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Results for “regulatory evolution”

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PubMed2000

RNA polymerases from Bacillus subtilis and Escherichia coli differ in recognition of regulatory signals in vitro.

Adaptation of bacterial cells to diverse habitats relies on the ability of RNA polymerase to respond to various regulatory signals. Some of these signals are conserved throughout evolution, whereas others are species specific. In this study we present a comprehensive comparative analysis of RNA polymerases from two distantly related bacterial species, Escherichia coli and Bacillus subtilis, using a panel of in vitro transcription assays. We found substantial species-specific differences in the ability of these enzymes to escape from the promoter and to recognize certain types of elongation signals. Both enzymes responded similarly to other pause and termination signals and to the general E. coli elongation factors NusA and GreA. We also demonstrate that, although promoter recognition depends largely on the sigma subunit, promoter discrimination exhibited in species-specific fashion by both RNA polymerases resides in the core enzyme. We hypothesize that differences in signal recognition are due to the changes in contacts made between the beta and beta' subunits and the downstream DNA duplex.

Amino Acid Sequence↗

PubMed2004

Region-specific onset of handling-induced changes in corticotropin-releasing factor and glucocorticoid receptor expression.

Early-life experience including maternal care profoundly influences hormonal stress responses during adulthood. Daily handling on postnatal day (P) 2-9, eliciting augmented maternal care upon returning pups to their cage, permanently modifies the expression of the stress neuromodulators corticotropin-releasing factor (CRF) and glucocorticoid receptor (GR). We have previously demonstrated reduced hypothalamic CRF expression already at the end of the handling period, followed by enhanced hippocampal GR mRNA levels (by P45). However, the initial site(s) and time of onset of these enduring changes have remained unclear. Therefore, we used semiquantitative in situ hybridization to delineate the spatiotemporal evolution of CRF and GR expression throughout stress-regulatory brain regions in handled (compared with undisturbed) pups. Enhanced CRF mRNA expression was apparent in the amygdaloid central nucleus (ACe) of handled pups already by P6. By P9, the augmented CRF mRNA levels persisted in ACe, accompanied by increased peptide expression in the bed nucleus of the stria terminalis and reduced expression in the paraventricular nucleus. The earliest change in GR consisted of reduced expression in the ACe of handled pups on P9, a time point when hippocampal GR expression was not yet affected. Thus, altered gene expression in ACe, bed nucleus of the stria terminalis as well as paraventricular nucleus may contribute to the molecular cascade by which handling (and increased maternal care) influences the stress response long term.

Aging↗

PubMed2004

Birth and evolution of the football helmet.

OBJECTIVE: To review the advent and evolution of the football helmet through historical, physiological, and biomechanical analysis. METHODS: We obtained data from a thorough review of the literature. RESULTS: Significant correlation exists between head injuries and the advent of the football helmet in 1896, through its evolution in the early to mid-1900s, and regulatory standards for both helmet use and design and tackling rules and regulations. With the implementation of National Operating Committee on Standards for Athletic Equipment standards, fatalities decreased by 74% and serious head injuries decreased from 4.25 per 100,000 to 0.68 per 100,000. Not only is the material used important, but the protective design also proves essential in head injury prevention. Competition among leading helmet manufacturers has benefited the ultimate goal of injury prevention. However, just as significant in decreasing the incidence and severity of head injury is the implementation of newer rules and regulations in teaching, coaching, and governing tackling techniques. CONCLUSION: Helmet use in conjunction with more stringent head injury guidelines and rules has had a tremendous impact in decreasing head injury severity in football. Modifications of current testing models may further improve helmet design and hence further decrease the incidence and severity of head injury sustained while playing football.

Athletic Injuries↗

PubMed1993

Proximal cis-acting elements cooperate to set Hoxb-7 (Hox-2.3) expression boundaries in transgenic mice.

