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This Friday 10am Beckman B-200 Introduction to text processing lingos. Lecture 3. Genome Content: Repetitive Sequences Genes. Our Place in the Tree of Life. you are here. [Human Molecular Genetics, 3rd Edition]. Metazoans (multi-cellular organisms). you are here.
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This Friday 10am Beckman B-200 Introduction to text processing lingos. http://cs273a.stanford.edu [Bejerano Fall09/10]
Lecture 3 Genome Content: Repetitive Sequences Genes http://cs273a.stanford.edu [Bejerano Fall09/10]
Our Place in the Tree of Life you are here [Human Molecular Genetics, 3rd Edition] http://cs273a.stanford.edu [Bejerano Fall09/10]
Metazoans (multi-cellular organisms) you are here [Human Molecular Genetics, 3rd Edition] http://cs273a.stanford.edu [Bejerano Fall09/10]
Vertebrates , Stickleback , Lizard , Opossum you are here [Human Molecular Genetics, 3rd Edition] http://cs273a.stanford.edu [Bejerano Fall09/10]
INTERSPECIES VARIATION IN GENOME SIZE WITHIN VARIOUS GROUPS OF ORGANISMS Figure from Ryan Gregory (2005)
Meet Your Genome Continues [Human Molecular Genetics, 3rd Edition] http://cs273a.stanford.edu [Bejerano Fall09/10]
Repeats / obile Elements ("selfish DNA") Human Genome: 3*109 letters 1.5% known function >50% junk http://cs273a.stanford.edu [Bejerano Fall09/10]
[Adapted from Lunter] http://cs273a.stanford.edu [Bejerano Fall09/10]
TE composition and assortment vary among eukaryotic genomes 100% 80% 60% DNA transposons LTR Retro. 40% Non-LTR Retro. 20% Rice Fugu Mouse Human Mosquito Nematode Slime mold Drosophila Neurospora Arabidopsis Fission yeast Budding yeast http://cs273a.stanford.edu [Bejerano Fall09/10] Feschotte & Pritham 2006
Assemby Challenges http://cs273a.stanford.edu [Bejerano Fall09/10]
Inferring Phylogeny Using Repeats [Nishihara et al, 2006] http://cs273a.stanford.edu [Bejerano Fall09/10]
Functional elements from obile Elements Co-option event, probably due to favorable genomic context [Yass is a small town in New South Wales, Australia.] [Bejerano et al., Nature 2006] http://cs273a.stanford.edu [Bejerano Fall09/10]
The amount of TE correlate positively with genome size Mb Genomic DNA 3000 2500 TE DNA 2000 Protein-coding DNA 1500 1000 500 0 Rice Mosquito Maize Slime mold Brassica Plasmodium Sea squirt Neurospora Arabidopsis Fugu Drosophila Nematode Zebrafish Mouse Fission yeast Budding yeast Human http://cs273a.stanford.edu [Bejerano Fall09/10] Feschotte & Pritham 2006
The proportion of protein-coding genes decreases with genome size, while the proportion of TEs increases with genome size TEs Protein-coding genes http://cs273a.stanford.edu [Bejerano Fall09/10] Gregory, Nat Rev Genet 2005
Genome Size Variability 1pg = 978 Mb http://cs273a.stanford.edu [Bejerano Fall09/10]
Simple Repeats • Every possible motif of mono-, di, tri- and tetranucleotide repeats is vastly overrepresented in the human genome. • These are called microsatellites,Longer repeating units are called minisatellites,The real long ones are called satellites. • Highly polymorphic in the human population. • Highly heterozygous in a single individual. • As a result microsatellites are used in paternity testing, forensics, and the inference of demographic processes. • There is no clear definition of how many repetitions make a simple repeat, nor how imperfect the different copies can be. • Highly variable between genomes: e.g., using the same search criteria the mouse & rat genomes have 2-3 times more microsatellites than the human genome. They’re also longer in mouse & rat. http://cs273a.stanford.edu [Bejerano Fall09/10]
Restriction enzymes recognize and make a cut within specific palindromic sequences, known as restriction sites, in the DNA. This is usually a 4- or 6 base pair sequence. blunt end sticky end http://cs273a.stanford.edu [Bejerano Fall09/10]
DNA Fingerprint Basics DNA fragments of different size will be produced by a restriction enzyme that cuts at the points shown by the arrows. http://cs273a.stanford.edu [Bejerano Fall09/10]
DNA fragments are then separated based on size using gel electrophoresis. http://cs273a.stanford.edu [Bejerano Fall09/10]
DNA Fingerprinting can be used in paternity testing or murder cases. http://cs273a.stanford.edu [Bejerano Fall09/10]
From an evolutionary point of view transposons and simple repeats are very different. Different instances of the same transposon share common ancestry (but not necessarily a direct common progenitor). Different instances of the same simple repeat most often do not. http://cs273a.stanford.edu [Bejerano Fall09/10]
The Gene-ome makes < 2% of the H.G. [Human Molecular Genetics, 3rd Edition] http://cs273a.stanford.edu [Bejerano Fall09/10]
Gene Structure Signal – a string of DNA recognized by the cellular machinery http://cs273a.stanford.edu [Bejerano Fall09/10]
Gene Processing Eukaryotic Gene Structure http://cs273a.stanford.edu [Bejerano Fall09/10]
Gene Finding – The Practice Challenge: “The genes, the whole genes, and nothing but the genes” Problems: spliced ESTs legitimate gene isoform? predicting gene isoforms tissue/condition-specific genes / gene isoforms single exon genes pseudogenes Practice: http://cs273a.stanford.edu [Bejerano Fall09/10]
Evolution of Gene Finding Tools etc http://cs273a.stanford.edu [Bejerano Fall09/10]
The Human Gene Set [HGC, 2001] http://cs273a.stanford.edu [Bejerano Fall09/10]
[Celera, 2001] http://cs273a.stanford.edu [Bejerano Fall09/10]
wrong! http://cs273a.stanford.edu [Bejerano Fall09/10]
Signal Transduction http://cs273a.stanford.edu [Bejerano Fall09/10]
Ancient Origins of Important Gene Families http://cs273a.stanford.edu [Bejerano Fall09/10]
Multigene families due to: • Single gene duplication; • Segment duplication: Tandem duplication or duplication transposition • a b c d e f g • a b c d e f b c d g • Horizontal gene transfer; • Genome-wide doubling event http://cs273a.stanford.edu [Bejerano Fall09/10]
Horizontal Gene Transfer http://cs273a.stanford.edu [Bejerano Fall09/10]
Horizontal Gene Transfer in the H.G. … [HGC, 2001] http://cs273a.stanford.edu [Bejerano Fall09/10]
Or is it? [Kurland et al., 2003] http://cs273a.stanford.edu [Bejerano Fall09/10]
HGT between fish & their parasites http://cs273a.stanford.edu [Bejerano Fall09/10]
