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An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Greedy Algorithms And Genome Rearrangements An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Turnip vs Cabbage: Look and Taste Different • Although cabbages and turnips share a recent common ancestor, they look and taste different An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Turnip vs Cabbage: Comparing Gene Sequences Yields No Evolutionary Information An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Turnip vs Cabbage: Almost Identical mtDNA gene sequences • In 1980s Jeffrey Palmer studied evolution of plants by comparing genomes of the cabbage and turnip • 99% similarity between genes • These surprisingly identical gene sequences differed in gene order • This study helped pave the way to analyzing genome rearrangements in molecular evolution An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Turnip vs Cabbage: Different mtDNA Gene Order • Gene order comparison: An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Turnip vs Cabbage: Different mtDNA Gene Order • Gene order comparison: An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Turnip vs Cabbage: Different mtDNA Gene Order • Gene order comparison: An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Turnip vs Cabbage: Different mtDNA Gene Order • Gene order comparison: An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Turnip vs Cabbage: Different mtDNA Gene Order • Gene order comparison: Before After Evolution is manifested as the divergence in gene order An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Transforming Cabbage into Turnip An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Genome rearrangements Mouse (X chrom.) Mouse Unknown ancestor ~ 75 million years ago Human (X chrom.) • What are the similarity blocks and how to find them? • What is the evolutionary scenario for transforming one genome into the other? An Introduction to Bioinformatics Algorithms www.bioalgorithms.info History of Chromosome X Rat Consortium, Nature, 2004 An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Reversals 1 2 3 9 8 4 7 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 • 6 Blocks represent conserved genes. 5 10 An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Reversals 1 2 3 9 8 4 7 1, 2, 3, -8, -7, -6, -5, -4, 9, 10 10 6 5 Blocks represent conserved genes. In the course of evolution or in a clinical context, blocks 1,…,10 could be misread as 1, 2, 3, -8, -7, -6, -5, -4, 9, 10. An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Reversals and Breakpoints 1 2 3 9 8 4 7 1, 2, 3, -8, -7, -6, -5, -4, 9, 10 10 6 5 The reversion introduced two breakpoints (disruptions in order). An Introduction to Bioinformatics Algorithms Reversals: Example www.bioalgorithms.info 5’ ATGCCTGTA ATGCCTGTACTA CCTGTACTA 3’ 3’ TACGGACAT TACGGACATGAT GGACATGAT 5’ Break and Invert 5’ ATGTACAGG ATGTACAGGCTA TACAGGCTA 3’ 3’ TACATGTCC TACATGTCCGAT ATGTCCGAT 5’ An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Types of Rearrangements Reversal 1 2 3 4 5 6 1 2 -5 -4 -3 6 Translocation 1 2 3 45 6 1 26 4 53 Fusion 1 2 3 4 5 6 1 2 3 4 5 6 Fission An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Comparative Genomic Architectures: Mouse vs Human Genome • Humans and mice have similar genomes, but their genes are ordered differently • ~245 rearrangements • Reversals • Fusions • Fissions • Translocation An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Waardenburg’s Syndrome: Mouse Provides Insight into Human Genetic Disorder • Waardenburg’s syndrome is characterized by pigmentary dysphasia • Gene implicated in the disease was linked to human chromosome 2 but it was not clear where exactly it is located on chromosome 2 An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Waardenburg’s syndrome and splotch mice • A breed of mice (with splotch gene) had similar symptoms caused by the same type of gene as in humans • Scientists succeeded in identifying location of gene responsible for disorder in mice • Finding the gene in mice gives clues to where the same gene is located in humans An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Comparative Genomic Architecture of Human and Mouse Genomes 10 11 12 13 14 15 16 17 18 19 X 9 Mouse 8 7 6 5 4 3 2 1 To locate where corresponding gene is in humans, we have to analyze the relative architecture of human and mouse genomes (b) Arrangement of human and mouse synteny blocks 1 2 3 4 5 6 7 8 9 10 Human 11 12 13 14 15 16 17 18 19 202122 X ERROR: invalidrestore OFFENDING COMMAND: restore STACK: -savelevel-savelevel[0.0 6.73077 -6.86046 0.0 4793.95 2365.38 ]