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 595 records · Page 33Linked to original sources

PubMed1999

Role of the male specific lethal (msl) genes in modifying the effects of sex chromosomal dosage in Drosophila.

Immunostaining of chromosomes shows that the male-specific lethal (MSL) proteins are associated with all female chromosomes at a low level but are sequestered to the X chromosome in males. Histone-4 Lys-16 acetylation follows a similar pattern in normal males and females, being higher on the X and lower on the autosomes in males than in females. However, the staining pattern of acetylation and the mof gene product, a putative histone acetylase, in msl mutant males returns to a uniform genome-wide distribution as found in females. Gene expression on the autosomes correlates with the level of histone-4 acetylation. With minor exceptions, the expression levels of X-linked genes are maintained with either an increase or decrease of acetylation, suggesting that the MSL complex renders gene activity unresponsive to H4Lys16 acetylation. Evidence was also found for the presence of nucleation sites for association of the MSL proteins with the X chromosome rather than individual gene binding sequences. We suggest that sequestration of the MSL proteins occurs in males to nullify on the autosomes and maintain on the X, an inverse effect produced by negatively acting dosage-dependent regulatory genes as a consequence of the evolution of the X/Y sex chromosomal system.

Animals↗

PubMed1996

Angiotensin II-forming activity in a reconstructed ancestral chymase.

The current model of serine protease diversity theorizes that the earliest protease molecules were simple digestive enzymes that gained complex regulatory functions and restricted substrate specificities through evolution. Among the chymase group of serine proteases are enzymes that convert angiotensin I to angiotensin II, as well as others that simply degrade angiotensins. An ancestral chymase reconstructed with the use of phylogenetic inference, total gene synthesis, and protein expression had efficient and specific angiotensin II-forming activity (turnover number, about 700 per second). Thus, angiotensin II-forming activity is the more primitive state for chymases, and the loss of such activity occurred later in the evolution of some of these serine proteases.

Amino Acid Sequence↗

PubMed2026

Identification and characterization of the HSP gene family in the Chinese giant salamander: Expression patterns under combined environmental stress.

BACKGROUND: The Chinese giant salamander (Andrias davidianus) is a critically endangered living fossil species that is highly sensitive to changes in water temperature. However, systematic studies on the heat shock protein (HSP) gene family and its response mechanisms to environmental stress in this species remain limited. This study utilized transcriptome data from captive-bred salamanders exposed to combined temperature and pathogen stress. Bioinformatics tools were employed to identify the HSP gene family of A. davidianus (AndHSP) and to analyze their evolution, structure, and function, thereby revealing their regulatory mechanisms in response to environmental stress. RESULTS: A total of 72 AndHSPs were identified and classified into five subfamilies. Phylogenetic analysis revealed that each subfamily is evolutionarily conserved and functionally related. Gene expression analysis demonstrated that pathogen infection induced the expression of AndHSPs, and elevated temperature significantly intensified this response. Nine key differentially expressed genes were identified, predominantly from the AndHSP70 subfamily, with AndHSP70-18 exhibiting rapid heat-induced expression. Tissue-specific analysis showed high expression of AndHSP60 in the spleen. A qPCR validation confirmed the reliability of the transcriptome expression results. CONCLUSIONS: This study presents the first systematic identification of the AndHSP gene family and elucidates its cooperative stress response mechanisms under combined temperature and pathogen stress. These findings provide a molecular basis for understanding the species' environmental adaptation and have important implications for its conservation and artificial breeding.

Animals↗

PubMed2002

A comparative study of odorant binding protein genes: differential expression of the PBP1-GOBP2 gene cluster in Manduca sexta (Lepidoptera) and the organization of OBP genes in Drosophila melanogaster (Diptera).

