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Results for “regulatory evolution”

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PubMed1997

Molecular domestication of mobile elements.

Transposable elements are ubiquitous in all organisms and represent a dynamic component of their genomes, causing mutations and thereby genetic variation. Because of their independent and expansive replication strategy, these elements are called selfish and were thought to have no impact on the adaptive evolution of their host organisms. Although most TE-induced mutations seem to exert only negative effects on the fitness of their carrier, recent evidence indicates that in the course of evolution at least some TE-mediated changes have become established features of the host genome. For example, the insertion of TEs may provide novel cis-regulatory regions to preexisting host genes or TE-derived trans-acting factors may undergo a molecular transition into novel host genes through a process described as molecular domestication. The stationary P element related gene clusters of D. guanche, D. madeirensis and D. subobscura provide an excellent model system to study the evolutionary impact of TEs on genome evolution. Each cluster unit consists of a cis-regulating section composed of different insertion sequences followed by the first three exons of a P element that are coding for a 66 kDa 'repressor-like' protein.

Animals↗

PubMed1997

Radical alterations in the roles of homeobox genes during echinoderm evolution.

Echinoderms possess one of the most highly derived body architectures of all metazoan phyla, with radial symmetry, a calcitic endoskeleton, and a water vascular system. How these dramatic morphological changes evolved has been the subject of extensive speculation and debate, but remains unresolved. Because echinoderms are closely related to chordates and postdate the protostome/deuterostome divergence, they must have evolved from bilaterally symmetrical ancestors. Here we report the expression domains in echinoderms of three important developmental regulatory genes (distal-less, engrailed and orthodenticle), all of which encode transcription factors that contain a homeodomain. Our findings show that the reorganization of body architecture involved extensive changes in the deployment and roles of homeobox genes. These changes include modifications in the symmetry of expression domains and the evolution of several new developmental roles, as well as the loss of roles conserved between arthropods and chordates. Some of these modifications seem to have evolved very early in the history of echinoderms, whereas others probably evolved during the subsequent diversification of adult and larval morphology. These results demonstrate the evolutionary lability of regulatory genes that are widely viewed as conservative.

Animals↗

PubMed1995

Molecular evolution of plasminogen activator inhibitor-1 functional stability.

Plasminogen activator inhibitor-1 (PAI-1) is a member of the serine protease inhibitor (serpin) supergene family and a central regulatory protein in the blood coagulation system. PAI-1 is unique among serpins in exhibiting distinct active and inactive (latent) conformations in vivo. Though the structure of latent PAI-1 was recently solved, the structure of the short-lived, active form of PAI-1 is not known. In order to probe the structural basis for this unique conformational change, a randomly mutated recombinant PAI-1 expression library was constructed in bacteriophage and screened for increased functional stability. Fourteen unique clones were selected, and shown to exhibit functional half-lives (T1/2S) exceeding that of wild-type PAI-1 by up to 72-fold. The most stable variant (T1/2 = 145 h) contained four mutations. Detailed analysis of these four mutations, individually and in combination, demonstrated that the markedly enhanced functional stability of the parent compound mutant required contributions from all four substitutions, with no individual T1/2 exceeding 6.6 h. The functional stability of at least eight of the remaining 13 compound mutants also required interactions between two or more amino acid substitutions, with no single variant increasing the T1/2 by > 10-fold. The nature of the identified mutations implies that the unique instability of the PAI-1 active conformation evolved through global changes in protein packing and suggest a selective advantage for transient inhibitor function.

Amino Acid Sequence↗

PubMed2001

Current problems with the zootype and the early evolution of Hox genes.

"Hox cluster type" genes have sparked intriguing attempts to unite all metazoan animals by a shared pattern of expression and genomic organization of a specific set of regulatory genes. The basic idea, the zootype concept, claims the conservation of a specific set of "Hox cluster type genes" in all metazoan animals, i.e., in the basal diploblasts as well as in the derived triploblastic animals. Depending on the data used and the type of analysis performed, different opposing views have been taken on this idea. We review here the sum of data currently available in a total evidence analysis, which includes morphological and the most recent molecular data. This analysis highlights several problems with the idea of a simple "Hox cluster type" synapomorphy between the diploblastic and triploblastic animals and suggests that the "zootype differentiation" of the Hox cluster most likely is an invention of the triploblasts. The view presented is compatible with the idea that early Hox gene evolution started with a single proto-Hox (possibly a paraHox) gene. J. Exp. Zool. (Mol. Dev. Evol.) 291:169-174, 2001.

