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 415 records · Page 23Linked to original sources

PubMed1995

Molecular evolution of flower development: diversification of the plant MADS-box regulatory gene family.

Floral homeotic genes that control the specification of meristem and organ identity in developing flowers have been isolated from both Arabidopsis thaliana and Antirrhinum majus. Most of these genes belong to a large family of regulatory genes and possess a characteristic DNA binding domain known as the MADS-box. Members of this gene family display primarily floral-specific expression and are homologous to transcription factors found in several animal and fungal species. Molecular evolutionary analyses reveal that there are appreciable differences in the substitution rates between different domains of these plant MADS-box genes. Phylogenetic analyses also demonstrate that members of the plant MADS-box gene family are organized into several distinct gene groups: the AGAMOUS, APETALA3/PISTILLATA and APETALA1/AGL9 groups. The shared evolutionary history of members of a gene group appear to reflect the distinct functional roles these MADS-box genes play in flower development. Molecular evolutionary analyses also suggest that these different gene groups were established in a relatively short span of evolutionary time and that the various floral homeotic loci originated even before the appearance of the flowering plants.

Amino Acid Sequence↗

PubMed2000

Expression of achaete-scute homologues in discrete proneural clusters on the developing notum of the medfly Ceratitis capitata, suggests a common origin for the stereotyped bristle patterns of higher Diptera.

The stereotyped positioning of sensory bristles in Drosophila has been shown to result from complex spatiotemporal regulation of the proneural achaete-scute genes, that relies on an array of cis-regulatory elements and spatially restricted transcriptional activators such as Pannier. Other species of derived schizophoran Diptera have equally stereotyped, but different, bristle patterns. Divergence of bristle patterns could arise from changes in the expression pattern of proneural genes, resulting from evolution of the cis-regulatory sequences and/or altered expression patterns of transcriptional regulators. Here we describe the isolation of achaete-scute homologues in Ceratitis capitata, a species of acalyptrate Schizophora whose bristle pattern differs slightly from that of Drosophila. At least three genes, scute, lethal of scute and asense have been conserved, thus demonstrating that gene duplication within the achaete-scute complex preceded the separation of the families Drosophilidae and Tephritidae, whose common ancestor goes back more than 100 million years. The expression patterns of these genes provide evidence for conservation of many cis-regulatory elements as well as a common origin for the stereotyped patterns seen on the scutum of many Schizophora. Some aspects of the transcriptional regulation have changed, however, and correlate in the notum with differences in the bristle pattern. The Ceratitis pannier gene was isolated and displays a conserved expression domain in the notum.

Amino Acid Sequence↗

PubMed2026

The genomic alchemist's arsenal: A comprehensive review of gene recruitment, regulatory rewiring, and the evolutionary arms race in snake envenomation.

Snake venom represents a striking example of evolutionary innovation, in which ancestral physiological gene networks have been co-opted into potent biochemical weapons. Advances in multi-omics, single-cell genomics, and structural bioinformatics have catalyzed a conceptual shift from descriptive toxin cataloging to a systems-level understanding of venom evolution, regulation, and function. This Review integrates genomic, cellular, and structural perspectives to delineate the molecular architecture underpinning venom diversification and target-site co-evolution. Emphasis is placed on regulatory mechanisms driving rapid expression plasticity, including super-enhancer activity, transposable element insertion, spatial heterogeneity within the venom gland, and non-coding RNA-mediated modulation. At the protein level, the review examines how hypervariable toxins engage in structural arms races with prey targets, and how multi-toxin complex formation, functional synergy, and molecular dynamics simulations inform models of lethality and resistance. A comparative framework is provided by contrasting high-potency predatory snake venoms with low-potency defensive venoms of hymenopterans such as bees and wasps, revealing how ecological selective pressures shape toxin potency, composition, and target specificity across taxa. Finally, current translational strategies are evaluated, with a focus on the relative merits of recombinant human monoclonal antibodies versus catalytic-site small-molecule inhibitors as deployable interventions for snakebite. By synthesizing evolutionary genomics, structural biology, comparative toxinology, and synthetic antivenomics, this Review outlines a predictive framework for anticipating venom evolutionary trajectories and for designing broad-spectrum, next-generation therapeutics.

