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PubMed1981

The bacteriorhodopsin gene.

The bacteriorhodopsin gene has been identified in a 5.3-kilobase restriction endonuclease fragment isolated from Halobacterium halobium DNA, using a cloned cDNA fragment as the probe. Of the 1229 nucleotides whose sequence was determined in the genomic fragment, 786 correspond to the structural gene of bacteriorhodopsin, 360 are upstream from the initiator methionine codon, and 83 are downstream from the COOH terminus. The bacteriorhodopsin gene codes for a precursor sequence of 13 amino acids at the NH2 terminus, 248 amino acids that are present in the mature protein and an additional aspartic acid at the COOH terminus. This determination of the DNA sequence for an archaebacterial gene reveals that the standard genetic code is used; however, there is a marked preference for either G or C in the third codon position. The gene does not contain any intervening sequences and no prokaryotic promoter can be identified in the region immediately upstream from the structural gene. The bacteriorhodopsin mRNA contains at the 5' terminus only three nucleotides beyond the initiating AUG codon and this terminus can form a hairpin structure. Immediately downstream from this structure there is a sequence complementary to the 3' terminus of H. halobium 16S rRNA.

Amino Acid Sequence↗
PubMed1999

Opportunities at the interface of chemistry and biology.

The combination of the tools and principles of chemistry, together with the tools of modern molecular biology, allow us to create complex synthetic and natural molecules, and processes with novel biological, chemical and physical properties. This article illustrates the tremendous opportunity that lies at this interface of chemistry and biology by describing a number of examples, ranging from efforts to expand the genetic code of living organisms to the use of combinatorial methods to generate biologically active synthetic molecules.

Antibodies, Catalytic↗
PubMed1999

Partial sequence of a sponge mitochondrial genome reveals sequence similarity to Cnidaria in cytochrome oxidase subunit II and the large ribosomal RNA subunit.

A 2550-bp portion of the mitochondrial genome of a Demosponge, genus Tetilla, was amplified from whole genomic DNA extract and sequenced. The sequence was found to code for the 3' end of the 16S rRNA gene, cytochrome c oxidase subunit II, a lysine tRNA, ATPase subunit 8, and a 5' portion of ATPase subunit 6. The Porifera cluster distinctly within the eumetazoan radiation, as a sister group to the Cnidaria. Also, the mitochondrial genetic code of this sponge is likely identical to that found in the Cnidaria. Both the full COII DNA and protein sequences and a portion of the 16S rRNA gene were found to possess a striking similarity to published Cnidarian mtDNA sequences, allying the Porifera more closely to the Cnidaria than to any other metazoan phylum. The gene arrangement, COII-tRNALys-ATP8-ATP6, is observed in many Eumetazoan phyla and is apparently ancestral in the metazoa.

Amino Acid Sequence↗
PubMed2005

Complete nucleotide sequence of the mitochondrial DNA from Kluyveromyces lactis.

The total nucleotide sequence of the mitochondrial genome of the yeast Kluyveromyces lactis was determined. The DNA is a circular molecule of 40,291 base pairs, with 26.1% GC. It contains a set of protein- and RNA-coding genes equivalent to those of the Saccharomyces cerevisiae mitochondrial genome. The genome size is about one half of that of S. cerevisiae mitochondrial DNA. The difference in size is due essentially to a reduced proportion of intergenic and intronic sequences. The coding sequences occupy about one third of the genome, the rest being composed of AT-rich sequences and numerous short GC-rich clusters that are dispersed mostly in the non-coding regions and a few within coding sequences. The presence of these GC clusters is a characteristic feature common to K. lactis and S. cerevisiae mitochondrial DNA, although their sequence patterns are different. The absence of the NADH dehydrogenase subunit genes distinguishes this yeast and S. cerevisiae from the typically aerobic species. The genetic code appears to be that of the standard fungal mitochondrial genomes, with UGA as a tryptophan codon. There are only 22 transfer RNA genes, those corresponding to CUN and CGN codons being missing. CUN codons are absent in the protein-coding sequences. There are five CGN codons within the open reading frames, but they are located exclusively in the introns, rendering them untranslatable. Introns are found only the genes in KlCOX1 and LrRNA. The transcription promoter motif known in S. cerevisiae and several other yeast species is also present. All genes are transcribed from the same strand, except those on a single 7-kilobase pairs segment (EMBL Accession No. AY654900).

