Biologia Genômica. 2º Semestre, 2017

(1)

Biologia Genômica

2º Semestre, 2017

Prof. Marcos Túlio Oliveira

Departamento de Tecnologia

Programa de Pós-Graduação em Biociências

mtoliveria@fcav.unesp.br

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.

(2)

Biologia Genômica

(3)

(4)

(5)

http://virtuallaboratory.colorado.edu/Biofundamentals/lectureNotes-Revision/Topic4-2_GeneExp.htm

(6)

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...

(7)

www.fcav.unesp.br/mtoliveira

Protein Science (2008), 17:385–388

(8)

http://www.sciencephoto.com/media/209697/view http://www.novusbio.com/Fas-Antibody_NBP1-89034.html

(9)

Overview

(10)

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

(11)

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

(12)

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

(13)

FIGURE 03: The number of genes in bacterial and archaeal genomes is proportional to genome size

(14)

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

(15)

FIGURE 05: The S. cerevisiae genome of 13.5 Mb has 6000 genes, almost all uninterrupted

(16)

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

(17)

(18)

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.

(19)

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

(20)

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

(21)

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.

(22)

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.

(23)

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

(24)

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

(25)

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

(26)

Estrutura

(27)

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.

(28)

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

(29)

(30)

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

[http://www.sciencedirect.com/science/journal/00928674]. Photo courtesy of Ulrich K. Laemmli, University of Geneva, Switzerland.

(31)

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

(32)

(33)

Molecular Biology of the Gene, 2003.

Estrutura dos cromossomos

Célula humana contém 3 x 10

9

pb (haplóide)

Comprimento de um pb é 3.4 Å

Comprimento do genoma humano é 10

10

Å

1 metro!!!

(34)

Estrutura dos cromossomos

Célula humana contém 3 x 10

9

pb (haplóide)

Comprimento de um pb é 3.4 Å

Comprimento do genoma humano é 10

10

Å

1 metro!!!

(35)

(36)

(37)

(38)

(39)

(40)

(41)

(42)

Estrutura da cromatina “higher order”

(43)

(44)

(45)

(46)

(47)

(48)

(49)

(50)

(51)

(52)

(53)

(54)