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At least 757 records · Page 42Linked to original sources
PubMed2006

Evolution of cis elements in the differential expression of two Hoxa2 coparalogous genes in pufferfish (Takifugu rubripes).

Sequence divergence in cis-regulatory elements is an important mechanism contributing to functional diversity of genes during evolution. Gene duplication and divergence provide an opportunity for selectively preserving initial functions and evolving new activities. Many vertebrates have 39 Hox genes organized into four clusters (Hoxa-Hoxd); however, some ray-finned fishes have extra Hox clusters. There is a single Hoxa2 gene in most vertebrates, whereas fugu (Takifugu rubripes) and medaka (Oryzias latipes) have two coparalogous genes [Hoxa2(a) and Hoxa2(b)]. In the hindbrain, both genes are expressed in rhombomere (r) 2, but only Hoxa2(b) is expressed in r3, r4, and r5. Multiple regulatory modules directing segmental expression of chicken and mouse Hoxa2 genes have been identified, and each module is composed of a series of discrete elements. We used these modules to investigate the basis of differential expression of duplicated Hoxa2 genes, as a model for understanding the divergence of cis-regulatory elements. Therefore, we cloned putative regulatory regions of the fugu and medaka Hoxa2(a) and -(b) genes and assayed their activity. We found that these modules direct reporter expression in a chicken assay, in a manner corresponding to their endogenous expression pattern in fugu. Although sequence comparisons reveal many differences between the two coparalogous genes, specific subtle changes in seven cis elements of the Hoxa2(a) gene restore segmental regulatory activity. Therefore, drift in subsets of the elements in the regulatory modules is responsible for the differential expression of the two coparalogous genes, thus providing insight into the evolution of cis elements.

Animals↗
PubMed1987

Novel type of plasmid-borne resistance to trimethoprim.

A novel trait for transferable resistance to high concentrations of trimethoprim was found to dominate among enterobacteria collected from different parts of Sri Lanka. Drug resistance was a result of the production of dihydrofolate reductase with a decreased sensitivity to antifolates. By characterization of the partially purified enzyme and by restriction enzyme digestion analysis, the newly found gene was shown to be distinct from the earlier known plasmid-borne resistance genes which express dihydrofolate reductases of types I, II, and III. Cloning of fragments containing the resistance gene and further restriction enzyme digestion analysis showed that this gene was inserted very close to a sulfonamide resistance gene. Evolution of trimethoprim resistance in Sri Lanka thus seems to have taken a different route from that taken in the industrialized world, where transposon Tn7 seems to dominate. The close combination of the new trimethoprim resistance gene with sulfonamide resistance on the plasmids studied would effect an efficient spread of these genes, since trimethoprim has most often been used in combination with a sulfonamide.

Chromatography, Ion Exchange↗
PubMed2006

Tempo and mode of early gene loss in endosymbiotic bacteria from insects.

BACKGROUND: Understanding evolutionary processes that drive genome reduction requires determining the tempo (rate) and the mode (size and types of deletions) of gene losses. In this study, we analysed five endosymbiotic genome sequences of the gamma-proteobacteria (three different Buchnera aphidicola strains, Wigglesworthia glossinidia, Blochmannia floridanus) to test if gene loss could be driven by the selective importance of genes. We used a parsimony method to reconstruct a minimal ancestral genome of insect endosymbionts and quantified gene loss along the branches of the phylogenetic tree. To evaluate the selective or functional importance of genes, we used a parameter that measures the level of adaptive codon bias in E. coli (i.e. codon adaptive index, or CAI), and also estimates of evolutionary rates (Ka) between pairs of orthologs either in free-living bacteria or in pairs of symbionts. RESULTS: Our results demonstrate that genes lost in the early stages of symbiosis were on average less selectively constrained than genes conserved in any of the extant symbiotic strains studied. These results also extend to more recent events of gene losses (i.e. among Buchnera strains) that still tend to concentrate on genes with low adaptive bias in E. coli and high evolutionary rates both in free-living and in symbiotic lineages. In addition, we analyzed the physical organization of gene losses for early steps of symbiosis acquisition under the hypothesis of a common origin of different symbioses. In contrast with previous findings we show that gene losses mostly occurred through loss of rather small blocks and mostly in syntenic regions between at least one of the symbionts and present-day E. coli. CONCLUSION: At both ancient and recent stages of symbiosis evolution, gene loss was at least partially influenced by selection, highly conserved genes being retained more readily than lowly conserved genes: although losses might result from drift due to the bottlenecking of endosymbiontic populations, we demonstrated that purifying selection also acted by retaining genes of greater selective importance.