Animals↗

PubMed2006

Cyanobacterial two-component proteins: structure, diversity, distribution, and evolution.

A survey of the already characterized and potential two-component protein sequences that exist in the nine complete and seven partially annotated cyanobacterial genome sequences available (as of May 2005) showed that the cyanobacteria possess a much larger repertoire of such proteins than most other bacteria. By analysis of the domain structure of the 1,171 potential histidine kinases, response regulators, and hybrid kinases, many various arrangements of about thirty different modules could be distinguished. The number of two-component proteins is related in part to genome size but also to the variety of physiological properties and ecophysiologies of the different strains. Groups of orthologues were defined, only a few of which have representatives with known physiological functions. Based on comparisons with the proposed phylogenetic relationships between the strains, the orthology groups show that (i) a few genes, some of them clustered on the genome, have been conserved by all species, suggesting their very ancient origin and an essential role for the corresponding proteins, and (ii) duplications, fusions, gene losses, insertions, and deletions, as well as domain shuffling, occurred during evolution, leading to the extant repertoire. These mechanisms are put in perspective with the different genetic properties that cyanobacteria have to achieve genome plasticity. This review is designed to serve as a basis for orienting further research aimed at defining the most ancient regulatory mechanisms and understanding how evolution worked to select and keep the most appropriate systems for cyanobacteria to develop in the quite different environments that they have successfully colonized.

Bacterial Proteins↗

PubMed2004

Comparative sequence analysis of the Gdf6 locus reveals a duplicon-mediated chromosomal rearrangement in rodents and rapidly diverging coding and regulatory sequences.

Duplicated segments of genomic DNA can catalyze both gene evolution and chromosome evolution. Here we describe a rodent-specific duplication involving the Uqcrb gene, a cis-regulatory element for the Gdf6 gene, and a chromosomal rearrangement. Comparisons of Gdf6 sequences from several placental mammals and platypus revealed many strongly conserved regions flanking Gdf6 and the adjacent Uqcrb gene. However, in rat and mouse a synteny break resides approximately 70 kb upstream of Gdf6, such that Gdf6 and Uqcrb are on separate chromosomes. In rodents, Gdf6 and Uqcrb are both associated with homologous duplicons that may have catalyzed a rearrangement separating the two genes. However, the duplicon spanned both Uqcrb and a cis-regulatory element that controls Gdf6 transcription in limb skeletal joints. In mouse and rat, one duplicon now contains a degrading Uqcrb pseudogene but retains strongly conserved sequences within a Gdf6 enhancer. In contrast, the other duplicon has retained the intact Uqcrb gene and (in mouse) a copy of the Gdf6 enhancer that has acquired novel mutations. The duplicons have separately maintained distinct functions of the ancestral sequence, consistent with a "subfunction partitioning" evolutionary model. These findings also provide an example of a duplication that mobilized a tissue-specific enhancer from its cognate gene, and new evidence that duplications can be associated with chromosomal rearrangements. Furthermore, these data suggest that segmental duplications could lead to evolution of novel gene expression patterns via diversification of regulatory elements.

Animals↗

PubMed2000

Functional evolution of the Ultrabithorax protein.

