Block structure and stability of the genetic code

It is known that different codons may be unified into larger groups related to the hierarchical structure, approximate hidden symmetries, and evolutionary origin of the universal genetic code. Using a simplified evolutionary motivated two-letter version of genetic code, the general principles of the most stable coding are discussed. By the complete enumeration in such a reduced code it is strictly proved that the maximum stability with respect to point mutations and shifts in the reading frame needs the fixation of the middle letters within codons in groups with different physico-chemical properties, thus, explaining a key feature of the universal genetic code. The translational stability of the genetic code is studied by the mapping of code onto de Bruijn graph providing both the compact visual representation of mutual relationships between different codons as well as between codons and protein coding DNA sequence and a powerful tool for the investigation of stability of protein coding. Then, the results are extended to four-letter codes. As is shown, the universal genetic code obeys mainly the principles of optimal coding. These results demonstrate the hierarchical character of optimization of universal genetic code with strictly optimal coding being evolved at the earliest stages of molecular evolution. Finally, the universal genetic code is compared with the other natural variants of genetic codes.     

Polymorphism at rDNA loci in barley and its relation with climatic variables

The variation in length of the intergenic spacer (IGS) region of the ribosomal DNA repeat unit was examined in 63 accessions of wild barley, Hordeum spontaneum, and seven accessions of cultivated barley, Hordeum vulgare. The accessions of wild barley were collected from ecologically diverse climatic and edaphic microsites in Israel, and the barley cultivars were those grown in India. Sixteen spacer-length variants (slvs) observed in the present study presumably belonged to two known rDNA loci (Rrn1 and Rrn2). Each accession had one or more variants, which together represented the rDNA phenotype. The rDNA phenotypes of wild barley accessions were widely diverse and differed substantially from those of cultivated barley. The slv phenotypes and the corresponding alleles were shown to be largely correlated with different climatic, edaphic and ecogeographical microsites and niches (the ”Evolution Canyon” at Lower Nahal Oren, Mount Carmel; and Tabigha, Eastern Upper Galilee Mountains), so that a particular rDNA phenotype of an accession could be used to predict the climate and soil to which the accession belonged. This sharp microsite ecogeographic variation in ribosomal DNA appears adaptive in nature, and is presumably driven by climatic and edaphic natural selection. Received: 1 March 2001 / Accepted: 21 May 2001     

Genomics of steroid hormones: in silico analysis of nucleotide sequence variants (polymorphisms) of the enzymes involved in the biosynthesis and metabolism of steroid hormones

Alterations of steroid hormone biosynthesis and metabolism are suspected to be involved in the pathogenesis of several diseases. Several polymorphisms of the enzymes involved in these processes have already been described and some could be associated with certain diseases. We attempted to examine the sequence variants of these genes in order to find novel variants by an in silico analysis. We analyzed the known human nucleotide sequences of the enzymes p450 side-chain cleavage enzyme, steroid 17-alpha-hydroxylase/17,20-lyase, 3-beta-hydroxysteroid dehydrogenase types 1 and 2, 21-hydroxylase, 11-beta-hydroxylase, aldosterone synthase, aromatase, 11-beta-hydroxysteroid dehydrogenase types 1 and 2, steroid 5-alpha-reductase types 1 and 2, steroid 5-beta-reductase, dehydroepiandrosterone sulfotransferase, 17-beta-hydroxysteroid dehydrogenase types 1–3. The analysis was performed using the National Center for Biotechnology Information Database by the search tool blastn. We found numerous sequence variants in both coding and non-coding sequences. The majority of these sequence variants have already been described, nevertheless, some appear as novel variants. Some of these may also have functional significance. We hypothesize over the possible significance of these findings and briefly review the available literature.     