Animals↗
PubMed1995

Investigating hypothetical products from noncoding frames (HyPNoFs).

Hypothetical Products from Noncoding Frames (i.e., HyPNoFs) are hypothetical, not-coded proteins, translated from alternate reading frames (i.e., coding + 1 and coding + 2) of cDNAs. HyPNoFs of CD4, PKC, oncostatin, bcl-2 proto-oncogene, tumor suppressor p53, cystic fibrosis transmembrane regulator (CFTR), and tumor necrosis factors alpha and beta were searched as query sequences vs the SWISS-PROT data bank. Homology searchers carried out revealed that hypothetical products (i.e., HyPNoFs) may share high similarity with real protein products actually coded. Sequence similarity of hypothetical products to real proteins is sometimes very high, suggesting common conformational features, according to the Sander and Schneider cutoff value. This finding supports the hypothesis that eukaryotic DNA, currently considered to be monocistronic, might occasionally have polycistronic regions, carrying different protein messages on overlapping frames. As yet, polycistronic genes have been observed in viral genomes only. The presence of polycistronic regions in eukaryotic genes is likely reminiscent of an ancient strategy, rather than a present feature of the genome in eukaryotes. These data suggest that thorough investigation of HyPNoFs is likely to improve our ability to trace genes' evolution and to investigate structure-function relationships of protein and DNA sequences.

Amino Acid Sequence↗
PubMed2003

PaTre: a method for paralogy trees construction.

Genomes can be described as a collection of clusters, the gene families, whose members are called paralogs. Paralogs are genes that most probably share duplication history and show a significant similarity in their sequences, even if they perform slightly different biological function. Among the different mechanisms that have led to an increase of the genomic information during biological evolution, gene duplication is probably the most important. To better understand duplication events, the first step is to investigate the history of the gene families in order to detect which duplication events have taken place, and in which relative (partial) order. Here we present a method, called PaTre, that, given a gene family, attempts to construct the paralogy tree of the family. We will work under the hypothesis that every family member derives from a duplication process of another member. By the term paralogy tree, we mean a directed tree in which the root represents the most ancient paralog of the family and each oriented arc (a, b) represents the existence of a duplication event from the template gene a to its copy b. Notice that gene a survives the event and can serve as a template of more than one duplication event; in fact, there can be more than one arc leaving a. PaTre uses new algorithmic techniques motivated by the specific application at hand. The reliability of the inferential process has been tested by means of a simulator that implements different hypotheses on the duplication-with-modification paradigm and on three examples of different biological gene families, belonging either to lower and higher organisms.

Arabidopsis↗
PubMed2006

The ABC of the BX-C: the bithorax complex explained.

As one of two Drosophila Hox clusters, the bithorax complex (BX-C) is responsible for determining the posterior thorax and each abdominal segment of the fly. Through the dissection of its large cis-regulatory region, biologists have obtained a wealth of knowledge that has informed our understanding of gene expression, chromatin dynamics and gene evolution. This primer attempts to distill and explain our current knowledge about this classic, complex locus.

Animals↗
PubMed2004

Accelerated rates of intron gain/loss and protein evolution in duplicate genes in human and mouse malaria parasites.

Very little is known about molecular evolution in the human malaria parasite Plasmodium falciparum. Given the potentially important role that introns play in directing transcription and the posttranscriptional control of gene expression, we compare rates of intron/gain loss and intronic substitution in P. falciparum and the rodent malaria P. y. yoelii in both orthologous and duplicate genes. Specifically, we test the hypothesis that intron gain/loss and protein evolution is accelerated in duplicate genes versus orthologous genes in both parasites using the genome sequence of both species. We find that duplicate genes in both P. falciparum and P. y. yoelii exhibit a dramatic acceleration of both intron gain/loss and protein evolution in comparison with orthologs, suggesting increased directional and/or relaxed selection in duplicate genes. Further, we find that rates of intron gain/loss and protein evolution are weakly coupled in orthologs but not paralogs, supporting the hypothesis that selection acts on genes as functionally integrated units after speciation but not necessarily after gene duplication. In contrast, we find that rates of nucleotide substitution do not differ significantly between intronic sites and synonymous sites among duplicate genes, implying that a large fraction of intronic sites in Plasmodium evolve under little or no selective constraint.

