Download E. coli

Genome Projects
• A genome project is the complete DNA
sequence of the genome of an organism, and
the identification of all its genes
• Genome projects are possible because of the
large-scale, automated application of
molecular genetic techniques (cloning and
sequencing)
• There are now complete genome projects
for all major groups of organism
Complete genome sequences
• Total 908 species,
including 172
eukaryotes, either
completely
sequenced or in
progress
• NCBI genome website:
• http://www.ncbi.nlm.nih.gov/Genomes/index.html
Which organisms?
• Pathogens - such as bacteria
• Model organisms - Drosophila (fruit fly), C
elegans (nematode worm), mouse, which
have been used in genetics for many years
• Agricultural organisms - rice, wheat, cattle
• Human
DNA
sequencing
by dideoxy
method
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Automated
DNA
sequencing
(fluorescent
dideoxy
method)
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Technology
• Top-down for big genomes - based on first
making a map
• Bottom-up or shotgun for little genomes
such as bacteria
• Top-down approach uses bottom-up method
on mapped bits of genome
Shotgun: contigs
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• Contigs are identified
from sequence
overlaps
• In a bacterial
genome, a specific
11bp sequence is
likely to be unique
(411 > 4,000,000)
• In human genome it’s
16bp (416 >
4,000,000,000)
Maps and shotgun
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Bios
Publishers
Ltd
A pathogen
• The E coli O157 genome webpage
• 5.5 Mb of DNA on 1 chromosome
• 5324 protein-coding genes and 128
structural RNA-coding genes
E. coli O157 genome
A model organism
•
•
•
•
The Drosophila genome webpage
137 Mb of DNA on 4 chromosomes
13500 genes
A view of the genome can be seen here...
The human genome
• The human genome webpage
• About 3000 Mb of DNA on 23
chromosomes
• About 35000 genes (only about twice as
many as flies and worms)
• Most human genes have homologues in
other organisms (vertebrates, insects, yeast
etc)
Comparison
of mouse and
human
genomes
Identifying the genes
(open reading frames)
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Identifying genes with introns
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Variations in DNA sequence
• Because of shotgun sequencing, the genome was
sequenced several times from different people’s
DNA
• This allows DNA polymorphisms to be found
• The amount of DNA variation between organisms
is a measure of how closely related they are
• It can be measured by comparing homologous
genes (i.e. genes with a common evolutionary
origin)…..
Homology - 2 DNA sequences
with 80% identity
• By repeating this analysis over many loci
you can get an accurate picture of the
evolutionary history of the organisms
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The origins of humans
• There are 2 main theories on the origin of modern humans:
– Multiregional: early human (Homo erectus) left Africa 1,000,000
Ya and evolved separately into modern humans in many places
– Out-of-Africa: populations of Homo erectus around the world were
displaced by the ancestors of modern humans, migrating from
Africa 50,000 - 100,000 Ya
• These can be investigated by studying genetic variation in
modern humans from around the world
• The Y-chromosome (passed from fathers to sons) and
mitochondrial genomes (passed from mothers to all
children) are often used for these studies
The multiregional hypothesis
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Bios
Publishers
Ltd
The Out-of-Africa hypothesis
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Bios
Publishers
Ltd
Molecular genetics supports Outof-Africa
• Of all modern humans’ mitochondrial DNA,
the oldest types are found in Africans
• By calculating the rate at which mutation
has occurred (molecular clock) can see that
our common ancestor lived 140,000 290,000 Ya