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Genomes and Their Evolution - Napa Valley 120...Genomes and Their Evolution Chapter 21 Tree of Life...

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  • 11/25/2011

    1

    LECTURE PRESENTATIONS

    For CAMPBELL BIOLOGY, NINTH EDITION Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson

    2011 Pearson Education, Inc.

    Lectures by

    Erin Barley

    Kathleen Fitzpatrick

    Genomes and Their Evolution

    Chapter 21 Overview: Reading the Leaves from the

    Tree of Life

    Complete genome sequences exist for a human,

    chimpanzee, E. coli, brewers yeast, corn, fruit fly,

    house mouse, rhesus macaque, and other

    organisms

    Comparisons of genomes among organisms

    provide information about the evolutionary history

    of genes and taxonomic groups

    2011 Pearson Education, Inc.

    Genomics is the study of whole sets of genes

    and their interactions

    Bioinformatics is the application of

    computational methods to the storage and

    analysis of biological data

    2011 Pearson Education, Inc.

    Figure 21.1

    Concept 21.1: New approaches have

    accelerated the pace of genome sequencing

    The most ambitious mapping project to date has been the sequencing of the human genome

    Officially begun as the Human Genome Project in 1990, the sequencing was largely completed by 2003

    The project had three stages

    Genetic (or linkage) mapping

    Physical mapping

    DNA sequencing 2011 Pearson Education, Inc.

    Three-Stage Approach to Genome

    Sequencing

    A linkage map (genetic map) maps the location

    of several thousand genetic markers on each

    chromosome

    A genetic marker is a gene or other identifiable

    DNA sequence

    Recombination frequencies are used to

    determine the order and relative distances

    between genetic markers

    2011 Pearson Education, Inc.

  • 11/25/2011

    2

    Figure 21.2-1

    Cytogenetic map

    Genes located

    by FISH

    Chromosome

    bands

    Figure 21.2-2

    Cytogenetic map

    Genes located

    by FISH

    Chromosome

    bands

    Linkage mapping

    Genetic

    markers

    1

    Figure 21.2-3

    Cytogenetic map

    Genes located

    by FISH

    Chromosome

    bands

    Linkage mapping

    Genetic

    markers

    1

    Physical mapping 2

    Overlapping

    fragments

    Figure 21.2-4

    Cytogenetic map

    Genes located

    by FISH

    Chromosome

    bands

    Linkage mapping

    Genetic

    markers

    1

    Physical mapping 2

    Overlapping

    fragments

    DNA sequencing 3

    A physical map expresses the distance between

    genetic markers, usually as the number of base

    pairs along the DNA

    It is constructed by cutting a DNA molecule into

    many short fragments and arranging them in

    order by identifying overlaps

    2011 Pearson Education, Inc.

    Sequencing machines are used to determine the

    complete nucleotide sequence of each

    chromosome

    A complete haploid set of human chromosomes

    consists of 3.2 billion base pairs

    2011 Pearson Education, Inc.

  • 11/25/2011

    3

    Whole-Genome Shotgun Approach to

    Genome Sequencing

    The whole-genome shotgun approach was

    developed by J. Craig Venter in 1992

    This approach skips genetic and physical mapping

    and sequences random DNA fragments directly

    Powerful computer programs are used to order

    fragments into a continuous sequence

    2011 Pearson Education, Inc.

    Cut the DNA into overlapping frag- ments short enough for sequencing.

    1

    Clone the fragments in plasmid or phage vectors.

    2

    Figure 21.3-1

    Cut the DNA into overlapping frag- ments short enough for sequencing.

    1

    Clone the fragments in plasmid or phage vectors.

    2

    Sequence each fragment.

    3

    Figure 21.3-2 Cut the DNA into overlapping frag- ments short enough for sequencing.

    1

    Clone the fragments in plasmid or phage vectors.

    2

    Sequence each fragment.

    3

    Order the sequences into one overall sequence with computer software.