Insects discriminate odors using sensory organs called olfactory sensilla, which display a wide range of phenotypes. Sensilla express ensembles of proteins, including odorant binding proteins (OBPs), olfactory receptors (ORs) and odor degrading enzymes (ODEs); odors are thought to be transported to ORs by OBPs and subsequently degraded by ODEs. These proteins belong to multigene families. The unique combinatorial expression of specific members of each of these gene families determines, in part, the phenotype of a sensillum and what odors it can detect. Furthermore, OBPs, ORs and ODEs are expressed in different cell types, suggesting the need for cell-cell communication to coordinate their expression. This report examines the OBP gene family. In Manduca sexta, the genes encoding PBP1Msex and GOBP2Msex are sequenced, shown to be adjacent to one another, and characterized together with OBP gene structures of other lepidoptera and Drosophila melanogaster. Expression of PBP1Msex, GOBP1Msex and GOBP2Msex is characterized in adult male and female antenna and in larval antenna and maxilla. The genomic organization of 25 D. melanogaster OBPs are characterized with respect to gene locus, gene cluster, amino acid sequence similarity, exon conservation and proximity to OR loci, and their sequences are compared with 14 M. sexta OBPs. Sensilla serve as portals of important behavioral information, and genes supporting sensilla function are presumably under significant evolutionary selective pressures. This study provides a basis for studying the evolution of the OBP gene family, the regulatory mechanisms governing the coordinated expression of OBPs, ORs and ODEs, and the processes that determine specific sensillum phenotypes.

Amino Acid Sequence↗

PubMed1994

The puzzle of Hox genes.

During the last few years, the regionalization of the rostral-caudal axis has been extensively studied through treatments with RA and genetic manipulations of Hox-C genes. RA shifts several Hox expression boundaries rostrally, deletes anterior rhombomeres but expands the caudal ones, and induces homeotic transformations in the vertebral column. These phenotypes indicate that retinoids may act in a graded fashion in the A-P axis, with maximum activity caudally. This excludes forebrain and midbrain, which apparently depend on neither Hox-C genes nor RA modulations, at least during early development. The phenotypes resulting from ectopic overexpression and loss of function of Hox genes described so far show homeotic transformations in paraxial mesoderm derivatives but not in the neurectoderm. An explanation for this discrepancy implies that the paraxial mesoderm may be already segmented in molecular terms at the time of Hox activation. Conversely, the activation of a distinct Hox-code without a previous "molecular segmentation" may specify rhombomeres with their own boundaries. This would explain why RA expands but does not duplicate the postotic rhombomeres. Finally, the atavistic transformations obtained by overexpressing Hox genes in the wrong place suggest that evolution might be introducing modifications within Hox regulatory regions. Thus, changes in their expression domains could sustain phylogenetic requirements.

Animals↗

PubMed1996

Isolation and initial characterization of the 5' flanking region of the human and murine cyclic guanosine monophosphate-phosphodiesterase beta-subunit genes.

PURPOSE: As an initial approach to study the mechanisms that direct photoreceptor-specific expression of the rod cyclic guanosine monophosphate-phosphodiesterase beta-subunit (beta-PDE) gene, the 5' flanking regions of the human and mouse genes were cloned and analyzed. METHODS: Genomic libraries were screened and clones containing the 5' upstream region of the beta-PDE gene were isolated and sequenced. Primer extension and ribonuclease protection assays were used to determine the transcription initiation sites. Sequences were compared using dot-matrix analysis and nucleotide alignment to determine potential regulatory elements that have been conserved through evolution. DNA-protein interactions were examined using DNAse I footprinting. RESULTS: The beta-PDE gene 5' sequence contains two distinct transcription start sites and lacks a TATA box. A stretch of approximately 30 nucleotides just upstream of the first transcribed nucleotide is strongly conserved in both species. This sequence contains a TATA-like element and a -CTAATC- motif previously described in other photoreceptor-specific genes. A highly-conserved AP-1 element, the recognition site for members of the jun and the fos oncoproteins family, is also present in this proximal region. DNAse I footprinting revealed an array of retinal proteins binding to these elements. CONCLUSIONS: The beta-PDE 5' region features match those of a highly tissue-specific gene in which factors restricted to the retina might play a role in gene activation. Elements conserved through evolution in the human and mouse sequences were found and analyzed as potential cis-acting elements. The availability of the human beta-PDE 5' upstream sequence will allow patients with retinal degeneration to be screened for possible mutations in these control sequences.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1995

Analysis of the ATP/GTP binding site of casein kinase II by site-directed mutagenesis.

