to better understand the natural selection of microRNA genes in particular and their impact on biological functions in insects in general.

Animals↗

PubMed2002

The Otx family.

Otx1 and Otx2, the murine homologs of the Drosophila orthodenticle gene, play a remarkable role in specification and regionalization of forebrain and midbrain. Recently, genetic approaches have indicated that OTD, OTX1 and OTX2 have retained reciprocal functional equivalence in evolution, whereas their regulatory control has been remarkably modified. This suggests that during the evolution of the vertebrate brain, regulatory changes modulating the transcriptional and translational control of pre-existing gene functions might have favored the establishment of new morphogenetic pathways.

Animals↗

PubMed1997

Comparison of bicoid-dependent regulation of hunchback between Musca domestica and Drosophila melanogaster.

Co-evolution between developmental regulatory elements is an important mechanism of evolution. This work compares the hunchback-bicoid interaction in the housefly Musca domestica with Drosophila melanogaster. The Musca HUNCHBACK protein is 66% conserved and partially rescues a hunchback mutant, yet the BICOID-dependent promoter (P2) of Musca hunchback is unexpectedly diverged from D. melanogaster. Introduced into D. melanogaster, this promoter drives a normal P2 pattern during the syncytial blastoderm stage but is expressed ectopically at the anterior pole of the embryo at later stages. We also report differences in the early expression of hunchback in Musca. We suggest that conservation of the morphogenetic function of bicoid in different sized embryos of higher diptera requires co-evolution of bicoid and its target binding sites.

Amino Acid Sequence↗

PubMed2003

Evolution of transcription factors and the gene regulatory network in Escherichia coli.

The most detailed information presently available for an organism's transcriptional regulation network is that for the prokaryote Escherichia coli. In order to gain insight into the evolution of the E.coli regulatory network, we analysed information obtainable for the domains and protein families of the transcription factors and regulated genes. About three-quarters of the 271 transcription factors we identified are two-domain proteins, consisting of a DNA-binding domain along with a regulatory domain. The regulatory domains mainly bind small molecules. Many groups of transcription factors have identical domain architectures, and this implies that roughly three-quarters of the transcription factors have arisen as a consequence of gene duplication. In contrast, there is little evidence of duplication of regulatory regions together with regulated genes or of transcription factors together with regulated genes. Thirty-eight, out of the 121 transcription factors for which one or more regulated genes are known, regulate other transcription factors. This amplification effect, as well as large differences between the numbers of genes directly regulated by transcription factors, means that there are about 10 global regulators which each control many more genes than the other transcription factors.

Bacterial Proteins↗

PubMed2005

Neutral evolution of the nonbinding region of the anthocyanin regulatory gene Ipmyb1 in Ipomoea.

Plant transcription factors often contain domains that evolve very rapidly. Although it has been suggested that this rapid evolution may contribute substantially to phenotypic differentiation among species, this suggestion has seldom been tested explicitly. We tested the validity of this hypothesis by examining the rapidly evolving non-DNA-binding region of an R2R3-myb transcription factor that regulates anthocyanin expression in flowers of the genus Ipomoea. We first provide evidence that the W locus in Ipomoea purpurea, which determines whether flowers will be pigmented or white, corresponds to a myb gene segregating in southeastern U.S. populations for one functional allele and one nonfunctional allele. While the binding domain exhibits substantial selective constraint, the nonbinding region evolves at an average K(a)/K(s) ratio of 0.74. This elevated rate of evolution is due to relaxed constraint rather than to increased levels of positive selection. Despite this relaxed constraint, however, approximately 20-25% of the codons, randomly distributed throughout the nonbinding region, are highly constrained, with the remainder evolving neutrally, indicating that the entire region performs important function(s). Our results provide little indication that rapid evolution in this regulatory gene is driven by natural selection or that it is responsible for floral-color differences among Ipomoea species.

Alleles↗

PubMed1994

Correlated evolution of the cis-acting regulatory elements and developmental expression of the Drosophila Gld gene in seven species from the subgroup melanogaster.

The tissue-specific expression patterns of glucose dehydrogenase (GLD) exhibit a high degree of interspecific variation in the adult reproductive tract among the species in the genus Drosophila. We chose to focus on the evolution of GLD expression and the evolution of the Gld promoter in seven closely related species in the melanogaster subgroup as a means of elucidating the relationship of changes in cis-acting regulatory elements in the Gld promoter region with changes in tissue-specific expression. Although little variation in tissue-specific patterns of GLD was found in nonreproductive tissues during development, a surprisingly high level of variation was observed in the expression of GLD in both developing and mature reproductive organs. In some cases this variation is correlated with changes in sequence elements in the Gld promoter which were previously shown to direct tissue-specific expression in the reproductive tract. In particular D. teissieri adult males do not express GLD in their ejaculatory ducts, atypical of the melanogaster subgroup species. The Gld promoter region of D. teissieri specifically lacks all three of the TTAGA regulatory elements present in D. melanogaster. The TTAGA elements were previously shown to direct reporter gene expression to the ejaculatory duct. Together these data suggest the absence or presence of the TTAGA elements may be responsible for variation in the absence or presence of GLD in the ejaculatory duct among species.

Animals↗

PubMed1978

Regulation of newly evolved enzymes. IV. Directed evolution of the Ebg repressor.

In Escherichia coli, the wild-type repressor of ebg (evolved beta-galactosidase) enzyme synthesis, specified by the ebgR+ gene, responds very weakly to lactulose (fructose-beta-D-galactopyranoside). Selection for a functional repressor that responds strongly to lactulose as an inducer reveals the existence of ebgR+L mutants, which occur spontaneously at a frequency of about 2 X 10(-10) . EBGR+L mutants are pleiotropic in that they specify ebg repressor with a greatly increased response to lactulose, lactose, galactose-arabinoside and methyl-galactoside as inducers. Selection of ebgR+L mutants is discussed within the framework of directed evolution of a regulatory function.

Biological Evolution↗