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Biologia Genômica
2º Semestre, 2017
Prof. Marcos Túlio Oliveira
Departamento de Tecnologia
Programa de Pós-Graduação em Biociências
www.fcav.unesp.br/mtoliveria
Faculdade de Ciências Agrárias e Veterinárias de Jaboticabal
Instituto de Biociências, Letras e Ciências Exatas de S.J.R.P.
Universidade Estadual Paulista “Júlio de Mesquita Filho”
Biologia Genômica
Biologia Genômica
http://virtuallaboratory.colorado.edu/Biofundamentals/lectureNotes-Revision/Topic4-2_GeneExp.htm
Biologia Genômica
Apresentações dos alunos
24/03
Replicação do bacteriófago T4
Replicação do bacteriófago ϕX174
Replicação do plasmídeo ColE1
Replicação do DNA cloroplastidial
Replicação do vírus SV40
Replicação do vírus HIV
14/04
Surgimento de genes “de novo”
28/04
O genoma do homen de Neandertal
O genoma do homen de Denisova
O genoma do chimpanzé
05/05
O genoma de Arabidopsis thaliana
O genoma de Saccharomyces cerevisiae
O genoma de Drosophila melanogaster
O genoma do camundongo
O genoma do boi
O genoma da cana-de-açúcar
O genoma de Xanthomonas
Outros genomas...
www.fcav.unesp.br/mtoliveira
Protein Science (2008), 17:385–388
Biologia Genômica
http://www.sciencephoto.com/media/209697/view http://www.novusbio.com/Fas-Antibody_NBP1-89034.html
Procariotos Eucariotos
Overview
Molecular Biology of the Gene, 2003.
6.1 Introduction FIGURE 01: The minimum gene number required for any type of organism
increases with its complexity
Photo of intracellular bacterium courtesy of Gregory P. Henderson and Grant J. Jensen, California Institute of Technology
Photo of free-living bacterium courtesy of Karl O. Stetter, Universität Regensburg
Photo of unicellular eukaryote courtesy of Eishi Noguchi, Drexel University College of Medicine
Photo of multicellular eukaryote courtesy of Carolyn B. Marks and David H. Hall, Albert Einstein College of Medicine, Bronx, NY
Lewin’s Genes X, 2009.
FIGURE 01: The minimum gene number required for any type of organism increases with its complexity
6.1 Introduction
Photo of higher plant courtesy of Keith Weller/USDA
Photo of mammal © Photodisc
Lewin’s Genes X, 2009.
6.2 Prokaryotic Gene Numbers Range Over
an Order of Magnitude
• The minimum number of
genes for a parasitic
prokaryote is about 500;
for a free-living
nonparasitic prokaryote it
is about 1500.
FIGURE 02: Genome sizes and gene numbers are known from complete
sequences for several organisms
Lewin’s Genes X, 2009.
FIGURE 03: The number of genes in bacterial and archaeal genomes is proportional to genome size
Lewin’s Genes X, 2009.
6.3 Total Gene Number Is Known for
Several Eukaryotes
• There are 6000 genes in yeast; 18,500 in a worm; 13,600 in a fly; 25,000 in the small plant Arabidopsis; and probably 20,000 to 25,000 in mice and humans.
FIGURE 04: The number of genes in a eukaryote varies
from 6000 to 40,000 but does not
correlate with the genome size or the complexity of the
organism
Lewin’s Genes X, 2009.
FIGURE 05: The S. cerevisiae genome of 13.5 Mb has 6000 genes, almost all uninterrupted
FIGURE 12: The average human gene is 27 kb long and has nine exons, usually comprising two longer exons at each end and seven internal exons
Lewin’s Genes X, 2009.
Molecular Biology of the Gene, 2003.
6.3 Total Gene Number Is Known for Several Eukaryotes
FIGURE 06: Functions are known for only half the fly genes
Adapted from Drosophila 12 Genomes Consortium, Nature 450 (2007): 203-218.
Lewin’s Genes X, 2009.
6.4 How Many Different Types of Genes Are
There?
• The sum of the number of unique genes and the number
of gene families is an estimate of the number of types of
genes.
FIGURE 07: Many genes are duplicated, and as a
result the number of different gene families is much less than the total
number of genes
Lewin’s Genes X, 2009.
6.4 How Many Different Types of Genes Are There?
• orthologous genes
(orthologs) – Related
genes in different
species.
• The minimum size of
the proteome can be
estimated from the
number of types of genes.
FIGURE 09: The fly genome
Lewin’s Genes X, 2009.
6.5 The Human Genome Has Fewer Genes
Than Originally Expected
• Only 1% of the human genome consists of exons.
• The exons comprise ~5% of each gene, so genes (exons plus introns) comprise ~25% of the genome.
• The human genome has 20,000 to 25,000 genes.
Lewin’s Genes X, 2009.
6.7 The Y Chromosome Has Several
Male-Specific Genes
• The Y chromosome has ~60 genes that are expressed
specifically in the testis.
• The male-specific genes are present in multiple copies in
repeated chromosomal segments.
• Gene conversion between multiple copies allows the
active genes to be maintained during evolution.