Casein kinase II is one of only a few protein kinases which effectively utilize ATP and GTP in the phosphotransferase reaction. Two residues conserved in the ATP binding domain of other protein kinases are unique to the catalytic (alpha) subunit of casein kinase II. Val-66 is present in subdomain II and Trp-176 in subdomain VII, while > 95% of the other protein kinases contain alanine and phenylalanine, respectively. The residues in the alpha subunit of casein kinase II were changed to the conserved residues via single and double mutations by site-directed mutagenesis. These mutations enhanced the utilization of ATP over GTP by altering the K(m) values of the alpha subunit for ATP and GTP. Following reconstitution of the catalytic subunit with the regulatory (beta) subunit, both the K(m) and Vmax values of the reconstituted alpha 2 beta 2 holoenzyme were altered. Interestingly, the mutations also reduced or eliminated the 4- to 5-fold increase in catalytic activity observed with the holoenzyme over that of the alpha subunit alone. This was due to changes in secondary structure of the holoenzyme as shown by UV circular dichroism spectroscopy. Taken together, the data indicate that utilization of both ATP and GTP can be directly correlated with stimulation of catalytic activity by the regulatory subunit and suggest a co-evolution of these separate functions.

Adenosine Triphosphate↗

PubMed1996

Nuclear hormone receptors and the Drosophila ecdysone response.

In Drosophila several members of the nuclear hormone receptor super-family are involved in regulating developmental pathways mediated by the steroid hormone ecdysone. At least seven genes encode a set of receptors which are expressed in a complex overlapping temporal and tissue-specific pattern. The variety of Drosophila receptors invites comparisons with mammalian systems and suggests that different receptors may interact to regulate developmental decisions. Once again the humble fruit fly is providing a genetic framework for understanding complex regulatory systems which have been conserved during evolution.

Animals↗

PubMed2001

Molecular evolution of duplicated amylase gene regions in Drosophila melanogaster: evidence of positive selection in the coding regions and selective constraints in the cis-regulatory regions.

In this study, we randomly sampled Drosophila melanogaster from Japanese and Kenyan natural populations. We sequenced duplicated (proximal and distal) Amy gene regions to test whether the patterns of polymorphism were consistent with neutral molecular evolution. F(st) between the two geographically distant populations, estimated from Amy gene regions, was 0.084, smaller than reported values for other loci, comparing African and Asian populations. Furthermore, little genetic differentiation was found at a microsatellite locus (DROYANETSB) in these samples (G'st = -0.018). The results of several tests (Tajima's, Fu and Li's, and Wall's tests) were not significantly different from neutrality. However, a significantly higher level of fixed replacement substitutions was detected by a modified McDonald and Kreitman test for both populations. This indicates that positive selection occurred during or immediately after the speciation of D. melanogaster. Sliding-window analysis showed that the proximal region 1, a part of the proximal 5' flanking region, was conserved between D. melanogaster and its sibling species, D. simulans. An HKA test was significant when the proximal region 1 was compared with the 5' flanking region of Alcohol dehydrogenase (Adh), indicating a severe selective constraint on the Amy proximal region 1. These results suggest that natural selection has played an important role in the molecular evolution of Amy gene regions in D. melanogaster.

Alleles↗

PubMed2002

A homologue of CROC-1 in a ciliated protist (Sterkiella histriomuscorum) testifies to the ancient origin of the ubiquitin-conjugating enzyme variant family.

