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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
Chapter 21
Genomes and Their Evolution
Lectures by
Erin Barley
Kathleen Fitzpatrick
© 2011 Pearson Education, Inc.
Overview: Leaves from the Tree of Life
• Human Genome Project
• Other genomes that have been sequenced
– Chimpanzee
– E. coli
– rhesus macaque
- fruit fly
- house mouse
- watermelon
• Comparison gives info about the 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.
Concept 21.1: New approaches have
accelerated the pace of genome sequencing
• Human Genome Project started in 1990
mostly complete by 2003 – 2001 James Kent vs. Craig Venter
• 3 stages of project
– Genetic (or linkage) mapping
– Physical mapping
– DNA sequencing
© 2011 Pearson Education, Inc.
Figure 21.2-4
Chromosome
bands
Cytogenetic map
Genes located
by FISH
1 Linkage mapping
Genetic
markers
2 Physical mapping
Overlapping
fragments
3 DNA sequencing
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.
• 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.
Whole-Genome Shotgun Approach to
Genome Sequencing
• The whole-genome shotgun approach was
developed by J. Craig Venter (jerk) in 1992
• skips first two steps
– Sequences DNA fragments directly
• Powerful computer programs are used to order
fragments into a continuous sequence
• James Kent – linux cluster
© 2011 Pearson Education, Inc.
Figure 21.3-3
1 Cut the DNA into
overlapping fragments short enough
for sequencing.
2 Clone the fragments
in plasmid or phage
vectors.
3 Sequence each
fragment.
4 Order the
sequences into
one overall
sequence
with computer
software.
• Both 3-stage process & whole-genome shotgun
method were used
• Early skepticism about the whole-genome
shotgun approach
• Now one of most common methods
• Faster and cheaper now than ever
http://www.npr.org/blogs/health/2012/10/02/161110956/will-low-costgenome-sequencing-open-pandoras-box
© 2011 Pearson Education, Inc.
• Metagenomics: Sequencing the DNA from a
group of species (a metagenome) collected from
an environmental sample
• Example: sequencing the DNA in a mixed
population of microbes
• No need to grow individual species in the lab
© 2011 Pearson Education, Inc.
Concept 21.2 Scientists use bioinformatics
to analyze genomes and their functions
• The Human Genome Project established
databases make data available on the Internet
– Venter planned to charge researchers to see data
– Kent made it available for free.
• This has accelerated progress in DNA sequence
analysis
© 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.
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
• Researchers disables genes in yeast, one pair at a
time
– Double mutants (mutant for two genes)
• 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.
Figure 21.5
Glutamate
biosynthesis
Translation and
ribosomal functions
Mitochondrial
functions
Vesicle
fusion
RNA processing
Peroxisomal
functions
Transcription
and chromatinrelated functions
Metabolism
and amino acid
biosynthesis
Nuclearcytoplasmic
transport
Secretion
and vesicle
transport
Nuclear migration
and protein
degradation
Mitosis
DNA replication
and repair
Cell polarity and
morphogenesis
Protein folding,
glycosylation, and
cell wall biosynthesis
Serinerelated
biosynthesis
Amino acid
permease pathway
Application of Systems Biology to Medicine
• A systems biology approach has several medical
applications
–
–
–
–
The Cancer Genome Atlas project
Cataloged mutations in three types of cancer
compares normal and cancer cell genes
Good results: will try on other cancers
© 2011 Pearson Education, Inc.
Figure 21.6
Silicon and glass “chips”
have been produced
that hold a microarray
of most known human
genes
Genomes vary in size,
# of genes, & density
© 2011 Pearson Education, Inc.
Genomes vary in size, # of genes, & density
© 2011 Pearson Education, Inc.
Number of Genes
• Free-living bacteria and archaea have 1,500 to
7,500 genes
• Unicellular fungi have from about 5,000 genes
and multicellular eukaryotes up to at least 40,000
genes
• Humans: estimated ~25,000
© 2011 Pearson Education, Inc.
