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Gustavo Henrique Goldman, Ph.D. Laboratório de Biologia Molecular

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1 Gustavo Henrique Goldman, Ph.D. Laboratório de Biologia Molecular
Bloco Q, FCFRP-USP Telefones: , e -4311 goldman.fcfrp.usp.br

Programa Aulas Teóricas: 1) Introdução 2) As células e os genomas 3) A química da célula 4) As proteínas 5) O DNA e os cromossomas 6) A replicação, o reparo e a recombinação do DNA 7) Do DNA para a proteína: como as células lêem o genoma 8) O controle da expressão gênica 9) A manipulação do DNA, RNA e proteínas 10) O ciclo celular e a morte celular programada 11) O câncer

3 Programa Aulas Práticas de Bioinformática:
1) A análise e a aquisição de seqüências genômicas 2) As seqüências genômicas respondem a questões interessantes 3) As variações genômicas 4) A pesquisa básica com microarrays de DNA 5) A pesquisa aplicada com microarrays de DNA 6) A proteômica 7) Os circuitos genômicos em genes isolados 8) Os circuitos genômicos integrados 9) A modelagem de circuitos genômicos 10) A transição da genética para a genômica: o estudo de casos médicos

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

5 Horários: Curso Integral Terças-feiras: Curso Teórico 14:00 às 16:00 hs Curso Prático 8:00 às 10:00 hs (Turma A) Curso Prático 16:00 às 18:00 hs (Turma B) Laboratório de Física e Físico-Química Curso Noturno Quartas-feiras: Curso Teórico 19:00 às 21:00 hs Curso Prático 21:00 às 23:00 hs

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








14 The three major divisions (domains) of the living world

15 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

16 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


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

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

20 “(...) 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 ”

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

22 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



25 “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”

26 Horizontal gene transfers in early evolution


28 A mutant phenotype reflecting the function of a gene

29 The genome of E. coli


31 “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 ”


33 The origin of mitochondria


35 The origin of chroroplasts

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

37 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)

38 The puffer fish (Fugu rubripes)
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

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


41 Arabidopsis thaliana

42 Caenorhabditis elegans

43 Drosophila melanogaster

44 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

45 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

46 The consequences of gene duplication for mutational analysis of gene function


48 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.

49 Human and mouse: similar genes and similar development
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

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