Resting cysts of Sterkiella histriomuscorum (Ciliophora, Oxytrichidae) have been shown to contain messenger RNA, one of which codes for a protein significantly similar to CROC-1. CROC-1 is a human regulatory protein capable of transactivating the promoter of c-fos and belongs to a newly characterized family of ubiquitin-conjugating enzyme (E2) variants (UEV). We have determined the corresponding macronuclear gene sequence, which is the first protistan UEV sequence available. The phylogenetic analysis indicates the deep separation and solid clustering of all the UEV sequences within the E2 tree showing the ancient origin of these regulatory genes and their high structural conservation during evolution. Furthermore, overexpression of the ciliate UEV is able to rescue the Saccharomyces cerevisiae mms2 null mutant from killing by DNA damaging agents, implying that the UEV family proteins are functionally conserved. In S. histriomuscorum, expression of UEV is correlated with the growth of the cells as transcripts are present in excysting and vegetative cells but are rapidly down-regulated during starvation. These data support the high conservation of the UEV family in eukaryotes, and a regulatory role of the gene is discussed in relation to known functions of UEVs. This analysis may promote the search for homologues of other regulatory genes (metazoan regulators of differentiation) in ciliates.

Amino Acid Sequence↗

PubMed2000

Impact of transposable elements on the human genome.

Presence of transposable elements (TEs) in the human genome has profound effects on genome function, structure and evolution. TE mobility and inter-TE recombination are the origin of a large spectrum of mutations and genome reorganization leading to diseases. From the data provided by the Human Genome Project and from information on the detection and dynamics of TEs within and between species acquired during the last two decades, we now know that these elements are not only involved in mutagenesis but can also participate in many cellular functions including recombination, gene regulation, protein-coding RNA messages and, possibly, cellular stress response and centromere function. TEs also promote a general genome shuffling process that has been important for the evolution of several gene families and for the development of new regulatory pathways.

Centromere↗

PubMed2003

Duplicative transfer of a MADS box gene to a plant Y chromosome.

Y chromosomes carry genes with functions in male reproduction and often have few other loci. Their evolution and the causes of genetic degeneration are of great interest. In addition to genetic degeneration, the acquisition of autosomal genes may be important in Y chromosome evolution. We here report that the dioecious plant Silene latifolia harbors a complete MADS box gene, SlAP3Y, duplicated onto the Y chromosome. This gene has no X-linked homologs but only an autosomal paralog, SlAP3A, and sequence divergence suggests that the duplication is a quite old event that occurred soon after the evolution of the sex chromosomes. Evolutionary sequence analyses using homologs of closely related species, including hermaphroditic Silene conica and dioecious Silene dioica and Silene diclinis, suggest that both SlAP3A and SlAP3Y genes encode functional proteins. Indeed, quantitative RT-PCR and in situ hybridization analyses showed that SlAP3A is expressed specifically in developing petals, but SlAP3Y is much more strongly expressed in developing stamens. The S. conica homolog, ScAP3A, is expressed in developing petals, suggesting subfunctionalization with evolution of male-specific functions, possibly due to evolutionary change in regulatory elements. Our results suggest that the acquisition of autosomal genes is an important event in the evolution of plant Y chromosomes.

Chromosomes, Plant↗

PubMed2003

Excess non-synonymous substitutions suggest that positive selection episodes occurred during the evolution of DNA-binding domains in the Arabidopsis R2R3-MYB gene family.