The Hox genes have been proved to be instrumental in establishing the positional identity of cells along the embryonic anteroposterior (A-P) axis. Studying the regulation of these genes is a first step toward elucidating the molecular basis of regionalization during embryogenesis. We report here on the identification of cis-acting elements controlling the expression of Hoxb-7 (Hox-2.3). We show that elements driving A-P restricted gene expression are located within the 3.5 kb proximal upstream sequences of the Hoxb-7 gene. A deletion analysis provides evidence for at least three cis-acting control elements upstream from Hoxb-7, and for cooperative interactions between some of these elements in generating the A-P restricted transgenic pattern. One element, conferring by itself Hox-like expression boundaries to the transgene, has been studied in more detail and found to act in an orientation-and promoter-dependent manner. Together the 3.5 kb sequences proximal to Hoxb-7 mediate A-P restricted Hoxb-7/lacZ gene expression in a domain showing rostral boundaries more posterior than those of Hoxb-7. The evolution throughout embryogenesis of the expression pattern of a transgene carrying these sequences has been analysed and shown to mimick that of the endogenous gene, except for a slight delay in the initial expression. We conclude that the transgenes that we tested, spanning a total of 27 kb genomic sequences, do not reproduce all the features of the Hoxb-7 expression pattern. The differences in expression between Hoxb-7 and the transgenes may reveal an aspect of the Hox regulation for which either remote cis-acting control elements and/or gene clustering is required. Additional features that may have favoured maintenance of clustered organisation during evolution are partial overlap of transcription units with the regulatory regions of the neighbouring genes, and cis-regulatory interactions between multiple Hox genes: not only do cis-acting control elements of the Hoxb-7 gene map in the 3' untranslated sequences of the Hoxb-8 (Hox-2.4) gene, but our experiments suggest that Hoxb-7 control sequences modulate expression of the Hoxb-8 gene as well.

Animals↗

PubMed2003

Steroid regulation of terminal protein glycosyltransferase genes: molecular and functional homologies within sialyltransferase and fucosyltransferase families.

OBJECTIVE: Terminal glycosylations such as fucosylation and especially sialylation are crucial in maturation of proteins for their particular function. In cells and tissues where their function is under hormonal control, often terminal processes including glycosylations are tightly regulated by hormones. Therefore, it is not surprising that two key enzyme families involved in these steps, fucosyltransferases and sialyltransferases, are directly controlled by steroid hormones. METHODS: Gene structure and protein sequences have been analyzed by set of Unix-based complex sequence analysis programs of the Wisconsin GCG package, and from some other resources. Protein secondary structure predictions were based on several independent programs and applications complementing each other depending on the algorithm used, all running on Unix platforms. RESULTS: Comparison of these two types of enzymes from organisms where they are known to be under direct hormonal regulation has revealed that although sialyltransferases are broad family of proteins, the only known enzymes to be under hormonal control are alpha-2,6-sialyltransferases and in the case of fucosyl moieties transferring enzymes these are alpha-1,2/6-fucosyltransferases. Interestingly, hormonally regulated sialyltransferases from as evolutionary distant organisms as human and fruitfly share several important features including secondary structure characteristics encompassing sialyl L and S motifs in which they differ from other sialyltransferases. Analogous organizational and structural similarities were found also in hormonally regulated fucosyltransferases. CONCLUSIONS: Data indicate that hormonal control of these classes of enzymes as a regulatory mechanism could be attained relatively early during the evolution in order to obtain selective control over specific protein modification process which plays an important role during ontogenic development.

Amino Acid Sequence↗

PubMedDate not supplied

[The problem of polymorphism of GTP-binding protein subunits and its evolutionary aspects].

The data about multiplicity of isoforms of the GTP-binding protein alpha-subunits are analyzed from the point of view of their origin, functional purpose and appearance in the course of onto- and phylogenesis. An assumption is made that the polymorphism of GTP-binding protein subunits can be regarded as an important regulatory mechanism which appeared at rather late stages of evolution.

Animals↗

PubMed1995

Calpain immunoreactivity in baker's yeast, lobster and wheat germ.

The immunoreactivities of mu-calpain and m-calpain in wheat germ, lobster tail meat, and three strains of yeast were analysed by Western blotting using mouse anti-mu-calpain and rabbit anti-m-calpain. The occurrence of multiple bands may be due to either autolyses or the interactions between the calpains and other molecules. The results suggest not only a ubiquitous distribution and a universal regulatory role of calpain in eukaryotes, but also an evolutional conservation of calpain.

Animals↗

PubMed2006

Contrasting evolution of expression differences in the testis between species and subspecies of the house mouse.