The Hox genes have been implicated as central to the evolution of animal body plan diversity. Regulatory changes both in Hox expression domains and in Hox-regulated gene networks have arisen during the evolution of related taxa, but there is little knowledge of whether functional changes in Hox proteins have also contributed to morphological evolution. For example, the evolution of greater numbers of differentiated segments and body parts in insects, compared with the simpler body plans of arthropod ancestors, may have involved an increase in the spectrum of biochemical interactions of individual Hox proteins. Here, we compare the in vivo functions of orthologous Ultrabithorax (Ubx) proteins from the insect Drosophila melanogaster and from an onychophoran, a member of a sister phylum with a more primitive and homonomous body plan. These Ubx proteins, which have been diverging in sequence for over 540 million years, can generate many of the same gain-of-function tissue transformations and can activate and repress many of the same target genes when expressed during Drosophila development. However, the onychophora Ubx (OUbx) protein does not transform the segmental identity of the embryonic ectoderm or repress the Distal-less target gene. This functional divergence is due to sequence changes outside the conserved homeodomain region. The inability of OUbx to function like Drosophila Ubx (DUbx) in the embryonic ectoderm indicates that the Ubx protein may have acquired new cofactors or activity modifiers since the divergence of the onychophoran and insect lineages.

Amino Acid Sequence↗

PubMed1997

Why are Hox genes clustered?

The evolutionarily conserved genomic organization of the Hox genes has been a puzzle ever since it was discovered that their order along the chromosome is similar to the order of their functional domains along the antero-posterior axis. Why has this colinearity been maintained throughout evolution? A close look at regulatory sequences from the mouse Hox clusters suggests that enhancer sharing between adjacent Hox genes may be one reason. Moreover, characterizing the activity of one of these mouse enhancers in Drosophila illustrates that despite many similarities, not all Hox clusters are built in the same way.

Animals↗

PubMed2006

Checkpoints in memory B-cell evolution.

We consider four sequential phases in the evolution and consolidation of high affinity B-cell memory as it is regulated in a cognate manner by antigen-specific T-helper (Th) cells. Sequential developmental checkpoints control cell fate in each phase of the pathway in ways that still remain poorly understood. The cellular composition and molecular attributes of each checkpoint are of great interest, but they may vary substantially depending on the nature of the immune stimulus. How this stimulus cascades through the innate and then the adaptive immune responses defines initial effector mechanisms in both Th and B-cell compartments. The germinal center reaction controls memory B-cell development with roles for antigen presentation and cognate Th cell regulation in the establishment of the memory B-cell compartment. Antigen re-challenge rapidly promotes effector responses from the memory compartments of both Th and B cells. Importantly, re-challenge also expands and consolidates immune memory at the serological and cellular levels. We review recent advances in our understanding of memory B-cell evolution with emphasis on the regulatory checkpoints that control lymphocyte fate at each developmental juncture.

Animals↗

PubMed2006

Studying statistical properties of regulatory DNA sequences, and their use in predicting regulatory regions in the eukaryotic genomes.

There are no well-known properties in regulatory DNA analogous to those in coding sequences; their spatial location is not regular, the consensus regulatory elements are often degenerate and there are no understandable rules governing their evolution. This makes it difficult to recognize regulatory regions within genome. We review developments in the statistical characterization of regulatory regions and methods of their recognition in eukaryotic genomes.

Computational Biology↗

PubMed2005

My favorite animal, Trichoplax adhaerens.

Trichoplax adhaerens is more simply organized than any other living metazoan. This tiny marine animal looks like a irregular "hairy plate" ("tricho plax") with a simple upper and lower epithelium and some loose cells in between. After its original description by F.E. Schulze 1883, it attracted particular attention as a potential candidate representing the basic and ancestral state of metazoan organization. The lack of any kind of symmetry, organs, nerve cells, muscle cells, basal lamina and extracellular matrix originally left little doubt about the basal position of T. adhaerens. Nevertheless, the interest of zoologists and evolutionary biologists suddenly vanished for more than half a century when Trichoplax was claimed to be an aberrant hydrozoan planula larva. Recently, Trichoplax has been rediscovered as a key species for unraveling early metazoan evolution. For example, research on regulatory genes and whole genome sequencing promise insights into the genetics underlying the origin and development of basal metazoan phyla. Trichoplax offers unique potential for understanding the minimal requirements of metazoan animal organization.

