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Istituto Veneto di Scienze, Lettere ed Arti - Testata per la stampa

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Giorgio Bernardi

Giorgio Bernardi

Directeur de Recherche Honoraire du CNRS (Centre Nationale de la Recherche Scientifique)
Presidente dell'IUBS (International Union of Biological Sciences) 

- s.c.n.r. 30 giugno 2004, s.c.s. 1 settembre 2009. 
Laureato in Medicina a Padova nel 1952 e in Fisica a Strasburgo nel 1967, il Dr. Bernardi dopo uno stage Post-Dottorato in Canada, ha svolto una carriera di ricercatore presso il CNRS (Centre National de Recherche Scientifique). In particolare dal 1959 al 1969 presso il Centro di Ricerca sulle Macromolecole di Strasburgo e dal 1970 al 1998 presso il l'Istituto Jacques Monod di Parigi di cui è stato Direttore e Capo del Laboratorio di Genetica Molecolare. 
Dal 1998 è Presidente della Stazione Zoologica Anton Dohrn di Napoli e Capo del Laboratorio di Evoluzione Molecolare.
Durante la sua lunga carriera scientifica il Dr. Bernardi ha conseguito numerosi riconoscimenti internazionali quali, ad esempio, le Lauree "honoris causa" conferitegli dall'Istituto Engelhardt di Mosca e dall'Università di Ancona.
Attualmente il Dr. Bernardi è Presidente dell'ISME (International Society of Molecular Evolution) e del Consiglio Scientifico dell'Ufficio UNESCO di Venezia. Il Dr. Bernardi è inoltre membro di numerose Società Scientifiche Nazionali ed Internazionali ed è Editore in Capo della rivista scientifica GENE.
Dal 1959 le ricerche del Dr. Bernardi sono centrate sull'organizzazione e l'evoluzione del genoma, con speciale interesse per quanto riguarda l'interazione genoma/ambiente. Un libro appena pubblicato ("Structural and evolutionary genomics: natural selection in genome evolution"; Elsevier, 2004) sintetizza le ricerche del laboratorio e presenta la nuova teoria "neo-selezionista" dell'evoluzione del genoma.Degrees:
1952: M.D. (cum laude), University of Padova, Italy. Thesis on the determination of phosphate esters in animal tissues (work started in 1951 in the Biochemistry Department of the Nobel Institute, Karolinska Institutet, Stockholm, Sweden; Director Prof. Hugo Theorell).
1953-56: Examinations in Physics, University of Pavia, Italy. 
1962: "Libero Docente" in Physical Biochemistry, Rome, Italy.
1967: Doctorat d'Etat ès-Sciences Physiques, University of Strasbourg, France (Chairman of the Jury : Jacques Monod).Appointments:
1953-56 Assistant, Department of Biochemistry, Universities of Padova and Pavia, Italy. 
1956-57 Research Fellow, Centre de Recherches sur les Macromolécules, Strasbourg, France and Institute of Advanced Technology, Bradford, England.
1957-59 Post-Doctoral Research Fellow, National Research Council, Ottawa, Canada. 
1959-62 Chargé de Recherches, CNRS.
1962-68 Maître de Recherche, CNRS. 
1968-73 Directeur de Recherche, CNRS. 
1973-97 Directeur de Recherche de Classe Exceptionnelle, CNRS.
1997-2002 Directeur de Recherche Emerite, CNRS.
2002- Directeur de Recherche Honoraire, CNRS 
1959-69 Centre de Recherches sur les Macromolécules, Strasbourg, France. 
1970-2003 Head of Laboratoire de Génétique Moléculaire, Institut Jacques Monod, Paris, France.
1978-81 Co-Director of the Institut de Recherche en Biologie Moléculaire (later, Institut Jacques Monod), Paris. 
1997-2002 Expert, Consiglio Nazionale delle Ricerche (CNR), Rome, Italy. 
1998- President of Stazione Zoologica Anton Dohrn, Naples Italy and Head of the Laboratory of Molecular Evolution.

1962 Visiting Scientist, Department of Biophysics, Johns Hopkins University, Baltimore, Md., USA (Prof. C.A. Thomas, Jr.). 
1981-84 Fogarty Scholar, Fogarty International Center, National Institutes of Health, Bethesda, Md., USA (Dr. G. Felsenfeld; Dr. M. Singer) (Summers). 
1995 Visiting Professor, University of Osaka, Institute for Molecular & Cellular Biology, Osaka, Japan (Prof. K. Matsubara) (July-September). 