Extensive multiple test centre evaluation of the VecTest malaria antigen panel assay

To determine which species and populations of Anopheles transmit malaria in any given situation, immunological assays for malaria sporozoite antigen can replace traditional microscopical examination of freshly dissected Anopheles. We developed a wicking assay for use with mosquitoes that identifies the presence or absence of specific peptide epitopes of circumsporozoite (CS) protein of Plasmodium falciparum and two strains of Plasmodium vivax (variants 210 and 247). The resulting assay (VecTest Malaria) is a rapid, one-step procedure using a 'dipstick' test strip capable of detecting and distinguishing between P. falciparum and P. vivax infections in mosquitoes. The objective of the present study was to test the efficacy, sensitivity, stability and field-user acceptability of this wicking dipstick assay. In collaboration with 16 test centres world-wide, we evaluated more than 40 000 units of this assay, comparing it to the standard CS ELISA. The 'VecTest Malaria' was found to show 92% sensitivity and 98.1% specificity, with 97.8% accuracy overall. In accelerated storage tests, the dipsticks remained stable for > 15 weeks in dry conditions up to 45 degrees C and in humid conditions up to 37 degrees C. Evidently, this quick and easy dipstick test performs at an acceptable level of reliability and offers practical advantages for field workers needing to make rapid surveys of malaria vectors.     

Molecular cloning, gene localization, and structure of human cyclin B3

Here we describe the molecular cloning of human cyclin B3, its localization, and its structure. It is localized in the subcentromeric region of the X chromosome, still not completely sequenced by the Human Genome Project. This cyclin B3 is unusually large for a mitotic cyclin. Its mRNAs were found in all tissues and were particularly abundant in testis. At least three splice variants were found in the ORF and three variants in the 5'UTR.     

Glycosylated molecular variants of C-reactive proteins from the major carp Catla catla in fresh and polluted aquatic environments

Elevated level of pollutant specific glycosylated molecular variants of C-reactive protein have been purified to electrophoretic homogeneity from the sera of major carp, Catla catla confined in freshwater (CRP_N) and water polluted with nonlethal doses of cadmium (CRP_Cd), mercury (CRP_Hg), phenol (CRP_Ph) and hexachlorocyclohexane (CRP_Hex). These CRPs differ amongst themselves in electrophoretic mobility, and in their carbohydrate content ranging from 20–50%. CRPs interact with pneumococcal C-polysaccharide (CPS) showing different binding constants. Both phosphorylcholine (PC) and calcium are indispensable for binding. Studies on amino acid compositions, electrophoretic analysis, isoelectric focusing, binding to PC & CPS and secondary structures of the purified CRPs indicate, that, they differ from each other. However, they share the common properties of a CRP, including pentraxin structure revealed by electron microscopy. Taken together, our results provide a new structural insight regarding the connection between the presence of unique molecular variants and probably the toxicity therein combated.     

cDNA cloning and expression of the mouse Na/H antiporter (NHE-1) and a potential splice variant

A cDNA for the Mus musculus Na/H exchanger-isoform 1 (NHE-1) was identified in a BALB/c myoblast library by its hybridization to rat NHE-1 sequences. Analysis of the clone showed it to display extensive homology with NHE-1 clones from other mammalian species; however, the region of interspecific homology was abruptly interrupted in the midst of the open reading frame by 166 bp of unrelated sequence. This extra sequence is likely to be an unspliced intron 9. Aside from the retained intron 9, the NHE-1 cDNA clone is otherwise fully processed, with all of the other ten introns removed and containing a poly(A) tract. From PCR results this variant represents a significant but minor population of NHE-1 RNAs. The variant message does associate with polysomes thereby suggesting it to be translated into protein. The location of the retained intron in the carboxy terminus of the protein is such that its translation would produce a protein predicted to be still capable of effecting Na and H translocation but whose regulatory features would be markedly altered.Amino acid sequence comparison of the mouse NHE-1 (derived from the fully processed message) with that of other mammalian species demonstrated two exceptionally divergent regions; the C-terminal cytoplasmic tail (residues 750-790), containing a region of 6-8 contiguous acidic amino acids variably composed of aspartate and glutamate residues, and the N-terminal extracellular domain that includes an N-linked glycosylation site (residues 60-80).     

Human sequence variation and mutation databases

This paper aims to give an overview of current resources onhuman sequence variations and give an idea about the directionin which these services are moving.