Animals↗

PubMed2001

Complexity and tinkering.

All recent results in the fields of development and evolution point to a role of regulatory circuits as a major cause of evolutionary changes.

Animals↗

PubMed2006

[Evaluation of regulatory policies: the prevention of traffic accidents in Spain].

Traffic accident injuries may be reduced with public policies. We review regulatory policies extending beyond the health sector by studying the case of traffic accident injuries. They have been the object of other analyses in Spain by both health professionals and professionals from other sectors, but we have not found a previous thorough review including regulatory aspects. We analyze the evolution of fatal victims of traffic accidents as collected by the Dirección General de Tráfico, stratifying for pedestrians, two-wheel vehicle occupants and occupants of other vehicles, and breaking down accidents between those occurring in roads and in urban settings. Despite the increase in exposure factors between 1970 and 2003, we observe a strong impact of regulatory policies in accident mortality. A favorable impact is seen for regulations and enforcement actions on motorcycle helmets, speed limits and the control of alcohol use, and a lower impact for safety belts, perhaps because its actual effective implementation was not equally sharp. The adoption of comprehensive plans or complex legislation packages seems to have had a positive impact, perhaps attributable to its triggering of more effective enforcement of already existing regulations. Although the existence of legal norms is not enough in itself, as its impact is low without active enforcement, compliance improves over time. In any case, the existence of specific initiatives to influence this field is important to obtain the best results of regulatory policies in public health.

Accident Prevention↗

PubMed1999

Patterns of molecular evolution among paralogous floral homeotic genes.

The plant MADS-box regulatory gene family includes several loci that control different aspects of inflorescence and floral development. Orthologs to the Arabidopsis thaliana MADS-box floral meristem genes APETALA1 and CAULIFLOWER and the floral organ identity genes APETALA3 and PISTILLATA were isolated from the congeneric species Arabidopsis lyrata. Analysis of these loci between these two Arabidopsis species, as well as three other more distantly related taxa, reveal contrasting dynamics of molecular evolution between these paralogous floral regulatory genes. Among the four loci, the CAL locus evolves at a significantly faster rate, which may be associated with the evolution of genetic redundancy between CAL and AP1. Moreover, there are significant differences in the distribution of replacement and synonymous substitutions between the functional gene domains of different floral homeotic loci. These results indicate that divergence in developmental function among paralogous members of regulatory gene families is accompanied by changes in rate and pattern of sequence evolution among loci.

Arabidopsis↗

PubMed2006

Frontal nasal prominence expression driven by Tcfap2a relies on a conserved binding site for STAT proteins.

The AP-2 transcription factor family is linked with development of the head and limbs in both vertebrate and invertebrate species. Recent evidence has also implicated this gene family in the evolution of the neural crest in chordates, a critical step that allowed the development and elaboration of the vertebrate craniofacial skeleton. In mice, the inappropriate embryonic expression of one particular AP-2 gene, Tcfap2a, encoding AP-2alpha, results in multiple developmental abnormalities, including craniofacial and limb defects. Thus, Tcfap2a provides a valuable genetic resource to analyze the regulatory hierarchy responsible for the evolution and development of the face and limbs. Previous studies have identified a 2-kilobase intronic region of both the mouse and human AP-2alpha locus that directs expression of a linked LacZ transgene to the facial processes and the distal mesenchyme of the limb bud in transgenic mice. Further analysis identified two highly conserved regions of approximately 200-400 bp within this tissue-specific enhancer. We have now initiated a transgenic and biochemical analysis of the most important of these highly conserved regions. Our analysis indicates that although the sequences regulating face and limb expression have been integrated into a single enhancer, different cis-acting sequences ultimately control these two expression domains. Moreover, these studies demonstrate that a conserved STAT binding site provides a major contribution to the expression of Tcfap2a in the facial prominences.

Animals↗

PubMed2003

A peek into the evolution of the sexual lifestyles of yeast.

