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Biomedical subjects

P Liò

Publications and source records attributed to P Liò.

9 recordsLinked to original sources

Paralogous histidine biosynthetic genes: evolutionary analysis of the Saccharomyces cerevisiae HIS6 and HIS7 genes.

The HIS6 gene from Saccharomyces cerevisiae strain YNN282 is able to complement both the S. cerevisiae his6 and the Escherichia coli hisA mutations. The cloning and the nucleotide sequence indicated that this gene encodes a putative phosphoribosyl-5-amino-1-phosphoribosyl-4-imidazolecarboxiamide isomerase (5' Pro-FAR isomerase, EC 5.3.1.16) of 261 amino acids, with a molecular weight of 29,554. The HIS6 gene product shares a significant degree of sequence similarity with the prokaryotic HisA proteins and HisF proteins, and with the C-terminal domain of the S. cerevisiae HIS7 protein (homologous to HisF), indicating that the yeast HIS6 and HIS7 genes are paralogous. Moreover, the HIS6 gene is organized into two homologous modules half the size of the entire gene, typical of all the known prokaryotic hisA and hisF genes. The structure of the yeast HIS6 gene supports the two-step evolutionary model suggested by Fani et al. (J. Mol. Evol. 1994; 38: 489-495) to explain the present-day hisA and hisF genes. According to this idea, the hisF gene originated from the duplication of an ancestral hisA gene which, in turn, was the result of an earlier gene elongation event involving an ancestral module half the size of the extant gene. Results reported in this paper also suggest that these two successive paralogous gene duplications took probably place in the early steps of molecular evolution of the histidine pathway, well before the diversification of the three domains, and that this pathway was one of the metabolic activities of the last common ancestor. The molecular evolution of the yeast HIS6 and HIS7 genes is also discussed.

Aldose-Ketose Isomerases

Comparison of parametric and nonparametric methods to map oligogenes by linkage.

A sample of 95 sib pairs affected with insulin-dependent diabetes and typed with their normal parents for 28 markers on chromosome 6 has been analyzed by several methods. When appropriate parameters are efficiently estimated, a parametric model is equivalent to the beta model, which is superior to nonparametric alternatives both in single point tests (as found previously) and in multipoint tests. Theory is given for meta-analysis combined with allelic association, and problems that may be associated with errors of map location and/or marker typing are identified. Reducing by multipoint analysis the number of association tests in a dense map can give a 3-fold reduction in the critical lod, and therefore in the cost of positional cloning.

Adult

A physiological and molecular analysis of the genus Nicotiana.

An analysis of the evolution of the genus Nicotiana was carried out with physiological and molecular tools. The capacity of explants from seedlings of several species of Nicotiana to differentiate roots or shoots or to habituate was used to ascertain whether the in vitro behavior of species has a nonrandom distribution in the genus. The results obtained allowed us to identify two groups of species, one root-forming prone composed of Paniculatae (subgenus Rustica) and the other composed of Alatae, Repandae, and Noctiflorae (subgenus Petunioides), with a major tendency toward the production of shoots. Habituation capacity was characteristic of species randomly distributed throughout the phylogenetic tree. These data suggest fixation throughout the evolution of coadapted gene complexes (hormone-related genes) involved in the control of developmental processes. RAPDs, on the other hand, used as molecular markers for the clustering of related species, seem entirely coherent both with classical morphological and karyological studies and with in vitro physiological methods, supporting an early subdivision of the whole genus into two diverging developmental patterns.

Adaptation, Physiological

Analysis of genomic patchiness of Haemophilus influenzae and Saccharomyces cerevisiae chromosomes.

We have analysed some aspects of the primary structure of the chromosome of the prokaryote Haemophilus influenzae and of the eukaryote Saccharomyces cerevisiae that share the same G + C content. In particular, we have investigated genomic patchiness over the gene size level (10 Kb) and that patchiness due to long homogenous tracts. Long polypurine and polypyrmidine tracts that are largely over-represented in S. cerevisiae chromosomes and under-represented in H. influenzae, are responsible for a large fraction of long correlation signals. Generating mechanisms of long homogenous tracts are DNA replication slippage and duplication events that appear to be linked processes driving chromosome primary structure evolution.

