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

• NCBI genome website:

• http://www.ncbi.nlm.nih.gov/Genomes/index.html

• Total 908 species, including 172 eukaryotes, either completely sequenced or in progress

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

• 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)

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Maps and shotgun

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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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The Out-of-Africa hypothesis

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Molecular genetics supports Out-of-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