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At least 1,711 records · Page 95Linked to original sources
PubMed2003

Evolution of C4 phosphoenolpyruvate carboxylase.

C4 plants are known to be of polyphyletic origin and to have evolved independently several times during the evolution of angiosperms. This implies that the C4 isoform of phosphoenolpyruvate carboxylase (PEPC) originated from a nonphotosynthetic PEPC gene that was already present in the C3 ancestral species. To meet the special requirements of the C4 photosynthetic pathway the expression program of the C4 PEPC gene had to be changed to achieve a strong and selective expression in leaf mesophyll cells. In addition, the altered metabolite concentrations around C4 PEPC in the mesophyll cytoplasm necessitated changes in the enzyme's kinetic and regulatory properties. To obtain insight into the evolutionary steps involved in these altered enzyme characteristics, and even the order of these steps, the dicot genus Flaveria (Asteraceae) appears to be the experimental system of choice. Flaveria contains closely related C3, C3-C4, and C4 species that can be ordered by their gradual increase in C4 photosynthetic traits. The C4 PEPC of F. trinervia, which is encoded by the ppcA gene class, possesses typical kinetic and regulatory features of a C4-type PEPC. Its nearest neighbor is the orthologous ppcA gene of the C3 species F. pringlei. This latter gene encodes a typical nonphotosynthetic C3-type PEPC which is believed to be similar to the C3 ancestral PEPC. This pair of orthologous PEPCs has been used to map C4-specific molecular determinants for the kinetic and regulatory characteristics of C4 PEPCs. The most notable finding from these investigations was the identification of a C4 PEPC invariant site-specific mutation from alanine (C3) to serine (C4) at position 774 that was a necessary and late step in the evolution of C3 to C4 PEPC. The C3-C4 intermediate ppcA PEPCs are used to identify the sequence of events leading from a C3- to a C4-type PEPC.

Amino Acid Sequence↗
PubMed1990

DNA methylation: evolution of a bacterial immune function into a regulator of gene expression and genome structure in higher eukaryotes.

The amino acid sequence of mammalian DNA methyltransferase has been deduced from the nucleotide sequence of a cloned cDNA. It appears that the mammalian enzyme arose during evolution via fusion of a prokaryotic restriction methyltransferase gene and a second gene of unknown function. Mammalian DNA methyltransferase currently comprises an N-terminal domain of about 1000 amino acids that may have a regulatory role and a C-terminal 570 amino acid domain that retains similarities to bacterial restriction methyltransferases. The sequence similarities among mammalian and bacterial DNA cytosine methyltransferases suggest a common evolutionary origin. DNA methylation is uncommon among those eukaryotes having genomes of less than 10(8) base pairs, but nearly universal among large-genome eukaryotes. This and other considerations make it likely that sequence inactivation by DNA methylation has evolved to compensate for the expansion of the genome that has accompanied the development of higher plants and animals. As methylated sequences are usually propagated in the repressed, nuclease-insensitive state, it is likely that DNA methylation compartmentalizes the genome to facilitate gene regulation by reducing the total amount of DNA sequence that must be scanned by DNA-binding regulatory proteins. DNA methylation is involved in immune recognition in bacteria but appears to regulate the structure and expression of the genome in complex higher eukaryotes. I suggest that the DNA-methylating system of mammals was derived from that of bacteria by way of a hypothetical intermediate that carried out selective de novo methylation of exogenous DNA and propagated the methylated DNA in the repressed state within its own genome.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed2004

Identifying polymorphisms in the Rattus norvegicus D3 dopamine receptor gene and regulatory region.

The D(3) dopamine receptor has been implicated in several neuropsychiatric disorders, including schizophrenia, Parkinson's disease and addiction. Sequence variation in the D(3) gene can lead to subtle alteration in receptor structure or gene expression and thus to a different phenotype. In this study we examine the sequence variation in the D(3) gene in 96 rat strains and substrains. Interestingly, the analyses revealed 10 polymorphisms in the 5'flanking region and four polymorphisms in intronic regions of the gene. Moreover, two single nucleotide polymorphisms (SNPs) that result in amino acid changes were found in the last exon of the D(3) gene in the RNU/Mol strain. Additionally, bioinformatic analysis of the 5'flanking region and first intron of the gene revealed putative transcription factor binding sites that are conserved between mouse and human and are affected by the SNPs, possibly resulting in altered regulation of the subsequent transcription factor.

5' Flanking Region↗
PubMed2006

Evolution of alternative transcriptional circuits with identical logic.