Animals↗

PubMed1985

Suppression in Xenopus laevis: thymus inducer, spleen effector cells.

Studies were carried out on suppressor function in the amphibian Xenopus laevis, the South African clawed toad. Suppression by the thymus of haemagglutinin (HA) production by spleen is antigen-dependent, partially specific and not MHC-restricted in this species (Ruben, Buenafe & Seivert, 1983). Three questions were considered in this study. Does the thymus effect suppression by stimulating peripheralized spleen effector cells, or do effector cells reside within the thymus? Do macrophages participate in the induction and/or expression of thymus-dependent suppressor function? Can thymus suppressor and helper functions be distinguished by using irradiation treatment? The capacity of immunized thymus to suppress HA when co-cultured with spleen fragments from immunized, cyclophosphamide (CyP)-injected animals was tested. Immunized thymus failed to suppress the high levels of HA production by spleen fragments from CyP-treated, immunized donors. Colloidal carbon injection resulted in blockade of macrophage function, and both the capacity of thymuses to suppress and of spleens to be suppressed in co-cultures. Finally, the effect of thymus exposure to gamma-irradiation in vitro was tested using autogeneic thymus/spleen combinations. This enabled the visualization of thymic helper function, which is MHC-restricted in Xenopus (Bernard et al., 1981). Four dosages of irradiation were tested after antigen challenge. The highest HA titres were produced by spleen co-cultures with thymuses which had received 1000 rads. We conclude that suppression of HA production in spleen is not the result of thymus suppressor effector cells, but that suppressor function is mediated by thymus inducer cells which stimulate suppressor effectors in spleen. Both the thymic inducers and effectors in the spleen are sensitive to CyP and macrophage blockade. Our studies further suggest that we are able to distinguish between the thymic functions of help and suppression in Xenopus by taking advantage of their differential sensitivities to irradiation. While it has been postulated, on other grounds, that suppression was one of the earliest thymic regulatory functions to have evolved (L.N. Ruben & R.H. Clothier, submitted), here we suggest the presence of sequential activities of more than one cellular subset, as early in evolution as the primitive anuran (tail-less) amphibia.

Animals↗

PubMed2005

A catalog of stability-associated sequence elements in 3' UTRs of yeast mRNAs.

BACKGROUND: In recent years, intensive computational efforts have been directed towards the discovery of promoter motifs that correlate with mRNA expression profiles. Nevertheless, it is still not always possible to predict steady-state mRNA expression levels based on promoter signals alone, suggesting that other factors may be involved. Other genic regions, in particular 3' UTRs, which are known to exert regulatory effects especially through controlling RNA stability and localization, were less comprehensively investigated, and deciphering regulatory motifs within them is thus crucial. RESULTS: By analyzing 3' UTR sequences and mRNA decay profiles of Saccharomyces cerevisiae genes, we derived a catalog of 53 sequence motifs that may be implicated in stabilization or destabilization of mRNAs. Some of the motifs correspond to known RNA-binding protein sites, and one of them may act in destabilization of ribosome biogenesis genes during stress response. In addition, we present for the first time a catalog of 23 motifs associated with subcellular localization. A significant proportion of the 3' UTR motifs is highly conserved in orthologous yeast genes, and some of the motifs are strikingly similar to recently published mammalian 3' UTR motifs. We classified all genes into those regulated only at transcription initiation level, only at degradation level, and those regulated by a combination of both. Interestingly, different biological functionalities and expression patterns correspond to such classification. CONCLUSION: The present motif catalogs are a first step towards the understanding of the regulation of mRNA degradation and subcellular localization, two important processes which--together with transcription regulation--determine the cell transcriptome.

3' Untranslated Regions↗

PubMed1997

Evolution of a fetal expression pattern via cis changes near the gamma globin gene.