Animals↗
PubMed1996

Testis-specific expression of mRNAs for a unique human type 1 hexokinase lacking the porin-binding domain.

Several enzymes in the glycolytic pathway are reported to have spermatogenic cell-specific isozymes. We reported recently the cloning of cDNAs representing three unique type 1 hexokinase mRNAs (mHk1-sa, mHk1-sb, and mHk1-sc) present only in mouse spermatogenic cells and the patterns of expression of these mRNAs (Mori et al., 1993: Biol Reprod 49:191-203). The mRNAs contain a spermatogenic cell-specific sequence, but lack the sequence for the porin-binding domain that somatic cell hexokinases use to bind to a pore-forming protein in the outer mitochondrial membrane. We now report the cloning of cDNAs representing three unique human type 1 hexokinase mRNAs (hHK1-ta, hHK1-tb, and hHK1-tc) expressed in testis, but not detected by Northern analysis in other human tissues. These mRNAs also contain a testis-specific sequence not present in somatic cell type 1 hexokinase, but lack the sequence for the porin-binding domain. The hHK1-tb and hHK1-tc mRNAs each contain an additional unique sequence. The testis-specific sequence of the human mRNAs is similar to the spermatogenic cell-specific sequence of the mouse mRNAs. Furthermore, Northern analysis of RNA from mouse, hamster, guinea pig, rabbit, ram, human, and rat demonstrated expression of type 1 hexokinase mRNAs lacking the porin-binding domain in the testes of these mammals. These results suggest that hexokinase may have unique structural or functional features in spermatogenic cells and support a model proposed by others for hexokinase gene evolution in mammals.

Amino Acid Sequence↗
PubMed2004

Conserved function of medaka pink-eyed dilution in melanin synthesis and its divergent transcriptional regulation in gonads among vertebrates.

Medaka is emerging as a model organism for the study of vertebrate development and genetics, and its effectiveness in forward genetics should prove equal to that of zebrafish. Here, we identify by positional cloning a gene responsible for the medaka i-3 albino mutant. i-3 larvae have weakly tyrosinase-positive cells but lack strongly positive and dendritic cells, suggesting loss of fully differentiated melanophores. The region surrounding the i-3 locus is syntenic to human 19p13, but a BAC clone covering the i-3 locus contained orthologs located at 15q11-13, including OCA2 (P). Medaka P consists of 842 amino acids and shares approximately 65% identity with mammalian P proteins. The i-3 mutation is a four-base deletion in exon 13, which causes a frameshift and truncation of the protein. We detected medaka P transcripts in melanin-producing eyeballs and (putative) skin melanophores on embryos and an alternatively spliced form in the non-melanin-producing ovary or oocytes. The mouse p is similarly expressed in gonads, but not alternatively spliced. This is the first isolation of nonmammalian P, the functional mechanism of action of which has not yet been elucidated, even in mammals. Further investigation of the functions of P proteins and the regulation of their expression will provide new insight into body color determination and gene evolution.

Amino Acid Sequence↗
PubMed1992

Human erythroid 5-aminolevulinate synthase. Gene structure and species-specific differences in alternative RNA splicing.

Erythroid 5-aminolevulinate synthase (ALAS) is expressed exclusively in differentiating erythroid cells as the principal isoform of the enzyme to catalyze the first step of the heme biosynthetic pathway. The human gene encoding this isozyme was isolated from a cosmid library, and its structure was characterized with restriction mapping followed by sequencing of fragments. The gene is 22 kilobases long and has 11 exons. Exon 2 encodes the N-terminal signal sequence required for mitochondrial import, exons 3 and 4 encode a variable portion of the N-terminal end, and exons 5-11 the highly conserved C-terminal portion of the mature protein, respectively. Enzymatic amplification of human reticulocyte RNA using PCR techniques revealed two erythroid ALAS mRNA transcripts predicted to encode both the prototypical 64-kDa isoform as well as a novel smaller isoform with a deletion of 37 amino acids near the N terminus. The two mRNA isoforms are generated by alternative splicing of exon 4 and are expressed in fetal erythroid cells as well as at all stages of erythroid development tested, so that there is no evidence of differentiation-specific regulation of exon 4 splicing. However, striking species-specific differences were observed in that alternative splicing of exon 4 was found in man but not dog or mouse; also, the previously described alternative splicing within exon 3 in mouse was not observed in man. This transcript heterogeneity suggests the existence of erythroid ALAS protein isoforms with potentially distinct functional or regulatory roles. The occurrence of species-specific splicing in the least conserved region of the enzyme may reflect another mechanism of gene evolution in eukaryotes.