Regulatory changes in genes involved in reproduction are thought to be prime targets for divergence during speciation, since they are expected to play an important role in sexual selection and sexual conflict. We used microarray analysis of RNA from different wild populations of house mouse subspecies (including Mus m. musculus, Mus m. domesticus, and Mus m. castaneus) and from the sister species Mus spretus to test this assumption. A comparison of expression divergence in brain, liver/kidney, and testis shows a major difference in the evolutionary dynamics of testis-related genes. While the comparison between species confirms an excess in divergence in testis genes, we find that all comparisons between subspecies yield only a very small number of genes with significantly different expression levels in the testis. These results suggest that the early phase of the speciation process may not be driven by regulatory changes in genes that are potential targets of sexual selection, and that the divergence in these genes is only established during a later phase of the speciation process.

Animals↗

PubMed2004

Using humans to study the physiological evolution of energy metabolism: a tribute to Peter Hochachka.

Comparative physiology traditionally relies on unusual animals to explore the mechanistic basis or evolution of physiological processes. Despite his credentials as a comparative physiologist, much of the recent work by Peter Hochachka relied upon humans as "comparative" models. Technological advances in clinical analyses and expanding databases of genomic diversity have made humans a very "convenient" model to study the evolution of metabolism. For example, a growing number of metabolic diseases have been shown to have a genetic basis. Obesity, type II diabetes, metabolic syndrome X may each have linkages to polymorphisms in genes encoding transcriptional regulators of bioenergetic genes. Genetic polymorphisms and gene families for these important transcription factors inspire questions about the evolution of energy metabolism in other animals. Thus, these biomedical studies provide important direction for researchers interested in exploring the regulatory basis of interspecies variations in bioenergetics.

Biological Evolution↗

PubMed2005

MIKC-type MADS-domain proteins: structural modularity, protein interactions and network evolution in land plants.

MIKC-type proteins represent a class of MADS-domain transcription factors and are defined by a unique domain structure: in addition to the highly conserved DNA-binding MADS-domain, they have three other domains ('I', 'K' and 'C'), with the keratin-like K-domain being the most highly conserved and characteristic one. The number and functional diversity of MIKC-type proteins increased considerably during land plant evolution, culminating in higher flowering plants, where they dominate the control of reproductive development from early to late stages. We wonder how one special class of proteins became important in the control of essentially all stages of a morphogenetic process. All MADS-domain proteins appear to bind to DNA as homo- or heterodimers and may function as part of ternary transcription factor complexes involving non-MADS-domain proteins. Only MIKC-type proteins, however, generate complex intrafamily interaction networks. These are based on the special potential of MIKC-type proteins to form complexes involving more than two homologous proteins constituting transcriptional regulators. We speculate that the potential to form heteromultimers of homologous proteins was achieved by the acquisition of the K-domain during evolution. There is emerging evidence that organismal complexity arises from progressively more elaborate regulation of gene expression. We hypothesize that combinatorial multimer formation of MIKC-type MADS-domain proteins facilitated an unusually efficient and rapid functional diversification based on gene duplication, sequence divergence and fixation. This 'networking' may have enabled a more sophisticated transcriptional control of target genes which was recruited for controlling increasingly complex and diverse developmental pathways during the rapid origin and diversification of plant reproductive structures. Therefore, MIKC-type proteins may owe their evolutionary 'success' and present-day developmental importance in part to their modular domain structure. Investigating the evolution of MIKC-type genes may thus help to better understand origin and diversification of gene regulatory networks.

Amino Acid Sequence↗

PubMed1987

[Theoretical analysis of the correspondence between the stages of evolutionary divergence and the functioning of multigene families of the immune system].

By means of phylogenetic comparison of main immunoglobulin-like multigene families (MF) and of different C-domain sequences representing them, the order of divergences of these MF in the process of evolution of the system was analysed. The order proved to be in good agreement with the ordered fashion of MF's involvement into recombinational rearrangements during the immune cell development. Indeed, according to topology of the tree for 34 C-domains, all MHC antigens are separated from the rest of Ig-like sequences, at first. Secondly, beta-chain of T-receptor is branched off the main stem of divergences, then there is a serium of divergences of CH-domains for different Ig-classes, and at last, kappa- and lambda-chains are separated. It is mu-chain of IgM which first of all branched off within an each group of isofunctional CH-sequences in the tree (CH1, CH2, CH3, CH4). The same order of events could be seen in ontogeny of the immune system. The results suggest that the appearance of a new MF of Ig-like type (or a new cluster of genetic segments within the MF) in the course of evolution could mean the addition of a new step in the regulatory system of immunologic gene expression already involved. In other words, this is unique example of recapitulation at the molecular-genetical level.