Evolution of gene regulation is an important contributor to the variety of life. Here, we analyse the evolution of a combinatorial transcriptional circuit composed of sequence-specific DNA-binding proteins that are conserved among all eukaryotes. This circuit regulates mating in the ascomycete yeast lineage. We first identify a group of mating genes that was transcriptionally regulated by an activator in a fungal ancestor, but is now transcriptionally regulated by a repressor in modern bakers' yeast. Despite this change in regulatory mechanism, the logical output of the overall circuit remains the same. By examining the regulation of mating in modern yeasts that are related to different extents, we deduce specific, sequential changes in both cis- and trans-regulatory elements that constitute the transition from positive to negative regulation. These changes indicate specific mechanisms by which fitness barriers were traversed during the transition.

Amino Acid Sequence↗
PubMed1998

Gene silencing in plants: relevance for genome evolution and the acquisition of genomic methylation patterns.

Transgenes often become silenced in plants because of repressive influences exerted by flanking plant DNA and/or because of interactions among multiple copies of closely linked transgenes. Repeated transgenes on different chromosomes can also interact in a way that leads to silencing and methylation, suggesting a previously unrecognized ability of unlinked homologous sequences to cross-talk in complex genomes. Non-Mendelian inheritance is a frequent consequence of these interactions because the silenced genes do not fully reactivate or lose methylation after segregating in progeny. Several examples of gene silencing in plants appear to reflect the action of genome defence system that methylates and inactivates foreign or invasive sequences such as transgenes and transposable elements. Because certain types of transposable elements are embedded in regulatory regions of plant genes and have become greatly amplified in plant genomes, they could contribute substantially to normal gene expression and to the generation of genomic methylation patterns. Polyploidy, which has been a major force in plant and vertebrate evolution, might encourage proliferation of transposable elements because genes in polyploids are duplicated and hence less susceptible to the consequences of insertional mutagenesis. Accordingly, the appearance of genome-wide methylation has often coincided with episodes of polyploidization.

DNA Methylation↗
PubMed1998

Evolution of the androgen receptor: structure-function implications.

To shed light on the nature and evolution of structure-function relations in the androgen receptor (AR), we have undertaken a comparative analysis of all available AR and other steroid receptor sequences. We have identified a group of amino acids that "diagnose" the clade of androgen receptors--residues that are strictly conserved among the ARs but not shared with other receptors. We hypothesize that these amino acids, clustered in a few regions of the protein, confer upon the androgen receptor its unique functions, including recognition of specific DNA response elements and affinity for androgens, rather than other steroid hormones. The four domains of the AR display markedly different rates of evolutionary divergence; conserved portions of the sequence, including small stable stretches within otherwise divergent regions, may be essential to receptor function. Current data from experimental, crystallographic, and clinical studies support these hypotheses, which can now be further tested in the laboratory.

Amino Acid Substitution↗
PubMed2002

The crocodilian mitochondrial control region: general structure, conserved sequences, and evolutionary implications.

We present the first comprehensive analysis of the crocodilian control region. We have analyzed sequences from all three families of Crocodylia (Crocodylidae, Gavialidae, Alligatoridae), incorporating all genera except Paleosuchus and Melanosuchus. Within the control region of other vertebrates, several sequence motifs and their order appear to be conserved. Herein, we compare aligned crocodilian D-loop sequences to homologous sequences from other vertebrates ranging from fish to birds. Among other findings, we have discovered that while domain I tends to be shorter than the same region in mammals and birds, it contains sequences similar in structure to both the goose-hairpin and termination associated sequences (TAS). Domain II is highly conservative with regard to size among the taxa examined and contains several of the conserved sequence boxes characterized in other vertebrates. Domain III contains several interesting sequence motifs including tandemly repeated sequences, a long poly-A region in the Crocodylidae, and possible bidirection promoter sequences.

Alligators and Crocodiles↗
PubMed2000

The MADS-Box factor CeMEF2 is not essential for Caenorhabditis elegans myogenesis and development.

MEF2 is an evolutionarily conserved MADS (MCM1, Agamous, Deficiens, and serum response factor) box-type transcription factor that plays a critical role in vertebrate and Drosophila melanogaster myogenesis. We have addressed the developmental role of the single MEF2-like factor, CeMEF2, in Caenorhabditis elegans. Using expression assays and two mef-2 deletion alleles, we show that CeMEF2 is not required for proper myogenesis or development. Moreover, a putative null mef-2 allele fails to enhance or suppress the phenotypes of mutants in CeMyoD or CeTwist. Our results suggest that despite its evolutionary conservation of sequence and DNA binding properties, CeMEF2 has adopted a divergent role in development in the nematode compared with Drosophila and vertebrates.

Amino Acid Sequence↗
PubMed1999

Guinea pig p53 mRNA: identification of new elements in coding and untranslated regions and their functional and evolutionary implications.