    4

    Figure 21.3-3

    Both the three-stage process and the whole-

    genome shotgun approach were used for the

    Human Genome Project and for genome

    sequencing of other organisms

    At first many scientists were skeptical about the

    whole-genome shotgun approach, but it is now

    widely used as the sequencing method of choice

    The development of newer sequencing

    techniques has resulted in massive increases in

    speed and decreases in cost

    2011 Pearson Education, Inc.

    Technological advances have also facilitated

    metagenomics, in which DNA from a group of

    species (a metagenome) is collected from an

    environmental sample and sequenced

    This technique has been used on microbial

    communities, allowing the sequencing of DNA of

    mixed populations, and eliminating the need to

    culture species in the lab

    2011 Pearson Education, Inc.

  • 11/25/2011

    4

    Concept 21.2 Scientists use bioinformatics

    to analyze genomes and their functions

    The Human Genome Project established

    databases and refined analytical software to make

    data available on the Internet

    This has accelerated progress in DNA sequence

    analysis

    2011 Pearson Education, Inc.

    Centralized Resources for Analyzing

    Genome Sequences

    Bioinformatics resources are provided by a

    number of sources

    National Library of Medicine and the National

    Institutes of Health (NIH) created the National

    Center for Biotechnology Information (NCBI)

    European Molecular Biology Laboratory

    DNA Data Bank of Japan

    BGI in Shenzhen, China

    2011 Pearson Education, Inc.

    Genbank, the NCBI database of sequences, doubles its data approximately every 18 months

    Software is available that allows online visitors to search Genbank for matches to

    A specific DNA sequence

    A predicted protein sequence

    Common stretches of amino acids in a protein

    The NCBI website also provides 3-D views of all protein structures that have been determined

    2011 Pearson Education, Inc.

    Figure 21.4

    Identifying Protein-Coding Genes and

    Understanding Their Functions

    Using available DNA sequences, geneticists can

    study genes directly in an approach called reverse

    genetics

    The identification of protein coding genes within

    DNA sequences in a database is called gene

    annotation

    2011 Pearson Education, Inc.

    Gene annotation is largely an automated process

    Comparison of sequences of previously unknown

    genes with those of known genes in other species

    may help provide clues about their function

    2011 Pearson Education, Inc.

  • 11/25/2011

    5

    Understanding Genes and Gene

    Expression at the Systems Level

    Proteomics is the systematic study of all proteins

    encoded by a genome

    Proteins, not genes, carry out most of the

    activities of the cell

    2011 Pearson Education, Inc.

    How Systems Are Studied: An Example

    A systems biology approach can be applied to define gene circuits and protein interaction networks

    Researchers working on the yeast Saccharomyces cerevisiae used sophisticated techniques to disable pairs of genes one pair at a time, creating double mutants

    Computer software then mapped genes to produce a network-like functional map of their interactions

    The systems biology approach is possible because of advances in bioinformatics

    2011 Pearson Education, Inc.

    Translation and ribosomal functions

    Nuclear- cytoplasmic

    transport

    RNA processing

    Transcription and chromatin-

    related functions

    Mitochondrial functions

    Nuclear migration and protein degradation

    Mitosis

    DNA replication and repair

    Cell polarity and morphogenesis

    Protein folding, glycosylation, and

    cell wall biosynthesis

    Secretion and vesicle transport

    Metabolism and amino acid biosynthesis

    Peroxisomal functions

    Glutamate biosynthesis

    Serine- related

    biosynthesis

    Amino acid permease pathway

    Vesicle fusion

    Figure 21.5 Figure 21.5a

    Translation and ribosomal functions

    Nuclear- cytoplasmic

    transport

    RNA processing

    Transcription and chromatin-

    related functions

    Mitochondrial functions

    Nuclear migration and protein degradation

    Mitosis

    DNA replication and repair

    Cell polarity and morphogenesis

    Protein folding, glycosylation, and

    cell wall biosynthesis

    Secretion and vesicle transport

    Metabolism and amino acid

    biosynthesis

    Peroxisomal functions

    Glutamate biosynthesis

    Serine- related

    biosynthesis

    Amino acid permease pathway

    Vesicle fusion

    Metabolism and amino acid

    biosynthesis

    Figure 21.5b

    Application of Systems Biology to Medicine

    A systems biology approach has several medical

    applications

    The Cancer Genome Atlas project is currently

    seeking all the common mutations in three types

    of cancer by comparing gene sequences and

    expression in cancer versus normal cells

    This has been so fruitful, it will be extended to

    ten other common cancers

    Silicon and glass chips have bee

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