1996-97 Visiting Professor, National Institute of Genetics Mishima, Japan (Prof. T. Gojobori) (July-August). 
1999 Scholar of the European Union Senior Research Program in Japan, National Institute of Genetics, Mishima, Japan (Prof. T. Gojobori) (July-August).Honors:
1966 Member of the European Molecular Biology Organization (EMBO).
1973 1st Karl-August-Forster Prize, Akademie der Wissenschaften und der Literatur, Mainz, Germany. 
1977 Honorary Member of the Società Italiana di Biologia Sperimentale. 
1981 Listed as one of the 1,000 most cited authors (Institute for Scientific Information, Philadelphia, PA., USA; survey of 1965-1978 publications). 
1982 ICSU/TWAS/UNESCO Lecturer, University of Costa Rica, San José, Costa Rica (August).
1986 Diplôme d'honneur of the Federation of the European Biochemical Societies (FEBS). 
1989- Member of Academia Europea. 
1994 1st Engelhardt Lecture, Moscow. 
1997- Member of the "Società Nazionale di Scienze, Lettere e Arti", Naples (Italy). 
1997 1st Bayev Lecture, Moscow, Russia; 
1997 "Doctor honoris causa", Engelhardt Institute of Molecular Biology, Moscow, Russia.
1998 EMBO Lecture, Montesilvano, Italy
2001 "Erasmus Lecture", Academia Europea, Venice, Italy
2003 "Doctor honoris causa", University of Ancona, ItalyOffices Held:
1977-86 Course Committee of FEBS (Federation of European Biochemical Societies). 
1980- Standing Advisory Committee on Recombinant DNA of EMBO. 
1981-86 Interest Group on Genome and Structure Expression of IUB (International Union of Biochemistry). 
1982-96 Committee for Genetic Experimentation (COGENE) of the International Council of Scientific Unions (ICSU). 
1993- International Society of Molecular Evolution.
2001-04 International Union of Biological Sciences (IUBS) (Secretary General).
2002- Scientific Council of UNESCO Regional Bureau for Science for Europe (ROSTE-Venice).Member 
1974-78 Course Committee of EMBO. 
1975-80 Scientific Council of the Stazione Zoologica (Naples). 
1988-95 Scientific Council of the Stazione Zoologica (Naples).
1975-82 Committee of Biological Chemistry of CNRS. 
1976-81 Committee for Genetic Experimentation, EMBO. 
1976-81 Committee for Genetic Experimentation (COGENE) of the International Council of Scientific Unions (ICSU). 
1982-86 Scientific Council of the Institute of Molecular & Cellular Pathology (Bruxelles).
1989- Committee on the Human Genome, UNESCO. 
1991- Scientific Council of the Institute of Molecular Medical Sciences, 460 Page Mill Road, Palo Alto, California (USA). 
1994- Scientific Council of Engelhardt Institute of Molecular Biology (Moscow). 
1997- Scientific Council, Centro di Endocrinologia e Cancerologia Sperimentale (Naples).
1998- Scientific Council of Istituto di Biotecnologie Mediche Avanzate (Milan). 
1999- Scientific Council of the Station de Biologie Marine de Concarneau.
2001-02: Scientific Council of UNESCO Regional Bureau for Science for Europe (ROSTE-Venice).
2001- Advisory Committee of AIST Bioinformatics Research Consortium, Tokyo, Japan.
2002 Selection Committee for the International Prize for Biology, Tokyo, Japan.
2002 Committee for the Craaford Prize, Stockholm, Sweden. 
2004 Committee for the Rey Jaime I Prize, Valencia, Spain.Major Research Lines
Prof. Giorgio BernardiChromatography of nucleic acids on hydroxyapatite.
The development of this methodology (Bernardi, 1965) led to the separation of single and double stranded DNA, so opening the door to the study of the reassociation kinetics of DNA and the discovery of repeated sequences in eukaryotic genomes. It could be shown that in the case of both nucleic acids and proteins, separations were based on the fact that native structures had more binding groups on their surfaces compared to denatured structures (see Bernardi, 1971, for a review article).Acid deoxyribonuclease
First purified in Bernardi's Laboratory, acid DNase was the first enzyme shown to be endowed with a specificity towards DNA sequences. A dimeric, allosteric enzyme, cutting both DNA strands at the same time, acid DNase was a prefiguration of restriction enzymes (purified ten years later) and was used to demonstrate sequence differences among different DNAs, such as yeast mitochondrial DNA, satellite DNAs, and compositional DNA fractions from mammalian genomes. This work was summed up in three review articles (Bernardi, 1968, 1971; Bernardi et al., 1973).The mitochondrial genome of yeast. 
