Biomedical subjects

G Matassi

Publications and source records attributed to G Matassi.

11 recordsLinked to original sources

PubMed1998

Organization of the human RH50A gene (RHAG) and evolution of base composition of the RH gene family.

Human Rh (rhesus) antigens are expressed in the red cell membrane as a multi-subunit complex, the central core of which is presumably composed of a tetramer made of two Rh and two Rh50 protein subunits. The interaction between Rh and Rh50 polypeptides is thought to be crucial to the correct assembly and transport of the complex to the cell surface. Here, we show that the human RH50A gene (RHAG) is composed of 10 exons whose size and exon/intron junctions are well conserved compared to those of the RH genes. We have also analyzed the RH50A 5' flanking region where the transcription initiation site has been identified. These results conclusively establish that the RH50A and RH genes do belong to the same gene family. Moreover, we show that the RH50A and RH genes are embedded in different compositional genomic contexts (i.e., different isochores) that are likely to drive the evolution of these genes, the base compositions (G + C content) of which differ drastically. Finally, we propose a scenario in which an RH50-like gene is likely to have played a founding role in the evolution of the RH gene family.

Animals↗

PubMed1997

Methylation patterns in the isochores of vertebrate genomes.

5-Methylcytosine (5mC) levels were determined in compositional DNA fractions corresponding to different isochore families from the genomes of Xenopus, chicken, mouse and human, four vertebrates which show different isochore patterns. The results obtained indicate that: (i) positive correlations exist between the 5mC levels and the GC levels of isochores within any given genome; and (ii) DNA from Xenopus isochore families is twice as methylated as DNA from the isochores having the same GC levels from mouse, human and chicken. Moreover, the positive correlations holding between CpG levels and the GC3 levels of coding sequences of warm-blooded vertebrates were shown to comprise two regions with a border at approx. 75% GC3. The correlation corresponding to the higher region (which comprises only very rare high GC3 values in the case of Xenopus) has a higher slope than that corresponding to the lower GC3 values, a phenomenon due in all likelihood, to the increasing contribution of CpG islands. Finally, the observed/expected CpG ratio is higher in Xenopus than in warm-blooded vertebrates.

Animals↗

PubMed1997

Characterization of the recombination hot spot involved in the genomic rearrangement leading to the hybrid D-CE-D gene in the D(VI) phenotype.

In the Caucasian population, the RH locus of RhD-positive individuals is composed of two homologous genes, RHD and RHCE, arranged in tandem but of a single gene, RHCE, in RhD-negative individuals. Many variants recently characterized carry rearranged RH genes, most often by an unidirectional segmental DNA-exchange (gene-conversion) event. In D(VI) variants of type II, RHD is a D-CE-D hybrid gene in which the DNA fragment carrying exons 4-6 has been replaced by the corresponding sequences from the RHCE gene. To identify precisely and characterize the two transition sites, we have studied, by both PCR and sequence analysis, a genomic region between the 3' end of intron 3 and exon 7 in normal RHCE and RHD genes as well as in D(VI) DNA. We show that the D-CE breakpoint is located in intron 3, within a 250-bp fragment comprising an Alu S sequence, and that the CE-D breakpoint lies within a 39-bp fragment in intron 6. This Alu S sequence (and the 100-bp region immediately downstream) most likely defines a recombination hot spot, since there lies also the 5' breakpoint of different rearrangement events leading to D-CE and CE-D transitions in hybrid D(VI),DFR and Dc-,R(N) gene complexes, respectively.

Base Sequence↗

PubMed1996

Molecular characterization of a new urea transporter in the human kidney.

A cDNA clone (HUT2) sharing 61.1% and 89.9% sequence identity with the human erythroid (HUT11) and the rabbit (UT2) urea transporters, respectively, was isolated by homology cloning from a human kidney library. HUT2 transcripts were restricted to the kidney and the HUT2 polypeptide was not immunoprecipitated with blood group Kidd-related antibodies (anti-Jk3) in coupled transcription-translation assays. Functional expression studies in Xenopus oocytes demonstrated that HUT2-mediated urea transport was not inhibited by p-chloromercuribenzene sulfonate (pCMBS) which, however, inhibited the urea flux mediated by HUT11. These findings demonstrate that at least two distinct urea transporters are present in human tissues. By in situ hybridization, the gene encoding HUT2 has been assigned to chromosome 18q12.1-q21-1, as found previously for the Kidd/urea transporter HUT11, suggesting that both genes evolved from duplication of a common ancestor.

Adult↗

PubMed1995

DNA sequence evolution: the sounds of silence.

Silent sites (positions that can undergo synonymous substitutions) in protein-coding genes can illuminate two evolutionary processes. First, despite being silent, they may be subject to natural selection. Among eukaryotes this is exemplified by yeast, where synonymous codon usage patterns are shaped by selection for particular codons that are more efficiently and/or accurately translated by the most abundant tRNAs; codon usage across the genome, and the abundance of different tRNA species, are highly co-adapted. Second, in the absence of selection, silent sites reveal underlying mutational patterns. Codon usage varies enormously among human genes, and yet silent sites do not appear to be influenced by natural selection, suggesting that mutation patterns vary among regions of the genome. At first, the yeast and human genomes were thought to reflect a dichotomy between unicellular and multicellular organisms. However, it now appears that natural selection shapes codon usage in some multicellular species (e.g. Drosophila and Caenorhabditis), and that regional variations in mutation biases occur in yeast. Silent sites (in serine codons) also provide evidence for mutational events changing adjacent nucleotides simultaneously.