Amino Acid Sequence↗

PubMed2006

An automated method for rapid identification of putative gene family members in plants.

BACKGROUND: Gene duplication events have played a significant role in genome evolution, particularly in plants. Exhaustive searches for all members of a known gene family as well as the identification of new gene families has become increasingly important. Subfunctionalization via changes in regulatory sequences following duplication (adaptive selection) appears to be a common mechanism of evolution in plants and can be accompanied by purifying selection on the coding region. Such negative selection can be detected by a bias toward synonymous over nonsynonymous substitutions. However, the process of identifying this bias requires many steps usually employing several different software programs. We have simplified the process and significantly shortened the time required by condensing many steps into a few scripts or programs to rapidly identify putative gene family members beginning with a single query sequence. RESULTS: In this report we 1) describe the software tools (SimESTs, PCAT, and SCAT) developed to automate the gene family identification, 2) demonstrate the validity of the method by correctly identifying 3 of 4 PAL gene family members from Arabidopsis using EST data alone, 3) identify 2 to 6 CAD gene family members from Glycine max (previously unidentified), and 4) identify 2 members of a putative Glycine max gene family previously unidentified in any plant species. CONCLUSION: Gene families in plants, particularly that subset where purifying selection has occurred in the coding region, can be identified quickly and easily by integrating our software tools and commonly available contig assembly and ORF identification programs.

Arabidopsis↗

PubMed2005

Are innate immune signaling pathways in plants and animals conserved?

Although adaptive immunity is unique to vertebrates, the innate immune response seems to have ancient origins. Common features of innate immunity in vertebrates, invertebrate animals and plants include defined receptors for microbe-associated molecules, conserved mitogen-associated protein kinase signaling cascades and the production of antimicrobial peptides. It is commonly reported that these similarities in innate immunity represent a process of divergent evolution from an ancient unicellular eukaryote that pre-dated the divergence of the plant and animal kingdoms. However, at present, data suggest that the seemingly analogous regulatory modules used in plant and animal innate immunity are a consequence of convergent evolution and reflect inherent constraints on how an innate immune system can be constructed.

Adaptor Proteins, Vesicular Transport↗

PubMed2004

Design of genetic networks with specified functions by evolution in silico.

Recent studies have provided insights into the modular structure of genetic regulatory networks and emphasized the interest of quantitative functional descriptions. Here, to provide a priori knowledge of the structure of functional modules, we describe an evolutionary procedure in silico that creates small gene networks performing basic tasks. We used it to create networks functioning as bistable switches or oscillators. The obtained circuits provide a variety of functional designs, demonstrate the crucial role of posttranscriptional interactions, and highlight design principles also found in known biological networks. The procedure should prove helpful as a way to understand and create small functional modules with diverse functions as well as to analyze large networks.

Algorithms↗

PubMed1999

Establishing homology criteria for regulatory gene networks: prospects and challenges.

One of the most remarkable discoveries to emerge from the field of developmental genetics is the observation that many regulatory genes and segments of their interactive networks (pathways) appear to have been conserved in several metazoan phyla. Determining whether these conserved regulatory networks are homologous, i.e. derived from an equivalent network in the most recent common ancestor, is critical to understanding comparisons between model system studies, and the evolution of metazoan body plans. To this end, I outline some of the evolutionary properties of regulatory networks, and propose both similarity and phylogenetic criteria that can be used to test the hypothesis that two regulatory networks are homologous. Furthermore, I propose that genetic networks can be treated as a distinct level of biological organization, and can be analysed together with other hierarchical levels, such as genes, embryonic origins and morphological structures, in a comparative framework. Examples from the literature, particularly the genetic regulatory networks involved in patterning arthropod and vertebrate limbs, are examined using the proposed criteria and hierarchical approach.