Bernardi and coworkers provided the first demonstration that the cytoplasmic "petite colonie" mutation of yeast (Ephrussi, 1949) was due to large deletions in the mitochondrial genome (see Bernardi, 1979, for a review). The major discoveries on this model genome were the demonstrations of (i) abundant intergenic sequences (made up of long AT spacers and short GC clusters), which were responsible for the excisions leading to the defective mitochondrial genomes of "petite" mutants; (ii) physical recombination in the mitochondrial genome; (iii) the effect of flanking non-coding sequences on the replicative efficiency of ori sequences; (iv) the effect of temperature on the replicative efficiency of ori sequence in petite mutants, in which a crucial stem-and-loop structure was only made of AT base pairs; this provided the first evidence for reversible transconformations of a genome by an environmental factor, temperature (Goursot et al., 1988); (v) the fact that the replication efficiency of petite genomes explains the outcome of crosses with wild-type cells (the phenomenon of suppressivity): the more efficient the replication of the petite mutant entering the cross, the higher the number of petite mutants in the progeny.
The nuclear genome of warm-blooded vertebrates. 
The major discoveries in this field were (i) the demonstration of a striking compositional heterogeneity in the genomes of warm-blooded vertebrates, which could be described as mosaics of isochores (long, relatively homogeneous regions belonging to a small number of families); (ii) the demonstration that, in contrast, cold-blooded vertebrates were endowed with genomes characterized by a much less striking heterogeneity, so raising the problem of a compositional transition between the genomes of cold-and warm-blooded vertebrates; (iii) the existence of strong compositional correlations between coding and flanking non-coding sequences as well as between different codon positions, the latter being a universal correlation valid from prokaryotes to human; (iv) the demonstration that gene distribution was strikingly non-uniform in the vertebrate genome, about 50% of the genes being located in the 10-15% of the genome characterized by an open chromatin structures, and a weakly or strongly higher GC level (in cold- and warm-blooded vertebrates, respectively); (v) the distribution of isochores and genes in human and mouse chromosomes and in interphase nuclei; the results obtained in the nuclei showed an extremely decondensed chromatin structure for the GC-rich, gene-rich regions of the genome, and a very compact chromatin structure for the GC-poor, gene-poor regions. The investigations on the nuclear genome of vertebrates have been reviewed by Bernardi (1985, 1989, 1995, 2000 a,b).The integration of retroviral sequences in the mammalian genomes. 
Starting in 1979, a series on investigations led to the demonstration that stably integrated, transcribed proviral sequences were localized in isochores matching their base composition. In other words, stability of integration and transcription was associated with a localization in the mammalian genome that mimicked that of host genes (a review article is Rynditch et al., 1998). Viral sequences integrated in compositionally non-matching regions were rare and not transcribed. These findings showed the effect of the composition of flanking non-coding sequences on the expression of integrated viral sequences. As mentioned above, similar effects on transcription and replication were found in the mitochondrial genome of yeast. These results obviously go against the idea of non-coding sequences being junk DNA.The genomes of other eukaryotes and prokaryotes. 
The key conclusions of these investigations (covering the genomes of plants, insects, unicellular eukaryotes and prokaryotes) were (i) that a genome compartmentalization is not at all restricted to vertebrates, being quite widespread among eukaryotes; (ii) that, at least in a number of cases, the compositional compartmentalization was the result of regional GC increases associated with temperature (see the following section); and (iii) that, in the case of Gramineae, genes were concentrated in regions (collectively called the gene space) encompassing a very narrow GC range; this is due to an invasion of transposons in the gene-rich regions of the genome; the narrow GC range is determined by the abundant transposons flanking the genes.
Molecular evolution. 
The major discoveries made on the vertebrate genome, the compositional compartmentalization into a mosaic of isochores, the genome phenotypes (the different compsitional patterns e.g. of cold- and warm-blooded vertebrates), the genomic code (the compositional correlations between coding and non-coding sequences, as well as between the codon positions), the bimodal gene distribution and its correlation with functional properties, could not be accounted for by the neutral theory of Kimura. This raised two problems. The first one was how to explain the formation and maintenance of the mosaic isochore organization of warm-blooded vertebrates. The explanation provided was that natural selection (more precisely, negative or purifying selection) was responsible for both phenomena. The advantage of increasing the stability of the gene-dense regions of the genome by increasing their GC level could be due to the increased body temperature following the appearance of homeothermy. Several lines of evidence on both vertebrate and prokaryotic genomes have very recently confirmed this explanation. 