Base Sequence↗
PubMed2001

[Genetic counseling versus genetic self testing: what challenges?].

The development of molecular genetics allows us to have access to an increasing number of informations on our own genetic code. This leads to a new form of medical activity, called predictive and preclinical medicine. It involves significant ethical stakes in terms of individual information and consent for the test as well as in terms of support for the patient which is summarized by the concept of "genetic council". The self-test, which bypasses this medical supervision, represents, for the patient becoming a consumer, a threat from the emotional point of view as well as from a social perspective (insurance, access to the working market). This analysis shows that the only real driving force for the development of the genetic self-test is commercial. To resist what is sometimes called "genetic shopping" one must consider an ethical, deontological and social priority.

Ethics, Medical↗
PubMed1988

Genes encoding a subunit of respiratory NADH dehydrogenase (ND1) and a reverse transcriptase-like protein (RTL) are linked to ribosomal RNA gene pieces in Chlamydomonas reinhardtii mitochondrial DNA.

Two long and uninterrupted reading frames, specifying the ND1 and RTL genes, are embedded within fragmented rRNA genes in the 15.8-kb mitochondrial genome of Chlamydomonas reinhardtii, a unicellular green alga. The ND1 gene encodes a subunit of respiratory NADH dehydrogenase, a standard mitochondrial gene, while the RTL gene is related to the reverse transcriptase-like part of some optional introns and plasmids in fungal mitochondria. The universal genetic code is used in both the ND1 and RTL genes; however, the latter is distinguished from the other protein coding genes of C. reinhardtii mtDNA by several characteristics which suggest that RTL may be a more recently acquired gene. Flanking each of the protein coding genes, whose mRNAs are of similar abundance, are some of the 'scrambled' rRNA gene pieces that are a unique feature of C. reinhardtii mtDNA. These sub-genic modules give rise to high-abundance, small-sized pieces of rRNA, which are not spliced in this genetic system. Judging by the observed juxtaposition of transcripts as they hybridize to the genome, the mature rRNA and mRNA species from this region appear to be generated by precise endonucleolytic cleavages of a long RNA precursor. We suggest a model, involving reverse transcription of rRNAs and insertion of the resulting cDNAs into the mitochondrial genome, that might account for the pattern of dispersed rRNA gene pieces in C. reinhardtii mitochondrial DNA.

Amino Acid Sequence↗
PubMed1995

Nucleotide sequence and gene organization of the starfish Asterina pectinifera mitochondrial genome.

The 16,260-bp mitochondrial DNA (mtDNA) from the starfish Asterina pectinifera has been sequenced. The genes for 13 proteins, two rRNAs and 22 tRNAs are organized in an extremely economical fashion, similar to those of other animal mtDNAs, with some of the genes overlapping each other. The gene organization is the same as that for another echinoderm, sea urchin, except for the inversion of a 4.6-kb segment that contains genes for two proteins, 13 tRNAs and the 16S rRNA. Judging from the organization of the protein coding genes, mammalian mtDNAs resemble the sea urchin mtDNA more than that of the starfish. The region around the 3' end of the 12S rRNA gene of the starfish shows a high similarity with those for vertebrates. This region encodes a possible stem and loop structure; similar potential structures occur in this region of vertebrate mtDNAs and also in nonmitochondrial small subunit rRNA. A similar stem and loop structure is also found at the 3' end of the 16S rRNA genes in A. pectinifera, in another starfish Pisaster ochraceus, in vertebrates and in Drosophila, but not in sea urchins. The full sequence data confirm the presumption that AGA/AGG, AUA and AAA codons, respectively, code for serine, isoleucine, and asparagine in the starfish mitochondria, and that AGA/AGG codons are read by tRNA(GCUSer), which possesses a truncated dihydrouridine arm, that was previously suggested from a partial mtDNA sequence. The structural characteristics of tRNAs and possible mechanisms for the change in the mitochondrial genetic code are also discussed.