Animals↗

PubMed1994

Codon usage and genome evolution.

The rates and patterns of evolution at silent sites in codons reveal much about the basic features of molecular evolution. Recent increases in the amount of sequence data available for various species and more precise knowledge of the chromosomal locations of those sequences, coming in particular from genome projects, reveal that some features of molecular evolution vary around the genome.

Animals↗

PubMed1992

Large-scale methylation patterns in the nuclear genomes of plants.

Methylation was investigated in compositional fractions of nuclear DNA preparations (50-100 kb in size) from five plants (onion, maize, rye, pea and tobacco), and was found to increase from GC-poor to GC-rich fractions. This methylation gradient showed different patterns in different plants and appears, therefore, to represent a novel, characteristic genome feature which concerns the noncoding, intergenic sequences that make up the bulk of the plant genomes investigated and mainly consist of repetitive sequences. The structural and functional implications of these results are discussed.

5-Methylcytosine↗

PubMed1991

Compositional bimodality of the nuclear genome of tobacco.

We have studied the compositional distribution of six genes (or small multigene families) and of one family of transposable elements, Tnt1, in DNA fractions from tobacco (Nicotiana tabacum) separated according to base composition. We have shown that gene distribution is bimodal and that such bimodality is due to the different base composition of the two parental genomes of tobacco (N.sylvestris and N.tomentosiformis) and to the different parental origin of the genes tested. These results indicate a physical separation and an absence of extensive recombination of the parental genomes, which have been together in the tobacco nucleus for a small span of their evolutionary life, and a conservation of their compositional patterns, including gene localization.

Cell Nucleus↗

PubMed1990

Gene distribution and isochore organization in the nuclear genome of plants.

The genomic distribution of 23 nuclear genes from three dicotyledons (pea, sunflower, tobacco) and five monocotyledons of the Gramineae family (barley, maize, rice, oat, wheat) was studied by localizing these genes in DNA fractions obtained by preparative centrifugation in Cs2SO4/BAMD density gradients. Each one of these genes (and of many other related genes and pseudogenes) was found to be located in DNA fragments (50-100 Kb in size) that were less than 1-2% GC apart from each other. This definitively demonstrates the existence of isochores in plant genomes, namely of compositionally homogeneous DNA regions at least 100-200 Kb in size. Moreover, the GC levels of the 23 coding sequences studied, of their first, second and third codon positions, and of the corresponding introns were found to be linearly correlated with the GC levels of the isochores harboring those genes. Compositional correlations displayed increasing slopes when going from second to first to third codon position with obvious effects on codon usage. Coding sequences for seed storage proteins and phytochrome of Gramineae deviate from the compositional correlations just described. Finally, CpG doublets of coding sequences were characterized by a shortage that decreased and vanished with increasing GC levels of the sequences. A number of these findings bear a striking similarity with results previously obtained for vertebrate genes.

Animals↗

PubMed1989

The isochore organization and the compositional distribution of homologous coding sequences in the nuclear genome of plants.

The isochore structure of the nuclear genome of angiosperms described by Salinas et al. (1) was confirmed by using a different experimental approach, namely by showing that the levels of coding sequences from both dicots and Gramineae are linearly correlated with GC levels of the corresponding flanking sequences. The compositional distribution of homologous coding sequences from several orders of dicots and from Gramineae were also studied and shown to mimick the compositional distributions previously seen (1) for coding sequences in general, most coding sequences from Gramineae being much higher than those of the dicots explored. These differences were even stronger for third codon positions and led to striking codon usages for many coding sequences especially in the case of Gramineae.

Cell Nucleus↗

PubMed1988

Compositional compartmentalization and compositional patterns in the nuclear genomes of plants.

We report here results which indicate (i) that the nuclear genomes of angiosperms is characterized by a compositional compartmentalization and an isochore structure; and (ii) that the nuclear genomes of some Gramineae exhibit strikingly different compositional patterns compared to those of many dicots. Indeed, the compositional distribution of nuclear DNA molecules (in the 50-100 Kb size range) from three dicots (pea, sunflower and tobacco) and three monocots (maize, rice and wheat) were found to be centered around lower (41%) and higher (45% for rice, 48% for maize and wheat) GC levels, respectively (and to trail towards even higher GC values in maize and wheat). Experiments on gene localization in density gradient fractions showed a remarkable compositional homogeneity in vast (greater than 100-200 Kb) regions surrounding the genes. On the other hand, the compositional distribution of coding sequences (GenBank and literature data) from dicots (several orders) was found to be narrow, symmetrical and centered around 46% GC, that from monocots (essentially barley, maize and wheat) to be broad, asymmetrical and characterized by an upward trend towards high GC values, with the majority of sequences between 60 and 70% GC. Introns exhibited a similar compositional distribution, but lower GC levels, compared to exons from the same genes.

Cell Nucleus↗