One basis for the evolution of organisms is the acquisition of new temporal and spatial domains of gene expression. Such novel expression domains could be generated either by cis sequence changes that alter the complement of trans-acting regulators binding to control elements or by changes in the expression patterns of one or more of the regulatory (trans) factors themselves. The gamma globin gene is a prime example of a gene that has undergone a distinct change in temporal expression at a defined time in evolution. Approximately 35-55 million years ago, the previously embryonic gamma gene acquired a fetal expression pattern. This change occurred in a simian primate ancestor after the separation of simian and prosimian primates but before the further separation of the major simian lineages; thus, the (prosimian) galago gamma gene retains the ancestral embryonic expression pattern, whereas the (simian) human gamma gene is fetal. This analysis of galago and human gamma genes in transgenic mice demonstrates that cis changes in sequences within a 4.0-kilobase region surrounding the gamma gene were responsible for the evolution of a novel fetal expression pattern in the gamma globin genes of simian primates.

Animals↗

PubMed2004

Structure, function and evolution of microbial adenylyl and guanylyl cyclases.

Cells respond to signals of both environmental and biological origin. Responses are often receptor mediated and result in the synthesis of so-called second messengers that then provide a link between extracellular signals and downstream events, including changes in gene expression. Cyclic nucleotides (cAMP and cGMP) are among the most widely studied of this class of molecule. Research on their function and mode of action has been a paradigm for signal transduction systems and has shaped our understanding of this important area of biology. Cyclic nucleotides have diverse regulatory roles in both unicellular and multicellular organisms, highlighting the utility and success of this system of molecular communication. This review will examine the structural diversity of microbial adenylyl and guanylyl cyclases, the enzymes that synthesize cAMP and cGMP respectively. We will address the relationship of structure to biological function and speculate on the complex origin of these crucial regulatory molecules. A review is timely because the explosion of data from the various genome projects is providing new and exciting insights into protein function and evolution.

Adenylyl Cyclases↗

PubMed1992

A human binding site for transcription factor USF/MLTF mimics the negative regulatory element of human immunodeficiency virus type 1.

Transcriptional regulation of the proviral form of the human immunodeficiency virus type 1 (HIV-1) is exerted by its 5' long terminal repeat (LTR), which contains recognition sites for several cell factors. By gel retardation and DNase I footprinting experiments we have identified a binding site for a human nuclear protein between nucleotides -152 to -174 upstream of transcription start site, in a region previously recognized as a negative regulator of transcription (negative regulatory element, NRE). The recognized sequence contains the dyad symmetry element CACGTG, which represents a binding motif, very conserved through evolution, present in a putative human DNA replication origin (pB48), in the upstream element of the major late promoter (MLP-UE) of adenovirus, and, as transcriptional element, upstream of many eukaryotic genes. Common binding activities exist in human nuclear extracts for pB48, MLP-UE and the HIV-1 LTR; at least three protein species recognize the LTR sequence, of 44 (corresponding to transcription factor USF/MLTF), 70, and 110 kDa, respectively. Chloramphenicol acetyltransferase assays suggest that the USF/MLTF binding site located in the HIV-1 LTR acts as a negative regulator of transcription, and that it contributes to the overall negative function exerted by the NRE. An oligonucleotide corresponding to another characterized human USF/MLTF binding site can functionally replace part of the activity of the NRE. This negative function is exerted both in presence or absence of tat transactivation, in different cell lines, and after PMA stimulation.

Adenoviruses, Human↗

PubMed2001

Mapping protein family interactions: intramolecular and intermolecular protein family interaction repertoires in the PDB and yeast.

In the postgenomic era, one of the most interesting and important challenges is to understand protein interactions on a large scale. The physical interactions between protein domains are fundamental to the workings of a cell: in multi-domain polypeptide chains, in multi-subunit proteins and in transient complexes between proteins that also exist independently. To study the large-scale patterns and evolution of interactions between protein domains, we view interactions between protein domains in terms of the interactions between structural families of evolutionarily related domains. This allows us to classify 8151 interactions between individual domains in the Protein Data Bank and the yeast Saccharomyces cerevisiae in terms of 664 types of interactions, between protein families. At least 51 interactions do not occur in the Protein Data Bank and can only be derived from the yeast data. The map of interactions between protein families has the form of a scale-free network, meaning that most protein families only interact with one or two other families, while a few families are extremely versatile in their interactions and are connected to many families. We observe that almost half of all known families engage in interactions with domains from their own family. We also see that the repertoires of interactions of domains within and between polypeptide chains overlap mostly for two specific types of protein families: enzymes and same-family interactions. This suggests that different types of protein interaction repertoires exist for structural, functional and regulatory reasons.