Animals↗

PubMed1998

Regulation of iron metabolism in the sanguivore lamprey Lampetra fluviatilis--molecular cloning of two ferritin subunits and two iron-regulatory proteins (IRP) reveals evolutionary conservation of the iron-regulatory element (IRE)/IRP regulatory system.

Two ferritin cDNAs were cloned from the liver and spinal cord of the sanguivore lamprey Lampetra fluviatilis, an extant representative of the ancient agnathan (jawless) stage in vertebrate evolution. The deduced proteins of 20.2 kDa (H-subunit) and 20.1 kDa (M-subunit) display 73% sequence identity, and both contain the ferroxidase center characteristic of animal H-ferritin. A highly conserved iron-responsive element (IRE) was identified in the 5' untranslated region of lamprey H-ferritin. Lamprey ferritin IRE forms a specific complex with crude lamprey and rat liver extracts, and with recombinant human iron-regulatory protein (IRP-1) in an electrophoretic mobility shift assay. Furthermore, lamprey ferritin IRE competes with labeled human ferritin IRE for binding to IRP in lamprey and mammalian extracts. Two liver cDNA sequences encoding 323 residues and 101 residues of two genetically distinct lamprey IRP were amplified by PCR. Lamprey IRP-1 and IRP-2, which are 72% identical, display about 74% sequence identity to their presumed homologues in mammals. Northern blot analysis shows that two IRP transcripts of 3.6 kb and 5.8 kb are expressed in lamprey liver. Given the ancient lineage of lampreys, the results indicate that the IRE/IRP regulatory system has remained highly conserved during the evolution of vertebrates.

Amino Acid Sequence↗

PubMed2003

Rampant horizontal gene transfer and phospho-donor change in the evolution of the phosphofructokinase.

Previous work on the evolution of the phosphofructokinase (PFK) has shown that this key regulatory enzyme of glycolysis has undergone an intricate evolutionary history. Here, we have used a comprehensive data set to address the taxonomic distribution of the different types of PFK (ATP-dependent and PPi-dependent ones) and to estimate the frequency of horizontal gene transfer (HGT) events. Numerous HGT events appear to have occurred. In addition, we focused on the analysis of sites 104 and 124 (usually Gly(104)+Gly(124) or Asp(104)+Lys(124)), known to be involved in catalysis (J. Biol. Chem. 275 (2000) 35677). It revealed the existence of numerous sequences from distantly related species carrying atypical combinations of amino acids. Several adaptive changes of phospho-donors, probably requiring a single mutation at position 104, have likely occurred independently in many lineages. The analysis of this gene suggests the existence of a high rate of both HGT and substitution in its active sites. These rampant HGT events and flexibility in phospho-donor use illustrate the importance of tinkering in molecular evolution.

Animals↗

PubMed2004

Gene network polymorphism is the raw material of natural selection: the selfish gene network hypothesis.

Population genetics, the mathematical theory of modern evolutionary biology, defines evolution as the alteration of the frequency of distinct gene variants (alleles) differing in fitness over the time. The major problem with this view is that in gene and protein sequences we can find little evidence concerning the molecular basis of phenotypic variance, especially those that would confer adaptive benefit to the bearers. Some novel data, however, suggest that a large amount of genetic variation exists in the regulatory region of genes within populations. In addition, comparison of homologous DNA sequences of various species shows that evolution appears to depend more strongly on gene expression than on the genes themselves. Furthermore, it has been demonstrated in several systems that genes form functional networks, whose products exhibit interrelated expression profiles. Finally, it has been found that regulatory circuits of development behave as evolutionary units. These data demonstrate that our view of evolution calls for a new synthesis. In this article I propose a novel concept, termed the selfish gene network hypothesis, which is based on an overall consideration of the above findings. The major statements of this hypothesis are as follows. (1) Instead of individual genes, gene networks (GNs) are responsible for the determination of traits and behaviors. (2) The primary source of microevolution is the intraspecific polymorphism in GNs and not the allelic variation in either the coding or the regulatory sequences of individual genes. (3) GN polymorphism is generated by the variation in the regulatory regions of the component genes and not by the variance in their coding sequences. (4) Evolution proceeds through continuous restructuring of the composition of GNs rather than fixing of specific alleles or GN variants.

Alleles↗