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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 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 Copyright Bios Publishers Ltd Automated DNA sequencing (fluorescent dideoxy method) Copyright Bios Publishers Ltd 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 Copyright Bios Publishers Ltd • 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 Copyright 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) Copyright Bios Publishers Ltd Identifying genes with introns Copyright Bios Publishers Ltd 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 Copyright Bios Publishers Ltd 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 Copyright Bios Publishers Ltd The Out-of-Africa hypothesis Copyright 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