Binding Sites↗

PubMedDate not supplied

Expression of enhancers is altered in Drosophila melanogaster hybrids.

The molecular foundations of evolution are difficult to trace because most protein sequences are virtually identical in closely related species. The largest fraction of sequence within the genome, however, is composed of noncoding sequences where regulatory elements locate to various sites. It has been suggested that changes in the activity of these elements may trigger evolutionary change. In Drosophila, the enhancer trap procedure identifies regulatory sequences in the genome after the insertion of a P-element-based construct. We generated new insertions and characterized their expression domains in the adult eye and larval imaginal disks using the white and LacZ reporter genes. Lines with robust expression patterns in D. melanogaster were analyzed in hybrids to test the conservation of regulatory mechanisms between species. Most of the enhancers used in this study modified their expression in hybrids with the mating species D. mauritiana and D. simulans. Expression changes resulted either in gain or loss of expression and were cell-type or hybrid-genome specific. Further characterization of a limited number of enhancers in D. melanogaster showed that expression domains could adapt to changes in cell number during development but not after the completion of cell proliferation. Also, expression of some enhancers appeared to be sensitive to heterochromatin from the Y but not the X chromosome. Taken together, these results demonstrate the high sensitivity of regulatory mechanisms of gene expression as a prime source of evolutionary change and suggest quantitative changes in available transcription factors as one of the mechanisms involved.

Animals↗

PubMed1986

Interculture variation and evolution of B lineage lymphocytes in long-term bone marrow culture.

A recently described long-term culture system offers a unique experimental approach for dissecting regulatory mechanisms that control the developmental progression of B-lineage lymphocytes. Lymphoid cells, including B cells and their precursors, can be maintained for prolonged periods in strict dependence on a layer of adherent cells. However, before this system can yield to interpretable manipulation, much information is needed as to the identity and temporal phenotypic stability of both lymphoid and nonlymphoid cells. The findings reported here provide answers to some of those important questions. Successful establishment of lymphoid cells in culture was extraordinarily dependent on the batch of fetal calf serum used in the medium, and some undesirable serum lots supported cultures that were virtually all myeloid. With standardized culture conditions, various populations of lymphoid cells were identified on the basis of B-lineage differentiation markers and culture to culture variation was assessed. Lymphocytes that were firmly attached to the adherent cells were carefully compared to nonadherent lymphocytes in terms of cycle status, phenotype, size, and transferrin receptor expression. They were essentially identical in all of these respects and a partitioning of proliferating cells and their progeny in the cultures was therefore not apparent. It is also noteworthy that although a high mitotic rate was maintained, a majority of the cells were small lymphocytes. The outgrowth of identifiable B-lineage cells (detected with monoclonal 14.8 antibodies) in replicate cultures was initially similar, but the extent of interculture variation increased dramatically during the period 4-6 weeks after initiation of culture. Replicate cultures established from the same marrow cell pool often differed as much as 20-fold in numbers of 14.8-positive cells. After this time, the composition of individual cultures evolved much more gradually, and numbers of B cells and pre-B cells remained relatively constant. This indicates that subsets of lymphocytes become established in each culture dish during a discrete phase. At least two types of supporting adherent cells predominated in these cultures: typical macrophages and very large, nonphagocytic cells resembling adventitial reticular cells. The latter included subpopulations resolved on the basis of alkaline phosphatase content. In contrast to the lymphoid populations, proportions of these adherent cell types were relatively invariant among replicate cultures.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2004

The evolution of a radiation safety audit program for a research institution.

Possibly two of the greatest challenges of a radiation safety program are to ensure that all regulatory requirements are being met and to involve the users in maintaining compliance. At the Fred Hutchinson Cancer Research Center (FHCRC), the radiation safety office has developed an audit program that accomplishes these two challenges for the FHCRC ionizing radiation safety program, which has resulted in quality improvements in the laboratory environment and culminated in an excellent State inspection.

Academies and Institutes↗

PubMed1980

A theory of modular evolution for bacteriophages.