5-Aminolevulinate Synthetase↗
PubMed1989

Interferons as gene activators. Indications for repeated gene duplication during the evolution of a cluster of interferon-activatable genes on murine chromosome 1.

We have described earlier a gene cluster, including at least six interferon-activatable genes closely linked to the erythroid alpha spectrin locus and the serum amyloid P-component locus on murine chromosome 1. Here, we report that sequences of three genes from the cluster (the 201, 202, and 204 genes) are very similar in a segment extending from at least 550 nucleotides upstream of the 3' end of the transcription initiation region to beyond the first exon intron border (96% similarity between the 202 and 204 genes and 89% similarity between the 201 and 204 genes). This region contains the following two types of interferon-responsive enhancers: a GA box and a Friedman Stark sequence. The proteins coded for by the 202 gene (51 kDa) and the 204 gene (72 kDa) are hydrophilic. The amino acids have been conserved in the two proteins in 47% of the sequence. Each protein includes two apparently contiguous, approximately 200-amino acid long segments with much sequence similarity (27% in the 202 protein and 34% in the 204 protein). These segments are preceded in the 204 protein only by a segment including four perfect and three imperfect repeats of a 7 amino acid sequence. These and other data suggest that the evolution of the gene cluster involved the duplication of a DNA segment generating a double length transcription unit and subsequent divergence and duplication of this unit giving rise to at least two interferon-activatable genes (the 202 and 204 genes).

Amino Acid Sequence↗
PubMed2001

The human complement C9 gene: structural analysis of the 5' gene region and genetic polymorphism studies.

C9 is the last of the human complement components creating the membrane attack complex. The single chain serum protein is encoded by a gene located on chromosome 5p13 that is composed of 11 exons. With the aid of inverse PCR, the hitherto unknown regions flanking exon 1 and the 3' part of exon 11 (3'UTR) have been sequenced. A computer-based analysis of the 300-bp region located just upstream of the AUG start codon showed homologies to known DNA modules which affect the transcriptional regulation of certain genes. The most striking of these is a sequence that may substitute the missing TATA box in initiating C9 transcription. In the 3'UTR, three successive polyadenylation signals were found. Although the C9 protein is invariant, four different single nucleotide polymorphisms (SNPs) have been observed at the DNA level by exon-specific PCR and direct sequencing. None of them changes the amino acid composition of the mature protein. Due to a C --> T transition in exon 1 at cDNA position 17, the fifth amino acid of the leader peptide may be either an arginine or a tryptophane. Using either PCR/ RFLP analysis (exons 1 and 11) or allele-specific PCR (intron 1 and exon 4), each polymorphism can be characterized without sequencing. All of the exon 1, intron 1 and exon 11 variants could be detected in small population samples of European, Thai or South American Indian origin. In contrast, the exon 4 C variant was observed only once in a European. The first three SNPs can be combined to designate eight different 'C9 alleles'. Of these, six have actually be found. These data provide strong evidence that several mutation and recombination events occurred in the course of C9 gene evolution.

3' Untranslated Regions↗
PubMed2005

Origin, evolution and genetic effects of nuclear insertions of organelle DNA.

In eukaryotes, nuclear genomes are subject to an influx of DNA from mitochondria and plastids. The nuclear insertion of organellar sequences can occur during the illegitimate repair of double-stranded breaks. After integration, nuclear organelle DNA is modified by point mutations, and by deletions. Insertion of organelle DNA into nuclear genes is not rare and can potentially have harmful effects. In humans, some insertions of nuclear mitochondrial DNA are associated with heritable diseases. It remains to be determined whether nuclear organelle DNA can contribute beneficially to gene evolution.

Cell Nucleus↗
PubMed2003

[Origin of SARS from accelerated evolution of a virus by combined pollution].

The SARS virus origin which obviously differs from the theory of out-space origin and the theory of wildlife origin was theoretically discussed based on principles of pollution-evolution ecology, pathogenesis and infectant characteristics of SARS, and some relevant experimental evidence. It emphasizes on the fact that increasingly combined pollution in China provides a substantial basis for virus evolution. Gene recombination and fusion of more than one virus in ecosystems should take charge with the origin of a SARS virus. In particular, a common cold or influenza virus can acceleratedly changed into a superpower common cold or influenza virus through genetic mutation and gene recombination by increasingly combined pollution. This work can be useful for human beings to overcome SARS in theory.

