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Biomedical subjects

H Musto

Publications and source records attributed to H Musto.

15 recordsLinked to original sources

Evolutionary genomics of vertebrates and its implications.

The discovery that the vertebrate genomes of warm-blooded vertebrates are mosaics of isochores, long DNA segments homogeneous in base composition, yet belonging to families covering a broad spectrum of GC levels, has led to two major observations. The first is that gene density is strikingly non-uniform in the genome of all vertebrates, gene concentration increasing with increasing GC levels. (Although the genomes of cold-blooded vertebrates are characterized by smaller compositional heterogeneities than those of warm-blooded vertebrates and high GC levels are not attained, their gene distribution is basically similar to that of warm-blooded vertebrates.) The second observation is that the GC-richest and gene-richest isochores underwent a compositional transition (characterized by a strong increase in GC level) between cold- and warm-blooded vertebrates. Evidence to be discussed favors the idea that this compositional transition and the ensuing highly heterogeneous compositional pattern was due to, and was maintained by, natural selection.

Animals

Synonymous codon choices in the extremely GC-poor genome of Plasmodium falciparum: compositional constraints and translational selection.

We have analyzed the patterns of synonymous codon preferences of the nuclear genes of Plasmodium falciparum, a unicellular parasite characterized by an extremely GC-poor genome. When all genes are considered, codon usage is strongly biased toward A and T in third codon positions, as expected, but multivariate statistical analysis detects a major trend among genes. At one end genes display codon choices determined mainly by the extreme genome composition of this parasite, and very probably their expression level is low. At the other end a few genes exhibit an increased relative usage of a particular subset of codons, many of which are C-ending. Since the majority of these few genes is putatively highly expressed, we postulate that the increased C-ending codons are translationally optimal. In conclusion, while codon usage of the majority of P. falciparum genes is determined mainly by compositional constraints, a small number of genes exhibit translational selection.

Animals

Compositional correlations in the chicken genome.

This paper analyses the compositional correlations that hold in the chicken genome. Significant linear correlations were found among the regions studied-coding sequences (and their first, second, and third codon positions), flanking regions (5' and 3'), and introns-as is the case in the human genome. We found that these compositional correlations are not limited to global GC levels but even extend to individual bases. Furthermore, an analysis of 1037 coding sequences has confirmed a correlation among GC(3), GC(2), and GC(1). The implications of these results are discussed.

3' Untranslated Regions

Heterogeneity in codon usage in the flatworm Schistosoma mansoni.

Synonymous codon choices vary considerably among Schistosoma mansoni genes. Principal components analysis detects a single major trend among genes, which highly correlates with GC content in third codon positions and exons, but does not discriminate among putatively highly and lowly expressed genes. The effective number of codons used in each gene, and its distribution when plotted against GC3, suggests that codon usage is shaped mainly by mutational biases. The GC content of exons, GC3, 5', 3', and flanking (5' + 3' + introns) regions are all correlated among them, suggesting that variations in GC content may exist among different regions of the S. mansoni genome. We propose that this genome structure might be among the most important factors shaping codon usage in this species, although the action of selection on certain sequences cannot be excluded.

Animals

The analysis of protein coding genes suggests monophyly of Trypanosoma.

We analyze evolutionary relationships among members of the family Trypanosomatidae, with particular emphasis on whether protein coding genes support paraphyly of the genus Trypanosoma. Phylogenetic reconstruction based on three different protein coding genes (glyceraldehyde-3-phosphate dehydrogenase, trypanothione reductase, and alpha-tubulin) suggests that Trypanosoma is monophyletic. Moreover, pairwise comparisons of other protein coding genes show that the distances between Trypanosoma cruzi and T. brucei are significantly smaller than are the distances between each Trypanosoma species and Crithidia or Leishmania. These results contradict recent published phylogenies based on nuclear rRNA genes which suggested that T. cruzi is more closely related to Leishmania and Crithidia than to T. brucei.

Animals

Cytogenetic and molecular analysis of the satellite DNA of the genus Ctenomys (Rodentia Octodontidae) from Uruguay.

The genus of subterranean rodents Ctenomys presents the widest range of variability in diploid number among mammals (from 2n = 10 to 2n = 70). In Uruguay, this variability is observed in karyotypes with 2n = 44, 50 or 58 and two geographically isolated populations with 70 chromosomes but different karyotypic structure. The last three populations were analyzed in the present study. They present a satellite DNA, which was isolated from genomic DNA after AluI digestion. In situ hybridization showed that this satellite DNA is located in the centromeric region of a few chromosomes, coincident with Hoechst 33258 staining and C-banding patterns. A similar satellite DNA was detected in Argentinian species of this genus. We established that, in spite of differences in number of positive heterochromatic blocks per karyotype, the C value is the same in the three populations studied. The nature and possible evolutionary path of this repeated DNA is discussed.

Animals

Compositional properties of nuclear genes from Plasmodium falciparum.