The modular theory of virus evolution has clear experimental support among the temperate bacteriophages of the enteric bacteria. However, there is also similar genetic and DNA heteroduplex evidence for such evolution among other families of bacteriophages: the virulent bacteriophages of the enterics comprise several families: the T-even group, the T3-T7 group (which has many members among different species of bacteria, including bacteria as widely divergent as E. coli and Caulobacter crescentus. It nicely explains the diffusion of very similar homologous bacteriophages into hosts whose own DNAs have diverged very greatly from each other in nucleotide sequence. It also accounts for the rigorous maintenance of regulatory schemes while units of function (including regions coding for proteins) diverge more rapidly. It should also be noted that the considerations that make modular evolution seem advantageous for bacteriophages apply equally well to viruses of higher organisms. Furthermore, the kinds of heteroduplex similarity observed among animal viruses are reminiscent of what is found for bacteriophages. Viruses found in widely divergent hosts show much greater similarity than would be expected; quite possibly animal viruses also evolve as a population of interchangeable modules.

Bacteriophage lambda↗

PubMed2005

Feedbacks and the coevolution of plants and atmospheric CO2.

The coupled evolution of land plants, CO2, and climate over the last half billion years has maintained atmospheric CO2 concentrations within finite limits, indicating the involvement of a complex network of geophysiological feedbacks. But insight into this important regulatory network is extremely limited. Here we present a systems analysis of the physiological and geochemical processes involved, identifying new positive and negative feedbacks between plants and CO2 on geological time scales. Positive feedbacks accelerated falling CO2 concentrations during the evolution and diversification of terrestrial ecosystems in the Paleozoic and enhanced rising CO2 concentrations across the Triassic-Jurassic boundary during flood basalt eruptions. The existence of positive feedbacks reveals the unexpected destabilizing influence of the biota in climate regulation that led to environmental modifications accelerating rates of terrestrial plant and animal evolution in the Paleozoic.

Biological Evolution↗

PubMedDate not supplied

Biological evolution as an expression of body-plan potentialities.

A growing bulk of recent data from different fields as molecular biology, developmental biology, genetics, paleontology and phylogenetics shows that organisms play a more active role in their evolution than what postulated by the random variation-natural selection paradigm of the neo-Darwinian synthesis. Organisms show during development and morphogenesis autopoietic processes which are related to their body-plan potentialities. These potentialities are expressed through regulatory networks in which a plastic genome participates together with proteins and other substances in an epigenetic space. The epigenetic systems which arise from this interaction may be inherited and then assume a significant role in evolution becoming the source of new acquired characters. The acquisition of new traits through the epigenetic systems is influenced directly by environmental cues. If this process is coherent with the environmental demands it co-operates with natural selection in organism adaptation. An outstanding role in this context may be played by phenotypic plasticity if, as emerges in recent views, it may constitute a general basis for genetic assimilation processes.

Animals↗

PubMed2006

Adaptive evolution of multicolored fluorescent proteins in reef-building corals.

Here we investigate the evolutionary scenarios that led to the appearance of fluorescent color diversity in reef-building corals. We show that the mutations that have been responsible for the generation of new cyan and red phenotypes from the ancestral green were fixed with the help of positive natural selection. This fact strongly suggests that the color diversity is a product of adaptive evolution. An unexpected finding was a set of residues arranged as an intermolecular binding interface, which was also identified as a target of positive selection but is nevertheless not related to color diversification. We hypothesize that multicolored fluorescent proteins evolved as part of a mechanism regulating the relationships between the coral and its algal endosymbionts (zooxanthellae). We envision that the effect of the proteins' fluorescence on algal physiology may be achieved not only through photosynthesis modulation, but also through regulatory photosensors analogous to phytochromes and cryptochromes of higher plants. Such a regulation would require relatively subtle, but spectrally precise, modifications of the light field. Evolution of such a mechanism would explain both the adaptive diversification of colors and the coevolutionary chase at the putative algae-protein binding interface in coral fluorescent proteins.

Adaptation, Biological↗

PubMed2005

Intron size and exon evolution in Drosophila.

We have found a negative correlation between evolutionary rate at the protein level (as measured by d(N)) and intron size in Drosophila. Although such a relation is expected if introns reduce Hill-Robertson interference within genes, it seems more likely to be explained by the higher abundance of cis-regulatory elements in introns (especially first introns) in genes under strong selective constraints.

Animals↗