It has been suggested that evolutionary changes in regulatory genes may be the predominant molecular mechanism governing both physiological and morphological evolution. R2R3-AtMYB is one of the largest transcription factor gene families in Arabidopsis. Using inferred ancestral sequences we show that several lineages in the R2R3-AtMYB phylogeny experienced excess non-synonymous nucleotide substitution upon gene duplication, indicating episodes of positive selection driving adaptive shifts early in the evolution of this gene family. A noise reduction technique was then used to determine individual sites in DNA-binding domains (R2 domain and R3 domain) of R2R3-AtMYB protein sequence that were favored by frequent non-synonymous substitutions. The analyses reveal that the first helix (helix1) and the second helix (helix2) in both R2 and R3 domains are characterized by more frequent non-synonymous substitutions, and thus experienced significantly higher positive selection pressure than the third helix (helix3) in both domains. Previous MYB protein structure studies have suggested that helix1 and helix2 in both R2 and R3 domains are involved in the characteristic packing of R2R3-AtMYB DNA-binding domains. This suggests that excess non-synonymous substitutions in these helices could have resulted in MYB recognition of novel gene target sites.

Amino Acid Sequence↗

PubMed2006

Evolution of a basic helix-loop-helix protein from a transcriptional repressor to a plastid-resident regulatory factor: involvement in hypersensitive cell death in tobacco plants.

The tobacco gene NtWIN4 (Nicotiana tabacum wound-induced clone 4) is transiently up-regulated in response not only to wounding but also to pathogen attack. NtWIN4 encodes a putative basic helix-loop-helix protein with an apparent molecular mass of 28 kDa that exhibited clear nuclear transcription repression activity in Dual-Luciferase assays. However, immunoblotting indicated the existence of a 17-kDa form of NtWIN4 localized exclusively in tobacco leaf chloroplasts. Subsequent peptide dissection analyses with green fluorescent protein fusions revealed that a polypeptide of 81 amino acids starting at position 13 from the N terminus is maximally necessary for this localization. Further fine dissection analysis strongly suggested that the protein actually begins at the second Met located at position 27, yielding a signal peptide of 67 amino acids. However, the last C-terminal 15 amino acids overlap with the conserved basic region critical for DNA binding, so NtWIN4 presumably does not function as a transcription factor in planta. Transgenic tobacco plants constitutively overexpressing NtWIN4 demonstrated mortality with abnormal features, including albinism, and transient expression upon agroinfiltration resulted in distinct necrosis with a sharp decrease in chlorophyll content, consistent with the phenomenon known as chlorosis. Transgenic RNA interference tobacco plants exhibited reduced hypersensitive cell death, showing delayed tissue necrosis upon pathogen infection. These results suggest that NtWIN4 arose by divergence, becoming a chloroplast-resident factor from a nuclear transcriptional repressor by obtaining a transit peptide sequence, and that, upon translocation, it interacts with chloroplast components to induce hypersensitive cell death through chloroplast disruption, thereby contributing to plant stress responses.

Amino Acid Sequence↗

PubMed2004

Reconstruction of the evolutionary history of the LexA-binding sequence.

In recent years, the recognition sequence of the SOS repressor LexA protein has been identified for several bacterial clades, such as the Gram-positive, green non-sulfur bacteria and Cyanobacteria phyla, or the 'Alphaproteobacteria', 'Deltaproteobacteria' and 'Gammaproteobacteria' classes. Nevertheless, the evolutionary relationship among these sequences and the proteins that recognize them has not been analysed. Fibrobacter succinogenes is an anaerobic Gram-negative bacterium that branched from a common bacterial ancestor immediately before the Proteobacteria phylum. Taking advantage of its intermediate position in the phylogenetic tree, and in an effort to reconstruct the evolutionary history of LexA-binding sequences, the F. succinogenes lexA gene has been isolated and its product purified to identify its DNA recognition motif through electrophoretic mobility assays and footprinting experiments. After comparing the available LexA DNA-binding sequences with the F. succinogenes one, reported here, directed mutagenesis of the F. succinogenes LexA-binding sequence and phylogenetic analyses of LexA proteins have revealed the existence of two independent evolutionary lanes for the LexA recognition motif that emerged from the Gram-positive box: one generating the Cyanobacteria and 'Alphaproteobacteria' LexA-binding sequences, and the other giving rise to the F. succinogenes and Myxococcus xanthus ones, in a transitional step towards the current 'Gammaproteobacteria' LexA box. The contrast between the results reported here and the phylogenetic data available in the literature suggests that, some time after its emergence as a distinct bacterial class, the 'Alphaproteobacteria' lost its vertically received lexA gene, but received later through lateral gene transfer a new lexA gene belonging to either a cyanobacterium or a bacterial species closely related to this phylum. This constitutes the first report based on experimental evidence of lateral gene transfer in the evolution of a gene governing such a complex regulatory network as the bacterial SOS system.