Animals↗
PubMed2005

Asymmetric evolution of duplicate genes encoding the CCAAT-binding factor NF-Y in plant genomes.

NF-Y is a ubiquitous CCAAT-binding factor composed of NF-YA, NF-YB and NF-YC. Multiple genes encoding NF-Y subunits have been identified in plant genomes. It remains unclear whether the duplicate genes underwent different evolutionary patterns. Likelihood-ratio tests were used to examine whether the amino acid substitution rates are the same between duplicate genes. The influences of selection on evolution were evaluated by comparing the conservative and radical amino acid substitution rates, as well as maximum-likelihood analysis. Some NF-YB and NF-YC duplicates showed significant evidence of asymmetric evolution but not the NF-YA duplicates. Most amino acid replacements in the NF-YB and NF-YC duplicates result in changes in hydropathy, polar requirement and polarity. The physicochemical changes in the sequences of NF-YB seem to be coupled to asymmetric divergence in gene function. Plant NF-Y genes have evolved in different patterns. Relaxed selective constraints following gene duplication are most likely responsible for the unequal evolutionary rates and distinct divergence patterns of duplicate NF-Y genes. Positive selection may have promoted amino acid hydropathy changes in the NF-YC duplicates.

Amino Acid Substitution↗
PubMed2005

Evidence for host-driven selection of the HIV type 1 vpr gene in vivo during HIV disease progression in a transfusion-acquired cohort.

An epidemiologically linked HIV-1-infected cohort, in which a nonprogressor donor infected two recipients who progressed to AIDS, was examined. Sequence analysis, over time, of HIV-1 vpr gene quasispecies from uncultured peripheral blood cells revealed an insertion of arginine at position 90 altering a highly conserved C-terminal motif, believed to play a role in Vpr nuclear targeting. Full genome analysis from each patient showed no gene defects in other gene regions, implying that the mutational selection was unique to the vpr gene. A detailed analysis of the vpr quasispecies showed very little amino acid diversity in the nonprogressing donor, whereas, following viral transmission, the amino acid diversity increased dramatically over time in tandem with disease progression in the two recipients. Although the R insertion at position 90 was present in all three individuals, the variable degree of additional amino acid changes over time may have influenced HIV disease in the nonprogressor donor and the two progressing recipients. These data provide the first evidence in favor of vpr gene evolution over time, which was host-driven. The status of the nonprogressing donor was consistent with a highly protective B-57 HLA type, which was absent in the two progressing recipients, implying a role for host HLA type and other immunologic selective pressures in vpr gene selection in vivo.

Acquired Immunodeficiency Syndrome↗
PubMed1988

The rat alpha-tropomyosin gene generates a minimum of six different mRNAs coding for striated, smooth, and nonmuscle isoforms by alternative splicing.

Tropomyosin (TM), a ubiquitous protein, is a component of the contractile apparatus of all cells. In nonmuscle cells, it is found in stress fibers, while in sarcomeric and nonsarcomeric muscle, it is a component of the thin filament. Several different TM isoforms specific for nonmuscle cells and different types of muscle cell have been described. As for other contractile proteins, it was assumed that smooth, striated, and nonmuscle isoforms were each encoded by different sets of genes. Through the use of S1 nuclease mapping, RNA blots, and 5' extension analyses, we showed that the rat alpha-TM gene, whose expression was until now considered to be restricted to muscle cells, generates many different tissue-specific isoforms. The promoter of the gene appears to be very similar to other housekeeping promoters in both its pattern of utilization, being active in most cell types, and its lack of any canonical sequence elements. The rat alpha-TM gene is split into at least 13 exons, 7 of which are alternatively spliced in a tissue-specific manner. This gene arrangement, which also includes two different 3' ends, generates a minimum of six different mRNAs each with the capacity to code for a different protein. These distinct TM isoforms are expressed specifically in nonmuscle and smooth and striated (cardiac and skeletal) muscle cells. The tissue-specific expression and developmental regulation of these isoforms is, therefore, produced by alternative mRNA processing. Moreover, structural and sequence comparisons among TM genes from different phyla suggest that alternative splicing is evolutionarily a very old event that played an important role in gene evolution and might have appeared concomitantly with or even before constitutive splicing.

Amino Acid Sequence↗