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Gustavo Henrique Goldman, Ph.D. Laboratrio de Biologia Molecular Bloco Q, FCFRP-USP Telefones: 6024280, -4281 e -4311 e-mail: ggoldman@usp.brggoldman@usp.br goldman.fcfrp.usp.br

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CURSO DE BIOLOGIA MOLECULAR Programa Aulas Tericas: 1) Introduo 2) As clulas e os genomas 3) A qumica da clula 4) As protenas 5) O DNA e os cromossomas 6) A replicao, o reparo e a recombinao do DNA 7) Do DNA para a protena: como as clulas lem o genoma 8) O controle da expresso gnica 9) A manipulao do DNA, RNA e protenas 10) O ciclo celular e a morte celular programada 11) O cncer

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Programa Aulas Prticas de Bioinformtica: 1) A anlise e a aquisio de seqncias genmicas 2) As seqncias genmicas respondem a questes interessantes 3) As variaes genmicas 4) A pesquisa bsica com microarrays de DNA 5) A pesquisa aplicada com microarrays de DNA 6) A protemica 7) Os circuitos genmicos em genes isolados 8) Os circuitos genmicos integrados 9) A modelagem de circuitos genmicos 10) A transio da gentica para a genmica: o estudo de casos mdicos

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Referncias: 1) Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., Walter, P., 2002. Molecular Biology of the Cell, fourth edition, Garland Science. 2) Campbell, A.M., Heyer, L.J., 2003. Genomics, Proteomics, & Bioinformatics, CSHL Press, Benjamin Cummings. 3) Koonin, E.V., Galperin, M.Y., 2003. Sequence Evolution-function Computational Approaches in Comparative Genomics. Norwell (MA): Kluwer Academic Publishers www.ncbi.nlm.nih.gov Critrios de Avaliao: Provas, seminrios, listas de exerccios Datas das provas: Primeira Prova: 28/09 e 29/09/2004 Segunda Prova: 07/12 e 08/12/2004

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Horrios: Curso Integral Teras-feiras:Curso Terico 14:00 s 16:00 hs Curso Prtico 8:00 s 10:00 hs (Turma A) Curso Prtico 16:00 s 18:00 hs (Turma B) Laboratrio de Fsica e Fsico-Qumica Curso Noturno Quartas-feiras:Curso Terico 19:00 s 21:00 hs Curso Prtico 21:00 s 23:00 hs

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The whole of biology is a counterpart between the two themes: astonishing variety in individual particulars; astonishing constancy in fundamental mechanisms

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The three major divisions (domains) of the living world

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Genetic information conserved since the beginnings of life. A part of the gene for the smaller of the two main RNA components (16 S, 1550 nucleotides long) of the ribosome is shown

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Mycoplasma genitalium (580,070 nucleotide pairs): 477 genes: (i) 37 code for transfer, ribosomal, and other nonmessenger RNAs; (ii) 297 of the genes coding for proteins: -153 are involved in DNA replication, transcription, and translation and related processes; - 29 in the membrane and surface structures of the cell; - 33 in the transport of nutrients; -71 in energy conversion and the synthesis and degradation of small molecules; - and 11 in the regulation of cell division and other processes

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Four modes of genetic innovation and their effects on the DNA sequence of an organism

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(...) it has been estimated that at least 18 % of all the genes in the present-day genome of E. coli have been acquired by horizontal transfer from another species within the past 100 million years

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Families of evolutionarily related genes in the genome of Bacillus subtilis. The biggest family consists of 77 genes coding for varieties of ABC transporters

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Paralogous genes and orthologous genes: two types of gene homology based on different evolutionary pathways. (A) and (B) The most basic possibilities. (C) A more complex pattern of events that can occur

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At a molecular level, archae seem to resemble eukaryotes more closely in their machinery for handling genetic information (replication, transcription, and translation), but eubacteria more closely in their apparatus for metabolism and energy conversion

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Horizontal gene transfers in early evolution

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A mutant phenotype reflecting the function of a gene

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The genome of E. coli

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Eukaryotes not only have more genes than prokaryotes, they also have vastly more DNA that does not code for protein or for any other functional product molecule. The human genome contains a 1000 times as many nucleotide pairs as the genome of a typical bacterium, 20 times as many genes, and about 10,000 times as much noncoding DNA (~ 98.5 % of the genome for a human is noncoding, as opposed to 11 % of the genome for the bacterium E. coli

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The origin of mitochondria

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The origin of chroroplasts

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Genome sizes compared. Genome size is measured in nucleotide pairs of DNA per haploid genome, that is, per single copy of the genome

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Saccharomyces cerevisiae = 13,117,000 nucleotide pairs (about 6,300 genes) Neurospora crassa = 40 Mb (about 10,500 genes) Drosophila melanogaster = 170 Mb (about 14,000 genes) Caenorhabditis elegans = 97 Mb (about 19,000 genes) Arabidopsis thaliana = 140 Mb (about 25,500 genes)

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The puffer fish (Fugu rubripes). This organism has a genome size of 400 million nucleotide pairs about one-quarter as much as a zebrafish, for example, even though the two species of fish have similar numbers of genes

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Genetic control of the program of multicellular development. Antirrhinum sp.

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Arabidopsis thaliana

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Caenorhabditis elegans

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Drosophila melanogaster

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Giant chromosomes from salivary gland cells of Drosophila. Because many rounds of DNA replication have occurred without an intervening cell division, each of the chromosomes in these unusual cells contains over a 1000 identical DNA molecules, all aligned in register

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Two species of the frog genus Xenopus. X. tropicalis, above, has an ordinary diploid Genome; X. laevis, below, has twice as much DNA per cell

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The consequences of gene duplication for mutational analysis of gene function

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Times of divergence of different Vertebrates. On average within any particular evolutionary lineage, hemoglobins accumulate changes at a rate of about 6 altered amino acids per 100 amino acids every 100 million years. Some proteins subject to stricter functional constraints, evolve much more slowly than this, other as much as 5 times faster.

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Human and mouse: similar genes and similar development. The human baby and the mouse shown here have similar white patches on their foreheads because both have mutations in the same gene (called kit), required for the development and maintenance of pigment cells