We report the sequence of the guinea pig p53 cDNA. The comparative analysis of the coding and noncoding regions of p53 cDNAs of all available complete vertebrate sequences has allowed us to single out new conserved signals possibly involved in p53 functional activity. We have focused our attention on the most variable region of the protein, the proline (P)-rich domain, suggested to play a fundamental role in antiproliferative pathways. In this domain we have identified the PXXXXP repeated motif and singled out a common consensus sequence that can be considered a signature for mammalian p53: PXXXXPX{0,4}PX{0,9}PA(T,P,I,)(S,P)WPL. We have demonstrated the significance of the PXXXXP motif in SH3-binding protein and suggested its structure to be a loop. Also, the 5' and 3' untranslated regions (UTRs) of the guinea pig were sequenced, and this study represents the first detailed structural analysis of the UTRs of the p53 mRNAs available in literature. The 5' UTR of guinea pig (233 nt) can be folded into a stable secondary structure resembling that predicted in mouse. The 3' UTR of guinea pig is 771 nt long and shows higher similarity with human than with rodent sequences, having a region of about 350 nt that is deleted in rat and mouse. In the 3' UTR we have identified the presence of a mammalian-wide interspersed repeat sequence and of a cytoplasmic polyadenylation element, which could be involved in translational activation by promoting polyadenylation of mRNA, providing information about a possible mechanism of regulation of p53 expression mediated by the 3' UTR of the mRNA. The observations presented here could open new avenues to targeted mutations and experimental approaches useful in investigating new regulation mechanisms of p53 translation, activity, and stability.

3' Untranslated Regions↗
PubMed1995

Aura virus is a New World representative of Sindbis-like viruses.

Aura virus is an alphavirus present in Brazil and Argentina that is serologically related to Sindbis virus (present throughout the Old World) and to Western equine encephalitis (WEE) virus (present in the Americas). We have previously shown that WEE is a recombinant virus whose glycoproteins and part of whose 3' nontranslated region (NTR) are derived from a Sindbis-like virus, but the remainder of whose genome is derived from Eastern equine encephalitis (EEE) virus. We show here that Aura virus is a Sindbis-like virus that shares considerable organizational and sequence identity with Sindbis virus. Certain nucleotide sequence elements present in Aura RNA that are believed to function as promoters are almost identical to their Sindbis counterparts, repeated elements in the 3' nontranslated region are shared with Sindbis virus, and important antigenic epitopes are conserved between the two viruses. Despite their close relationship, the two viruses have diverged significantly, sharing 73% amino acid sequence identity in the nonstructural proteins and 62% identity in the structural proteins. This is about the same as the identities between EEE and Venezuelan equine encephalitis virus, whose promoter elements, 3' NTRs, and antigenic epitopes have diverged more radically, such that these two viruses are considered to belong to different subgroups. Importantly, the glycoproteins of WEE are more closely related to those of Sindbis than to those of Aura virus. From this we propose that an ancestral Sindbis-like virus present in the Americas (probably South America) diverged 1000-2000 years ago into a lineage that gave rise to Aura virus and a lineage that gave rise to Sindbis virus and to the Sindbis-like parent of WEE. At some time after this divergence, a Sindbis-like virus belonging to the latter lineage was transferred to the Old World where it gave rise to Sindbis viruses distributed throughout the Old World, and in a separate event a Sindbis-like virus belonging to the same lineage underwent recombination with EEE to give rise to WEE.

Alphavirus↗
PubMed2004

A new Hansenula polymorpha HAP4 homologue which contains only the N-terminal conserved domain of the protein is fully functional in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, the HAP transcriptional complex is involved in the fermentation-respiration shift. This complex is composed of four subunits. Three subunits are necessary for DNA-binding, whereas the Hap4p subunit, glucose-repressed, contains the transcriptional activation domain. Hap4p is the key regulator of the complex activity in response to carbon sources in S. cerevisiae. To date, no HAP4 homologue has been identified, except in Kluyveromyces lactis. Examination of these two HAP4 sequences led to the identification of two very short conserved peptides also identified in other yeasts. In the yeast Hansenula polymorpha, two possible HAP4 homologues have been found. Their deduced amino acid sequences are similar to the ScHap4p and KlHap4p proteins only in the N-terminal 16-amino-acid basic motif. Since molecular genetic tools exist and complete genome sequence is known for this yeast, we expressed one of these putative HpHap4 proteins in S. cerevisiae and showed that this protein is able to restore the growth defect of the S. cerevisiae hap4-deleted strain. A set of experiments was performed to confirm the functional homology of this new gene with ScHAP4. The discovery of a Hap4-regulatory protein in H. polymorpha with only the N-terminal conserved domain of the S. cerevisiae protein indicates that this domain may play a crucial role during evolution.

CCAAT-Binding Factor↗
PubMed1997

Dinucleotide repeat in the 3' flanking region provides a clue to the molecular evolution of the Duffy gene.