Tsong et al. characterize the role of mating type genes in Candida albicans and identify a new regulator of mating type and several mating type target genes. Comparison with Saccharomyces cerevisiae provides an in-depth view into the evolution of a well-characterized genetic regulatory circuit.

Candida albicans↗

PubMed2005

Expression patterns of developmental regulatory genes show comparable divisions in the telencephalon of Xenopus and mouse: insights into the evolution of the forebrain.

In this study, we review data on the existence of comparable divisions and subdivisions in the telencephalon of different groups of tetrapods based on expression of some developmental regulatory genes, having a particular focus in the comparison of the anuran amphibian Xenopus and the mouse. The available data on Xenopus, mouse, chick and turtle indicate that apparently all tetrapod groups possess the same molecularly distinct divisions and subdivisions in the telencephalon. This basic organization was likely present in the telencephalon of stem tetrapods. Each division/subdivision is characterized by expression of a unique combination of developmental regulatory genes, and appears to represent a self-regulated and topologically constant histogenetic brain compartment that gives rise to specific groups of cells. This interpretation has an important consequence for searching homologies, since a basic condition for cell groups in different vertebrates to be considered homologous is that they originate in the same compartment. However, evolution may allow individual cell groups derived from comparable (field homologous) subdivisions to be either similar or dissimilar across the vertebrate groups, giving rise to several possible scenarios of evolution, which include both the evolutionary conservation of similar (homologous) cells or the production of novel cell groups. Finally, available data in the lamprey, a jawless fish, suggest that not all telencephalic subdivisions were present at the origin of vertebrates, raising important questions about their evolution.

Animals↗

PubMed2003

Molecular evolution of nucleoside diphosphate kinase genes: conserved core structures and multiple-layered regulatory regions.

Genomic data regarding the nucleoside diphosphate (NDP) kinase genes have been accumulated from diverged phyla. Comparison of their regulatory sequences have shed light on the multiple facets of gene regulation systems. Phylogenetic studies, including CpG island and intron-mapping, and homologous sequence comparison, have suggested that the regions of the major mammalian genes, the ortholog (rat alpha or nm23-H2) and its paralog (rat beta or nm23-H1), have been constructed by a stepwise gain and loss of alien genes resulting in "multiple-layered" regulatory systems. They contain representative cis-elements for the constitutive, stage/lineage-specific, and early response expression. These elements' binding capacities to nuclear proteins were confirmed by electrophoretic mobility shift assay. Further, these regulatory systems generate heterogeneous mRNA at the 5' untranslated region, which influences their own translation efficiencies. In terms of this process, the transcription system would control another layer of gene expression: posttranscriptional (translational) regulation.

Amino Acid Sequence↗

PubMed1985

Apparent gene conversion between beta-tubulin genes yields multiple regulatory pathways for a single beta-tubulin polypeptide isotype.

We have determined the complete nucleotide sequences of two chicken beta-tubulin genes, beta 1 and beta 2. These genes display an unusual pattern of segmental homology which indicates that they originally arose by gene duplication and have subsequently coevolved by a process that included localized gene conversion or intergenic recombination. Since the beta-tubulin polypeptides encoded by the two genes are virtually identical (99.5%), particularly in the major beta-tubulin isotype defining regions, they almost certainly constitute a single isotypic class of beta tubulin. However, the regulatory properties of the two genes are highly divergent as indicated by analysis of their patterns of expression in different chicken cell types. beta 1 is the major transcript detected in skeletal muscle myoblasts, whereas beta 2 is the major beta-tubulin transcript in cultured sympathetic neurons. The existence of these two genes appears to derive from a regulatory requirement whereby the expression of a single tubulin isotype is mediated through different regulatory programs in development and differentiation. These results thus provide direct experimental support for the hypothesis that gene conversion and intergenic recombination play an important role in evolution by uncoupling the evolution of structural genes from the regulatory sequences which control them.

Amino Acid Sequence↗