Base Sequence

High statistics block entropy measures of DNA sequences.

We have used an improved block-entropy measure in order to gain some further insights into the short-range correlations present in whole chromosomes of S. cerevisiae, viruses and organelles and very large genomic regions of E. coli. Although DNA sequences are largely inhomogeneous and word frequencies are unevenly distributed, the comparison of entire chromosomes and large genomic regions show a "bulk" composition homogeneity. This property suggests that biases in selection, directional mutational pressure and recombination processes act in homogenizing the base composition of the DNA molecules within a genome but their mode of action, relative impact and direction may vary in different organisms. The most interesting results appear to be the differences between the SW (C,G/A,T) and RY (A,G/C,T) two-letter alphabet entropies. Deviations from randomness in E. coli and S. cerevisiae sequences particularly concern SW dinucleotide frequencies and RY tetranucleotide frequencies.

Base Sequence

Selection, mutations and codon usage in a bacterial model.

We present a statistical model of bacterial evolution based on the coupling between codon usage and tRNA abundance. Such a model interprets this aspect of the evolutionary process as a balance between the codon homogenization effect due to mutation process and the improvement of the translation phase due to natural selection. We develop a thermodynamical description of the asymptotic state of the model. The analysis of naturally occurring sequences shows that the effect of natural selection on codon bias affects genes whose products are largely required at maximal growth rate conditions or undergo rapid transient increases.

Bacteria

Molecular evolution of the histidine biosynthetic pathway.

The available sequences of genes encoding the enzymes associated with histidine biosynthesis suggest that this is an ancient metabolic pathway that was assembled prior to the diversification of the Bacteria, Archaea, and Eucarya. Paralogous duplications, gene elongation, and fusion events involving different his genes have played a major role in shaping this biosynthetic route. Evidence that the hisA and the hisF genes and their homologous are the result of two successive duplication events that apparently took place before the separation of the three cellular lineages is extended. These two successive gene duplication events as well as the homology between the hisH genes and the sequences encoding the TrpG-type amidotransferases support the idea that during the early stages of metabolic evolution at least parts of the histidine biosynthetic pathway were mediated by enzymes of broader substrate specificities. Maximum likelihood trees calculated for the available sequences of genes encoding these enzymes have been obtained. Their topologies support the possibility of an evolutionary proximity of archaebacteria with low GC Gram-positive bacteria. This observation is consistent with those detected by other workers using the sequences of heat-shock proteins (HSP70), glutamine synthetases, glutamate dehydrogenases, and carbamoylphosphate synthetases.

Aldose-Ketose Isomerases

The evolution of the histidine biosynthetic genes in prokaryotes: a common ancestor for the hisA and hisF genes.

The hisA and hisF genes belong to the histidine operon that has been extensively studied in the enterobacteria Escherichia coli and Salmonella typhimurium where the hisA gene codes for the phosphoribosyl-5-amino-1-phosphoribosyl-4-imidazolecarboxamide isomerase (EC 5.3.1.16) catalyzing the fourth step of the histidine biosynthetic pathway, and the hisF gene codes for a cyclase catalyzing the sixth reaction. Comparative analysis of nucleotide and predicted amino acid sequence of hisA and hisF genes in different microorganisms showed extensive sequence homology (43% considering similar amino acids), suggesting that the two genes arose from an ancestral gene by duplication and subsequent evolutionary divergence. A more detailed analysis, including mutual information, revealed an internal duplication both in hisA and hisF genes in each of the considered microorganisms. We propose that the hisA and hisF have originated from the duplication of a smaller ancestral gene corresponding to half the size of the actual genes followed by rapid evolutionary divergence. The involvement of gene elongation, gene duplication, and gene fusion in the evolution of the histidine biosynthetic genes is also discussed.

Aldose-Ketose Isomerases