Amino Acid Sequence↗
PubMedDate not supplied

Genetic and environmental influences on type A behavior pattern: evidence from twins and their parents in the Netherlands Twin Register.

OBJECTIVE: There is a dose-response positive relationship between type A behavior (TABP) and cardiovascular disease-related symptoms. Estimates of heritability for TABP from previous studies vary; this might be explained by limitations in the sizes and compositions of the samples. METHODS: This study combines a large sample size, twin and parental, data from males and females, two generations of young adults and older adults, and the use of structural equation modeling (SEM) and full information maximum likelihood (FIML) estimation. To assess TABP, the Jenkins Activity Survey (JAS) was collected from MZ and DZ twins and their parents (n = 1670 twin families). Structural equation modeling is used to evaluate and estimate the effects of additive and nonadditive genetic effects, nonshared environmental effects, and competitive sibling interaction. RESULTS: Forty-five percent of the variance in TABP was the result of genetic factors (28% were additive and 17% were nonadditive). The remaining 55% of the variance was explained by environmental factors not shared by the members of the same family. Competitive sibling interaction effects were not significant. There was no evidence of sex differences either in variances or means. CONCLUSION: Understanding the sources of variance on TABP is important for therapy and prevention. According to the present results, the relevant environmental factors for the development of TABP are not shared by the members of the same family. The genetic portion of the variance is also worth considering for therapeutic purposes. Although the genetic code cannot be altered, its effects on behavior may be modifiable through the treatment of the biological mediators.

Adolescent↗
PubMed1984

The Drosophila mitochondrial genome.

The mitochondrial genome of Drosophila yakuba is a circular DNA molecule of 16019 nucleotide pairs. The sequence contains the genes for two rRNA molecules, 22 tRNA molecules, five known polypeptides (cytochrome b, cytochrome c oxidase subunits I, II, III and ATPase subunit 6) and eight unidentified polypeptides (URF1, 2, 3, 4L, 4, 5, 6 and A6L). Between the tRNA(ile) and small rRNA genes there occurs a sequence of 1077 nucleotides that is 92.8 per cent A + T and lacks reading frames greater than 123 nucleotides. Replication of the molecule originates in this A + T-rich region and proceeds toward the small rRNA gene. Non-coding nucleotides between genes are either absent or occur in low numbers (1 to 31). A sequence equivalent in size and secondary structure potential to the sequence associated with the initiation of second strand synthesis in mammalian mtDNA is missing in Drosophila mtDNA. While the genes found in D. yakuba and mammalian mtDNAs are the same, the relative arrangement of many of these genes differs considerably in the two molecules. The proportions of the two strands of the D. yakuba molecule which serve as template for transcription of genes are approximately equal. This contrasts with the situation in mammalian mtDNAs where all genes except those for URF6 and eight tRNAs are transcribed from one strand. The dihydrouridine and T psi C loops of D. yakuba mt-tRNA genes are highly variable in size, and among these genes there is a general deficiency of nucleotides which are highly conserved in prokaryotic and eukaryotic nuclear-coded tRNAs. The D. yakuba tRNA(AGYser) gene is unusual in that an eleven nucleotide loop replaces the dihydrouridine arm. D. yakuba mitochondrial polypeptide genes utilize 59 sense codons. However, 93.8 per cent of all codons used end in A or T. Unique variations occur in the Drosophila mitochondrial genetic code. AGA appears to specify serine rather than arginine as in the standard code, or termination as in the mammalian mitochondrial code. The Drosophila COI gene lacks a standard translation initiation codon, and may utilize a four nucleotide codon ATAA for that purpose. As in other metazoan mitochondria, TGA and ATA specify tryptophan and methionine, respectively. As a tRNA with an anticodon (TCT) specific for AGA codons does not appear to be encoded in D. yakuba mtDNA, it seems likely that the GCU anticodon of the D. yakuba tRNA which recognizes AGY (serine) codons can also recognize AGA.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Genetics of methyl-accepting chemotaxis proteins in Escherichia coli: organization of the tar region.