The second problem was to reconcile natural selection with the overwhelming numbers of neutral or nearly neutral mutations. This problem was solved by proposing a regional selection mechanism in which the average composition of an isochore must be kept within certain thresholds in order to avoid a deleterious effect on the expression of genes embedded in that isochore. This model of genome evolution, the neo-selectionist model, inspired by the results obtained on the expression of integrated viral sequences (see above), only requires negative selection on the average composition of a region.Summing up
During a research career spanning more than 50 years, Dr. Bernardi's work has been centered since 1959 on two major areas, molecular genetics and molecular evolution, in which he has played a major role. His detailed analysis of the organization of the eukaryotic genome and, in particular, of the vertebrate genome has led him to investigate genome evolution from an original point of view.
While the basic results have been outlined above, it is relevant to stress the general interest of these discoveries. Indeed, the results obtained on the organization of the vertebrate genome could not be accounted by any mechanism essentially based on stochastic changes, like the fixation of mutations by random drift proposed by the neutral theory. Yet, the results are compatible with the neutral theory, provided that natural selection operates not only on single-nucleotide changes (as it is the case in coding sequences) but also at a regional level in the non-coding sequences that form 97-98% of most vertebrate genomes.
In other words natural selection controls not only the "classical phenotype" of form and function (or, in molecular terms, of the proteins and of their expression), as generally accepted, but also the "genome phenotype", the compositional properties of the genome and all their functional implications. This occurs in such a way (by regional selection) that most of the changes are in fact neutral as proposed by Kimura. This leads to a picture in which the neutral theory and the regional selection are complementary facets of molecular evolution; this neo-selectionist theory of evolution was recently presented in a book (G. Bernardi, Structural and Evolutionary Genomics: Natural Selection in Genome Evolution, 2004). 

Representative Publications
Prof. Giorgio BernardiGiorgio Bernardi is the author or co-author of over 350 publications. 
The following is a list of some representative papers (including those quoted in the previous pages).
Bernardi G. (1965). Chromatography of nucleic acids on hydroxyapatite. Nature 206, 779-783.Bernardi G. (1968). Mechanism of action and structure of acid deoxyribonuclease. In Advances in Enzymology (F.F. Nord, ed.) 31, 1-49.Bernardi G. (1971). Chromatography of nucleic acids on hydroxyapatite columns. In Methods in Enzymology (L. Grossman and K. Moldave, eds.), vol. 21, pp. 95-139, Academic Press, New York.Bernardi G. (1971). Spleen acid deoxyribonuclease. In Enzymes , (P.D. Boyer, ed.), 3rd ed., vol. 4, pp. 271-287, Academic Press, New York.Bernardi G., Ehrlich S.D., Thiery J.P. (1973). The specificity of deoxyribonucleases and their use in nucleotide sequence studies. Nature New Biology 246, 36-40.Bernardi G. (1979). The petite mutation in yeast. Trends in Biochem. Sci. 4, 197-201Kettmann R., Meunier-Rotival M., Cortadas J., Cuny G., Ghysdael J., Mammerickx M., Burny A., Bernardi G. (1979). Integration of bovine leukemia virus DNA in the bovine genome. Proc. Natl. Acad. Sci. USA, 76, 4822-4826.Bernardi G. (1982b). The origins of replication of the mitochondrial genome of yeast. Trends in Biochem. Sci. 7, 404-408Soriano P., Meunier-Rotival M., Bernardi G. (1983). The distribution of interspersed repeats is non-uniform and conserved in the mouse and human genomes. Proc. Natl. Acad. Sci. USA 80, 1816-1820.Bernardi G. and Bernardi G. (1986a). Compositional constraints and genome evolution. J. Mol. Evol. 24, 1-11.Bernardi G., Olofsson B., Filipski J., Zerial M., Salinas J., Cuny G., Meunier-Rotival M., Rodier F. (1985). The mosaic genome of warm-blooded vertebrates. Science 228, 953-958