• # of genes != genome size
• Nematode C. elegans: 100 Mb and 20,000 genes
fly Drosophila: 65 Mb and 13,700 genes
• Vertebrate genomes can produce more than one
polypeptide per gene because of alternative
splicing of RNA transcripts
© 2011 Pearson Education, Inc.
Gene Density and Noncoding DNA
• Humans and other mammals have the lowest
gene density, or number of genes, in a given
length of DNA
• Multicellular eukaryotes have many introns within
genes and noncoding DNA between genes
© 2011 Pearson Education, Inc.
Concept 21.4: non-coding DNA
• Most of DNA in genome does not encode proteins
or functional RNAs
• The noncoding DNA (previously called “junk
DNA”) plays important roles in the cell
– ENCODE project
• genomes of humans, rats, and mice show high
sequence conservation for about 500 noncoding
regions
– DNA that doesn’t matter is not conserved
© 2011 Pearson Education, Inc.
• Sequencing of the human genome reveals that
98.5% does not code for proteins, rRNAs, or
tRNAs
• About a quarter of the human genome codes for
introns and gene-related regulatory sequences
© 2011 Pearson Education, Inc.
• Intergenic DNA is noncoding DNA found between
genes
– Pseudogenes are former genes that have
accumulated mutations and are nonfunctional
– Repetitive DNA is present in multiple copies in
the genome
• About three-fourths of repetitive DNA is made up
of transposable elements and sequences related
to them
• http://genome.ucsc.edu/ENCODE/
© 2011 Pearson Education, Inc.
Jumping Genes and Related Sequences
• Barbara McClintock: Indian corn
• Color changes due to DNA segments that move
around in genome
© 2011 Pearson Education, Inc.
Jumping Genes and Related Sequences
• These transposable elements move from one
site to another in a cell’s DNA; they are present in
both prokaryotes and eukaryotes
• Eukaryotic transposable elements are of two
types
– Transposons, which move by means of a DNA
intermediate
– Retrotransposons, which move by means of an
RNA intermediate
© 2011 Pearson Education, Inc.
Figure 21.9
Transposon
DNA of
genome
Transposon
is copied
Mobile transposon
New copy of
transposon
Insertion
Figure 21.10
Retrotransposon
New copy of
retrotransposon
Formation of a
single-stranded
RNA intermediate
RNA
Insertion
Reverse
transcriptase
Other Repetitive DNA, Including Simple
Sequence DNA
• About 15% of the human DNA is long duplicates
• In contrast, simple sequence DNA contains
many copies of tandemly repeated short
sequences
© 2011 Pearson Education, Inc.
• A series of repeating units of 2 to 5 nucleotides is
called a short tandem repeat (STR)
• The repeat number for STRs can vary among
sites (within a genome) or individuals
• Simple sequence DNA is common in
centromeres and telomeres, where it probably
plays structural roles in the chromosome
© 2011 Pearson Education, Inc.
Genes and Multigene Families
• Many eukaryotic genes are present in one copy
per haploid set of chromosomes
• multigene families, collections of identical or
very similar genes
• Some multigene families consist of identical DNA
sequences, usually clustered tandemly, such as
those that code for rRNA products
© 2011 Pearson Education, Inc.
Duplication of Entire Chromosome Sets
• Polyploidy - extra sets of chromosomes (e.g 3n)
• Accidents in meiosis cause polyploidy
• these variations might be passed on to kids
© 2011 Pearson Education, Inc.
Duplication of Entire Chromosome Sets
• Polyploidy: Extra copies can mutate
• not lethal - you still have one functional copy
• Mutated extra copy might become gene for new form of
protein
© 2011 Pearson Education, Inc.
Alterations of Chromosome Structure
Human: 23 chromosomes pairs
Chimp: 24 chromosome pairs
Why? Fusion of chromosomes
© 2011 Pearson Education, Inc.
• chromosomal duplications and inversions are
thought to contribute to the generation of new
species
• Chromosomal rearrangements are more frequent
during periods of rapid evolution (e.g. among
survivors after a die off)
• “hot spots” in genome associated with
chromosomal rearrangement are also associated
with diseases
© 2011 Pearson Education, Inc.