The tar locus of Escherichia coli specifies one of the major species of methyl-accepting proteins involved in the chemotactic behavior of this organism. The physical and genetic organization of the tar region was investigated with a series of specialized lambda transducing phages and plasmid clones. The tar gene was mapped at the promoter-proximal end of an operon containing five other chemotaxis-related loci. Four of those genes (cheR, cheB, cheY and cheZ) are required for all chemotactic responses; consequently, polar mutations in the tar gene resulted in a generally nonchemotactic phenotype. The fifth gene, tap, was mapped between the tar and cheR loci and specified the production of a 65-kilodalton methyl-accepting protein. Unlike the tar locus, which is required for chemotaxis to aspartate and maltose, mutants lacking only the tap function had no obvious defects in chemotactic ability. Genetic and physical maps of the tar-tap region were constructed with Mu d1 (Apr lac) insertion mutations, whose polar properties conferred a phenotype suitable for deletion mapping studies. Restriction endonuclease analyses of phage and plasmid clones indicated that all of the genetic coding capacity in the tar region is now accounted for.

Bacterial Proteins↗
PubMed2006

Application of heuristic optimization techniques and algorithm tuning to multilayered sorptive barrier design.

Although heuristic optimization techniques are increasingly applied in environmental engineering applications, algorithm selection and configuration are often approached in an ad hoc fashion. In this study, the design of a multilayer sorptive barrier system served as a benchmark problem for evaluating several algorithm-tuning procedures, as applied to three global optimization techniques (genetic algorithms, simulated annealing, and particle swarm optimization). Each design problem was configured as a combinatorial optimization in which sorptive materials were selected for inclusion in a landfill liner to minimize the transport of three common organic contaminants. Relative to multilayer sorptive barrier design, study results indicate (i) the binary-coded genetic algorithm is highly efficient and requires minimal tuning, (ii) constraint violations must be carefully integrated to avoid poor algorithm convergence, and (iii) search algorithm performance is strongly influenced by the physical-chemical properties of the organic contaminants of concern. More generally, the results suggest that formal algorithm tuning, which has not been widely applied to environmental engineering optimization, can significantly improve algorithm performance and provide insight into the physical processes that control environmental systems.

Algorithms↗
PubMed1986

The development of the small intestine.

The remarkable degree of coordination between the development of various aspects of gastrointestinal function suggests that the process may be triggered by a single or a few central mechanisms, such as weaning and (or) hormones. Precocious development of enzyme and transport function can be induced by exogenous thyroxine and corticosteroids, while thyroidectomy and adrenalectomy abolish the normal pattern of postnatal development. These hormones may have a primary or a permissive role. Activation of the dormant hormonal mechanism could be controlled by a genetically coded biologic clock, such as chronologic age, or by a biological signal such as body size and oral intake. Generally speaking, shortly after birth, there are increases in the intestinal mucosal surface area, brush border membrane enzymes, and carrier-mediated transport. These adaptive changes occur as a result of the genetic endowment of the animal, but may be modified by environmental factors, particularly nutrient intake.

Aging↗
PubMed2001

Complete DNA sequence and gene organization of the mitochondrial genome of the liverfluke, Fasciola hepatica L. (Platyhelminthes; Trematoda).

The complete nucleotide sequence of the mitochondrial (mt) DNA molecule of the liverfluke, Fasciola hepatica (phylum Platyhelminthes, class Trematoda, family Fasciolidae), was determined. It comprises 14462 bp, contains 12 protein-encoding, 2 ribosomal and 22 transfer RNA genes, and is the second complete flatworm (and the first trematode) mitochondrial sequence to be described in detail. All of the genes are transcribed from the same strand. Of the genes typically found in mitochondrial genomes of eumetazoans, only atp8 is absent. The nad4L and nad4 genes overlap by 40 nt. Most intergenic sequences are very short. Two larger non-coding regions are present. The longer one (817 nt) is located between trnG and cox3 and consists of 8 identical tandem repeats of 85 nt, rich in G and C, followed by 1 imperfect repeat. The shorter non-coding region (187 nt) exhibits no special features and is separated from the longer region by trnG. The gene arrangement resembles that of some other trematodes including the eastern Asian Schistosoma species (and cyclophyllidean cestode species) but it is strikingly different from that of the African schistosomes, represented by Schistosoma mansoni. The genetic code is as inferred previously for flatworms. Transfer RNA genes range in length from 58 to 70 nt, their products producing characteristic 'clover leaf' structures, except for tRNA(S(UNC)) and tRNA(S(AGN)) lacking the DHU arm.

