genome projects a genome project is the complete dna sequence of the genome of an organism, and the...
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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
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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
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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
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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
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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
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E. coli O157 genome
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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...
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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)
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Comparison of mouse and
human genomes
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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)…..
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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
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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