Duplication and Divergence of Gene-Sized
Regions of DNA
Unequal crossing over
during prophase I of
meiosis can result in
one chromosome with
a deletion and
another with a
duplication of a
particular region
© 2011 Pearson Education, Inc.
Duplication of Entire Chromosome Sets
• Polyploidy: Extra copies can mutate
• not lethal - you still have one functional copy
• Mutated extra copy might encode a new form of protein
• New functions can be different from original
• Lysozyme (fight infection)  α-lactalbumin (milk production)
© 2011 Pearson Education, Inc.
Exon Shuffling: errors in meiosis
© 2011 Pearson Education, Inc.
How Transposable Elements cause Genome
Evolution
• Insertion of transposable elements within a
protein-coding sequence may block protein
production
• nsertion of transposable elements within a
regulatory sequence may increase or decrease
protein production
© 2011 Pearson Education, Inc.
How Transposable Elements cause Genome
Evolution
• Transposable elements may carry a gene or
groups of genes to a new position
• Transposable elements may also create new
sites for alternative splicing in an RNA transcript
• In all cases, changes are usually detrimental but
may on occasion prove advantageous to an
organism
© 2011 Pearson Education, Inc.
Concept 21.6: Comparing genome
sequences provides clues to evolution and
development
• Genome comparisons of closely related species
help us understand recent evolutionary events
• Genome comparisons of distantly related species
help us understand ancient evolutionary events
© 2011 Pearson Education, Inc.
Comparing Genomes
• Genome comparisons of closely related species
help us understand recent evolutionary events
• Genome comparisons of distantly related species
help us understand ancient evolutionary events
© 2011 Pearson Education, Inc.
Relationships among species can be
represented by a tree-shaped diagram
Comparing Distantly Related Species
• Highly conserved genes have changed very little
over time
• These help clarify relationships among species
that diverged from each other long ago
© 2011 Pearson Education, Inc.
Comparing Distantly Related Species
• Bacteria, archaea, and eukaryotes are thought to
have diverged from each other between 2 and 4
billion years ago
• Highly conserved genes can be studied in one
model organism, and the results applied to other
organisms
© 2011 Pearson Education, Inc.
Comparing Genomes Within a Species
• Most human variation is due to single nucleotide
polymorphisms, inversions, deletions, and
duplications
• These variations are useful for studying human
evolution and human health
© 2011 Pearson Education, Inc.
Comparing Developmental Processes
• Evolutionary developmental biology, or evo-devo,
is the study of the evolution of developmental
processes in multicellular organisms
• Genomic information shows that minor differences
in gene sequence or regulation can result in
striking differences in form
© 2011 Pearson Education, Inc.
Widespread Conservation of Developmental
Genes Among Animals
• Molecular analysis of the homeotic genes in
Drosophila has shown that they all include a
sequence called a homeobox
• An identical or very similar nucleotide sequence
has been discovered in the homeotic genes of
both vertebrates and invertebrates
• Homeobox genes code for a domain that allows a
protein to bind to DNA and to function as a
transcription regulator
• Homeotic genes in animals are called Hox genes
© 2011 Pearson Education, Inc.
Figure 21.18
Adult
fruit fly
Fruit fly embryo
(10 hours)
Fly chromosome
Mouse
chromosomes
Mouse embryo
(12 days)
Adult mouse
• Sometimes small changes in regulatory
sequences of certain genes lead to major
changes in body form
• For example, variation in Hox gene expression
controls variation in leg-bearing segments of
crustaceans and insects
• In other cases, genes with conserved sequences
play different roles in different species
© 2011 Pearson Education, Inc.
Figure 21.19
Thorax
Genital
segments
Thorax
Abdomen
Abdomen
Comparison of Animal and Plant
Development
• In both, development relies turning genes on or
off in a finely tuned series (transcription regulators)
• Mads-box genes in plants are the regulatory
equivalent of Hox genes in animals
© 2011 Pearson Education, Inc.
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