Animals↗
PubMed2003

Reduced folate carrier: biochemistry and molecular biology of the normal and methotrexate-resistant cell.

The cytotoxic drug methotrexate uses the reduced folate carrier for transport into the cell, where it inhibits key enzymes in nucleotide biosynthesis. Resistance to methotrexate can be achieved by altering the genetic code of the reduced folate carrier gene and thus change the structure and function of the protein. Our understanding of RFC structure and function is based on the information gained from studying the uptake of folates and antifolates in living cells and the application of molecular techniques to determine gene expression and genetic mutations. The aim of this essay is to explain the structure and function of the reduced folate carrier, review the molecular biology of the reduced folate carrier gene and the mutations and polymorphisms that can result in methotrexate resistance.

Amino Acid Sequence↗
PubMed1987

Genetic variation between woodchuck populations with high and low prevalence rates of woodchuck hepatitis virus infection.

Woodchuck hepatitis virus (WHV) infection is known to be endemic in areas of the mid-Atlantic states but is apparently absent from populations in New York and much of New England. Blood samples of 40 woodchucks (Marmota monax) from New York and from Delaware were examined by starch gel electrophoresis, and 18 monomorphic and six polymorphic protein-coding genetic systems were identified. Mendelian inheritance of variants of the six polymorphic systems was confirmed in 52 laboratory offspring of the original samples. Average heterozygosity of 0.066 in New York woodchucks and 0.039 in Delaware woodchucks were high values for mammals, although similar to those of other sciurids. Significant heterogeneity between samples from New York and Delaware woodchucks was observed at two loci (peptidase with glycyl leucine-4 and phosphogluconate dehydrogenase), suggesting that these populations were genetically distinct. Whether there are genetically determined differences in response to WHV infection remains to be determined experimentally.

Alleles↗
PubMed1995

Genetic dissection of inflammatory responses.

Recent advances in classical genetics, molecular biology, and genomics herald a renaissance of genetic analysis of hereditary disease in both humans and animal models. It is increasingly feasible to analyze multifactorial traits both genetically and functionally. These advances parallel research aimed at unravelling the genetic code of humans and model species. Only the integration of these two approaches will secure the functionally significant conclusion of the genomic exercise.

Animals↗
PubMed2005

Why genes persist in organelle genomes.

Mitochondria and plastids (including chloroplasts) have a small but vital genetic coding capacity, but what are the properties of some genes that dictate that they must remain encoded in organelles?

Chloroplasts↗
PubMed1994

Rates of transition and transversion in coding sequences since the human-rodent divergence.

Protein-coding sequences of 337 human genes were compared with those of homologous genes from rodent (mouse or rat). A composite alignment containing 477,189 nucleotide positions was constructed, and 21,570 amino acid replacements were inferred. The rates of transitional and transversional silent substitutions in fourfold degenerate sites are estimated as 1.71 x 10(-9) and 1.22 x 10(-9) site -1 year -1, respectively. Rates of substitutions in replacement sites, subject to selective constraints mediated by the genetic code, are lower, but also reflect a transitional bias. The amino acid exchange rejected least often during evolution is Asp/Glu, which is fixed at 30% the rate of transversions in silent sites. The most mutable amino acids in this survey are threonine and serine; serine coded by AGY is more mutable than serine coded by TCN. A scoring matrix for evaluating amino acid similarity was derived from this study.

Amino Acid Sequence↗