Goursot R., Goursot R., Bernardi G. (1988). Temperature can reversibly modify the structure and the functional efficiency of ori sequences of the mitochondrial genome from yeast. Gene, 69, 141-145.Bernardi G. (1989). The isochore organization of the human genome. Ann. Rev. Genet. 23, 637-661.Mouchiroud D., D'Onofrio G., Aïssani B., Macaya G., Gautier C. Bernardi G. (1991). The distribution of genes in the human genome. Gene 100, 181-187.Saccone S., De Sario A., Della Valle G., Bernardi G. (1992). The highest gene concentrations in the human genome are in T bands of metaphase chromosomes. Proc Natl Acad Sci USA 89, 4913-4917.Isacchi A., Bernardi G., Bernardi G. (1993). Compositional compartmentalization of the nuclear genomes of Trypanosoma brucei andTrypanosoma equiperdum. FEBS Letters, 335, 181-183.Saccone S., De Sario A., Wiegant J., Rap A.K., Della Valle G., Bernardi G. (1993). Correlations between isochores and chromosomal bands in the human genome. Proc. Natl. Acad. Sci. USA, 90, 11929-11933.Bernardi, G. (1995). The human genome : organization and evolutionary history. Annu. Rev. Genet. 29, 445-476.Carels N., Barakat A., Bernardi, G. (1995). The gene distribution of the maize genome. Proc. Natl. Acad. Sci. USA, 92, 11057-11060.De Sario A., Geigl E.M. and Bernardi G. (1995). A rapid procedure for the compositional analysis of yeast artificial chromosomes. Nucl. Acids Res., 23, 4013-4014.De Sario A., Geigl E.-M., Palmieri G. D'Urso, M., Bernardi G. (1996). A compositional map of human chromosome band Xq28. Proc. Natl. Acad. Sci. USA 93, 1298-1302Zoubak S., Clay O., Bernardi G. (1996). The gene distribution of the human genome. Gene 174, 95-102.Cacciò S., Jabbari K., Matassi G., Guermonprez F., Desgrès J., Bernardi G. (1997). Methylation patterns in the isochores of vertebrate genomes. Gene 205, 119-124Jabbari K., Cacciò S., Païs de Barros J.-P., Desgrès J., Bernardi G. (1997). Evolutionary changes in CpG and methylation levels in vertebrate genomes. Gene 205, 109-118Barakat A., Matassi G., Bernardi G. (1998). Distribution of genes in the genome of Arabidopsis thaliana and its implications for the genome organization of plants. Proc. Natl. Acad. Sci. USA, 95, 10044-10049.Rynditch A.V., Zoubak S., Tsyba L., Tryapitsina-Guley N., Bernardi G. (1998). The regional integration of retroviral sequences into the mosaic genomes of mammals. Gene 222, 1-16.Alvarez-Valin, F., Tort, J.F., Bernardi, G. (2000). Non-random spatial distribution of synonymous substitutions in the leishmania GP63 gene. Genetics 155, 1683-1692.Bernardi, G. (2000a). Isochores and the evolutionary genomics of vertebrates. Gene 241, 3-17.Bernardi, G. (2000b). The compositional evolution of vertebrate genomes. Gene 259(1-2), 31-43.Carels N. and Bernardi G. (2000). Two classes of genes in plants. Genetics 154: 1819-1825.Federico, C., Andreozzi, L., Saccone, S., and Bernardi, G. (2000). Gene density in the Giemsa bands of human chromosomes. Chromosome Research 8, 737-746.Saccone S., Pavlicek A., Federico C., Paces J., Bernardi G. (2001). Genes, isochores and bands in human chromosomes 21 and 22. Chromosome Research 9, 533-539.Pavlicek A, Clay O., Jabbari K, Paces J., Bernardi G (2002). Isochore conservation between MHC regions on human chromosome 6 and mouse chromosome 17. FEBS Letters 511, 175-177.Pavlicek A, Paces J, Clay O, Bernardi G (2002) A compact view of isochores in the draft human genome sequence. FEBS Letters 511, 165-169.Saccone S., Federico C., Bernardi G. (2002). Localization of the gene-richest and the gene-poorest isochores in the interphase nuclei of mammals and birds. Gene 300, 169-178.D'Onofrio G., Ghosh T.C., Bernardi G. (2002). The base composition of the genes is correlated with the secondary structures of the encoded proteins. Gene 300: 179-187.Alvarez-Valin F. , Lamolle G., Bernardi G. (2002). Isochores, GC3 and mutation biases in the human genome. Gene 300: 161-168.Cruveiller S., Jabbari K., Clay O., Bernardi G. (2003b). Compositional features of eukaryotic genomes for checking predicted genes. Brief. Bioinfor., 4:43-52.D'Onofrio G., Arhondakis S., Clay O., Bernardi G. (2004). Compositional features of vertebrate genomes and temperature are correlated. Gene (in press)Bernardi G. (2004). Structural and Evolutionary Genomics. Natural Selection in Genome Evolution. Elsevier, Amsterdam (in press) 


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