We have analyzed the compositional distributions of coding sequences and their different codon positions, as well as the codon usage of the nuclear genes of Plasmodium falciparum, a parasite characterized by an extremely GC-poor genome. As expected, coding sequences are AT-rich, codon usage is strongly biased towards A or T in third codon positions, and some particular amino acids (aa) are especially abundant in the encoded proteins. Remarkably, however, no difference was detected between housekeeping (HK) and antigen (Ag) genes, in spite of differences in expression level and evolutionary constraints. Moreover, all the features found in P. falciparum are very similar to those found in a bacterium characterized by a very GC-poor genome, Staphylococcus aureus. These findings stress the importance of compositional constraints in determining codon usage and aa utilisation.

Amino Acids

Compositional correlations in the nuclear genes of the flatworm Schistosoma mansoni.

We have investigated the genome organization in the flatworm Schistosoma mansoni. First, we analyzed the compositional distributions of the three codon positions. Second, we investigated the correlations that exist between (1) the GC levels of exons against flanking regions, (2) the GC levels of third codon positions against flanking regions, (3) the dinucleotide frequencies of exons against flanking regions, and (4) the GC levels of 5' against 3' regions. The modality of the distribution of third codon positions, together with the significant correlations found, leads us to propose that the nuclear genome of this species is compositionally compartmentalized.

Animals

The compositional compartments of the nuclear genomes of Trypanosoma brucei and T. cruzi.

Fractionation of DNA from Trypanosoma brucei and T. equiperdum by centrifugation in a Cs2SO4/BAMD density gradient indicated that these genomes are compositionally compartmentalized, a conclusion confirmed by the analysis of the compositional distribution of third codon positions from T. brucei and T. cruzi. In order to investigate whether this compartmentalization is accompanied by the often different properties of coding sequences, we have analyzed and compared the compositional compartments with respect to dinucleotide frequency and amino-acid usage of the encoded proteins of all gene sequences available in the GenBank database from T. brucei and T. cruzi. In all cases, the compartments displayed remarkable differences. These results are similar to findings obtained in highly compartmentalized genomes, like those of warm-blooded vertebrates.

Amino Acids

The nuclear genomes of African and American trypanosomes are strikingly different.

We have investigated the compositional distributions of exons and their different codon positions, as well as the codon usage and amino-acid (aa) composition of the nuclear genomes of the African and American trypanosomes Trypanosoma brucei and T. cruzi. Very large differences between the two species were found in all the properties investigated. The most striking differences concern the compositional distributions of third codon positions and the extremely large nucleotide divergence of third codon position for homologous genes encoding proteins that are highly conserved in their aa sequences. Moreover, if coding sequences from each species are divided into two groups according to the GC levels in third codon positions, very different codon usages and aa compositions are found. This indicates a compositional compartmentalization in both genomes which had previously been detected in T. brucei (and T. equiperdum) by compositional fractionation.

Animals

Possible implications of CpG avoidance in the flatworm Schistosoma mansoni.

We report the analysis of the biases of CpG, TpG, and CpA of all the DNA sequences data from the Trematode Schistosoma mansoni. Our results show CpG avoidance whereas TpG and CpA frequencies are over the expected values. These characteristics are similar to the biases displayed by methylated genomes, but in platyhelminths 5mC has not been detected by biochemical methods. The possible implications of this CpG shortage are discussed.

Animals

Dinucleotide biases in the platyhelminth Schistosoma mansoni.

The analysis of dinucleotide biases in coding and flanking regions, introns, rDNA and repetitive sequences, in the flatworm Schistosoma mansoni is reported. Except for rDNA, all regions display CpG avoidance and TpG plus CpA excess, which might be evidence of the presence of 5mC. The distribution and hierarchies of dinucleotides differ from the data published for invertebrate and vertebrate coding sequences.

Animals

Comparative DNA analysis of three South American marsupials.

Published information on marsupials DNA is limited to a group of species belonging to only one genus. No previous reports have been written on South American species. In this paper we characterize the DNA of three out of the four marsupials found in Uruguay. Analytical and preparative ultracentrifugations in neutral CsCl gradients, including four intercalating agents and in Cs2SO4 gradients in presence of increasing amounts of Hg++ ion did not allow us to separate any satellite fraction. The buoyant density of the unique peak measured in CsCl gradients was in every case 1.697 g/cc with a G-C content of 37.7%. Digestion of total DNA with 11 restriction endonucleases produced a different pattern of bands for the three species, although some possible homologies could be established. Hybridization with 32P-rRNA of Southern blots of the gels containing digested DNAs demonstrated that the repeated sequences evidenced do not correspond to the ribosomal cistrons.

Animals

Compositional constraints in the extremely GC-poor genome of Plasmodium falciparum.

We have analyzed the compositional properties of coding (protein encoding) and non-coding sequences of Plasmodium falciparum, a unicellular parasite characterized by an extremely AT-rich genome. GC% levels, base and dinucleotide frequencies were studied. We found that among the various factors that contribute to the properties of the sequences analyzed, the most relevant are the compositional constraints which operate on the whole genome.

Animals