Alphaproteobacteria↗

PubMed1996

Amino acid conservation in animal glucokinases. Identification of residues implicated in the interaction with the regulatory protein.

To delineate the regions of liver glucokinase that are involved in the binding of its regulatory protein and have therefore been conserved throughout evolution, we have cloned the cDNA of the Xenopus laevis enzyme. It contains an open reading frame of 1374 nucleotides and encodes a protein of 458 amino acids, which displays 78 and 79% overall identity to rat and human liver glucokinases, respectively. The conserved regions are predicted to be present mainly in the small domain and the hinge region of glueokinase, and the nonconserved regions in the large domain of the enzyme. We constructed five mutants of Xenopus glucokinase by replacing sets of 2-5 glucokinase-specific residues with their counterparts in the C-terminal half of rat hexokinase I. The affinity for the regulatory protein was not markedly changed for mutants B, D, and E despite a decreased affinity for glucose in mutants B and D. Two other mutants (A and C) were 9- and 250-fold less sensitive to the rat regulator and 40- and 770-fold less sensitive to the Xenopus regulator, respectively, but presented a normal affinity for glucose. The double mutant (A-C) was completely insensitive to inhibition by the regulatory protein. A control mutant (F), obtained by replacing 3 residues that were not conserved in all glucokinases, had a normal affinity for glucose and for the regulatory protein. The property of glucokinase to be inhibited by palmitoyl-CoA was not affected by the mutations described. It is concluded that His-141 to Leu-144, which are located close to the tip of the small domain, as well as Glu-51 and Glu-52, which are present in the large domain of the enzyme close to the hinge region, or nearby residues participate in the binding of the regulatory protein.

Amino Acid Sequence↗

PubMed2006

Regulatory objectivity and the generation and management of evidence in medicine.

The evolution of Western medicine since World War II has resulted in the emergence of new practices based on the direct interaction of biology and medicine. The post-war realignment of biology and medicine has been accompanied by the emergence of a new type of objectivity, regulatory objectivity, that is based on the systematic recourse to the collective production of evidence. Unlike forms of objectivity that emerged in earlier eras, regulatory objectivity consistently results in the production of conventions, sometimes tacit and unintentional but most often arrived at through concerted programs of action. These actions incorporate unprecedented levels of reflexivity, in the sense that biomedical practitioners in their debates and discussions take into account the conventional dimension of their endeavors. The conventions produced by regulatory objectivity create the conditions for a clinical objectivity that relies on the existence of entities and protocols produced and maintained far outside the intimate encounter between doctor and patient. By establishing endogenous forms of regulation, regulatory objectivity operates on a different plane and in a different mode from those suggested by analysts who treat all regulation as a form of rationalization imposed upon medicine from without.

Biomedical Research↗

PubMed2006

Evolution of microRNAs.

MicroRNAs (miRNAs) form a large class of small regulatory RNAs in eukaryotes. Although they share a common processing pathway and certain structural features, in general, there is no detectable sequence similarity among miRNAs from a given organism. On the other hand, many miRNAs are members of a family of a few, often very similar, paralogs. It is, thus, of interest to trace the evolutionary history of individual miRNAs, to identify the timing of gene duplications, and to study relationships between the histories of different miRNA families. Some miRNAs are transcribed from polycistronic primary transcripts. In these cases, we will study the evolution of entire clusters.

Base Pairing↗