The Duffy blood group system consists of three alleles, FYA, FYB, and FY. To study the molecular evolution of the three alleles, we established the polymorphism of a dinucleotide (GT) repeat sequence (designated FyGT/C) in the 3' flanking region of the Duffy gene, and studied the relationship between FyGT/C and Duffy polymorphism in Japanese, people of African origin, and chimpanzee. By single-strand conformation polymorphism and sequence analysis, five and two alleles were identified in Japanese and Africans, respectively. In 110 random Japanese, the FyGT/C genotypes observed were in agreement with Hardy-Weinberg law. From the sequence of the chimpanzee Duffy gene, including both flanking regions, FYB was identified as the ancestral gene of the human alleles. The FyGT/C sequences associated with the FY allele of Africans were distinct from those of Duffy positives, whereas the FYB and FYA alleles shared common FyGT/C sequences. Thus, it is suggested that the first split took place between the FYB and FY alleles, and the second between the FYB and FYA alleles.

Alleles↗
PubMed1990

Nucleotide sequence of Streptomyces fradiae transposable element Tn4556: a class-II transposon related to Tn3.

The first transposable element to be isolated from Streptomyces fradiae, Tn4556, was completely sequenced; the total of 6625 bp have an overall G + C composition of 68%. Computer-aided analysis of this sequence reveals the location of nine open reading frames (ORFs). Several of these ORFs, numbers 1, 2, and 7, contain ribosome-binding sites (RBS) near their putative translation-initiation sites, which share identity with the consensus RBS sequences of Escherichia coli and Bacillus subtilis. ORF1 potentially encodes an 892-amino acid (aa) protein and this deduced aa sequence shares 61% identity with that of the transposase encoded by the tnpA gene of Tn3. Three other ORFs, 2, 3 and 5, potentially encode proteins which are similar in size to the resolvase protein encoded by the Tn3 gene tnpR; however, none of the protein products deduced from these ORF share extensive aa sequence identity with other resolvase proteins.

Amino Acid Sequence↗
PubMed1993

Human L7a ribosomal protein: sequence, structural organization, and expression of a functional gene.

A cDNA coding for the human L7a ribosomal protein (r-protein) was used to isolate the corresponding gene by screening two human genomic libraries constructed in bacteriophage lambda and in a cosmid vector. One of the cosmid clones isolated, cos1.1, contains the whole L7 alpha gene, composed of eight exons and seven introns spanning 3226 bp. As in other mammalian housekeeping genes, the promoter and the first exon of the L7 alpha reside within a CpG-rich island. Furthermore, similar to the other higher eukaryote r-protein-encoding genes characterized so far, the human L7 alpha gene has a C as the major transcriptional start point localized in a pyrimidine-rich region and lacks a canonical TATA sequence. We show that 130 bp of the human L7 alpha gene 5'-flanking region represent the minimal element required to promote its transcription. This element is strikingly conserved between the mouse and human L7 alpha genes. Finally, a comparison of the human L7 alpha gene coding sequence and the predicted amino acid (aa) sequence with the sequences of mouse L7a, rat L7a, and the homologous yeast L4 shows that the aa sequence has been highly conserved during evolution.

Amino Acid Sequence↗
PubMed1994

Transpogenes: the transposition-like integration of short sequence DNA into the yeast 2 micron plasmid creates the STB locus and plasmid-size polymorphism.

The type-2 2 mu plasmid of industrial yeast strains exhibits extensive size polymorphism in the STB (plasmid stability) locus and IR (inverted repeat)-right region. Comparative DNA sequence analyses of STB alleles identified a 38-bp sequence flanked by a 25-bp direct repeat as the underlying structural motif. Variable unequal recombination within the direct repeat accounted for the observed polymorphism of STB alleles. IR-right polymorphism was observed to result from tandem duplication of a 22-bp sequence flanked by a 9-bp direct repeat. The flanking direct repeats marked both loci as originating from the transposition-like integration of short DNA fragments. We call these structures transpogenes and note that these are hybrid structures of host and foreign DNA which can evolve into functional loci.

Base Sequence↗
PubMed2005

A statistical analysis of the TRANSFAC database.

Transcription factors are key regulatory elements that control gene expression. The TRANSFAC database represents the largest repository for experimentally derived transcription factor binding sites (TFBS). Understanding TFBS, which are typically conserved during evolution, helps us identify genomic regions related to human health and disease, and regions that might be predictive of patient outcomes. Here we present a statistical analysis of all TFBS in the TRANSFAC database. Our analysis suggests that current definition of TFBS core regions in TRANSFAC should be re-examined so as to capture a more precise notion of "cores." We offer insight into more appropriate definitions of TFBS consensus sequences and core regions. These revised definitions provide a better understanding of the nature of transcription factor-DNA binding and assist with developing algorithms for de novo TFBS discovery as well as finding novel variants of known TFBS.

Algorithms↗