FIGURE 15: The Y chromosome consists
of X-transposed regions, X-
degenerate regions, and amplicons
Lewin’s Genes X, 2009.
6.8 How Many Genes Are Essential?
• Not all genes are essential. In yeast and flies, deletions of <50% of the genes have detectable effects.
• When two or more genes are redundant, a mutation in any one of them may not have detectable effects.
FIGURE 16: Essential yeast genes are found in all classes
Lewin’s Genes X, 2009.
6.8 How Many Genes Are Essential?
• We do not fully understand the persistence of genes that
are apparently dispensable in the genome.
FIGURE 17: A systematic analysis of loss of function for 86% of worm genes shows that only 10% have detectable effects on the phenotype
Lewin’s Genes X, 2009.
6.9 About 10,000 Genes Are Expressed at Widely Differing Levels in a Eukaryotic Cell
FIGURE 20: Hybridization between excess mRNA and cDNA
FIGURE 21: The abundances of yeast mRNAs vary
Lewin’s Genes X, 2009.
Estrutura
Cromossomos, cromatina e nucleossomos
9.3 The Bacterial Genome Is a Nucleoid
• The bacterial nucleoid is ~80% DNA by mass and can be
unfolded by agents that act on RNA or protein.
• The proteins that are responsible for condensing the
DNA have not been identified.
Photo courtesy of the Molecular and Cell Biology Instructional Laboratory Program, University of California, Berkeley.
FIGURE 05: A thin section shows the bacterial nucleoid as a compact mass in
the center of the cell
Lewin’s Genes X, 2009.
Estrutura dos cromossomos
9.4 The Bacterial Genome Is Supercoiled
• The nucleoid has ~400
independent negatively
supercoiled domains.
• The average density of
supercoiling is ~1
turn/100bp.
FIGURE 07: The bacterial genome consists of a large number of
loops of duplex DNA
Lewin’s Genes X, 2009.
9.5 Eukaryotic DNA Has Loops and
Domains Attached to a Scaffold
• DNA of interphase chromatin
is negatively supercoiled into
independent domains of ~85
kb.
• Metaphase chromosomes
have a protein scaffold to
which the loops of
supercoiled DNA are
attached.
FIGURE 09: Histone-depleted chromosomes consist of a protein scaffold to which loops of
DNA are anchored Reprinted from Cell, vol. 12, J. R. Paulson and U. K. Laemmli, The structure of histone-depleted
metaphase chromosomes, pp. 817-828. Copyright 1977, with permission from Elsevier
[http://www.sciencedirect.com/science/journal/00928674]. Photo courtesy of Ulrich K. Laemmli,
University of Geneva, Switzerland.
Lewin’s Genes X, 2009.
9.7 Chromatin Is Divided into Euchromatin
and Heterochromatin
• Individual chromosomes can be seen only during mitosis.
• During interphase, the general mass of chromatin is in the
form of euchromatin, which is slightly less tightly packed
than mitotic chromosomes.
FIGURE 12: Regions of compact heterochromatin are clustered near the nucleolus and nuclear
membrane
Photo courtesy of Edmund Puvion, Centre National de la Recherche Scientifique Lewin’s Genes X, 2009.
Molecular Biology of the Gene, 2003.
Molecular Biology of the Gene, 2003.
Estrutura dos cromossomos
Célula humana contém 3 x 109 pb (haplóide)
Comprimento de um pb é 3.4 Å
Comprimento do genoma humano é 1010 Å
1 metro!!!
Diplóide = 2 metros de DNA por célula!
Molecular Biology of the Gene, 2003.
Estrutura dos cromossomos
Célula humana contém 3 x 109 pb (haplóide)
Comprimento de um pb é 3.4 Å
Comprimento do genoma humano é 1010 Å
1 metro!!!
Diplóide = 2 metros de DNA por célula!
Molecular Cell Biology, 5ª edição.
Molecular Biology of the Gene, 2003.
Molecular Biology of the Gene, 2003.
Molecular Biology of the Gene, 2003.
Molecular Biology of the Gene, 2003.
Molecular Biology of the Gene, 2003.
Molecular Biology of the Gene, 2003.
Estrutura da cromatina “higher order”
Molecular Biology of the Gene, 2003.
Molecular Biology of the Gene, 2003.
H1
Molecular Biology of the Gene, 2003.
Molecular Biology of the Gene, 2003.
Molecular Biology of the Gene, 2003.
Molecular Biology of the Gene, 2003.
Molecular Biology of the Gene, 2003.
Molecular Biology of the Gene, 2003.
Molecular Biology of the Gene, 2003.
Molecular Cell Biology, 5ª edição.
Molecular Biology of the Gene, 2003.
Molecular Biology of the Gene, 2003.
Biologia Genômica
2º Semestre, 2017
Prof. Marcos Túlio
Próxima aula: Replicação de DNA bacteriano
e nuclear
Faculdade de Ciências Agrárias e Veterinárias de Jaboticabal
Instituto de Biociências, Letras e Ciências Exatas de S.J.R.P.
Universidade Estadual Paulista “Júlio de Mesquita Filho”