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Transcript
Genome Rearrangements Belle marquise, vos beaux yeux me font mourir d'amour. Vos yeux beaux d'amour me font, belle marquise, mourir. Me font vos beaux yeux mourir, belle marquise, d'amour. Anne Bergeron, Comparative Genomics Laboratory Université du Québec à Montréal 1. General introduction to genome rearrangements Examples of rearranged genomes 2. Measures of distance Rearrangement operations The Hannenhalli-Pevzner distance equation 3. A unifying view of genome rearrangements The Double-Cut-and-Join operation The adjacency graph and the distance equation 1. General introduction to genome rearrangements Examples of rearranged genomes 2. Measures of distance Rearrangement operations The Hannenhalli-Pevzner distance equation 3. A unifying view of genome rearrangements The Double-Cut-and-Join operation The adjacency graph and the distance equation Example of rearranged genomes : Mitochondrial Genomes Mitochondria are small, oval shaped organelles surrounded by two highly specialized membranes. Homo sapiens Bombyx mori Animal mitochondrial genomes are normally circular, ~16 kB in length, and encode: 13 proteins 22 tRNAs and 2 rRNAs. Example of rearranged genomes : Mitochondrial Genomes Here is an alignment of the cytochrome c oxidase I of, respectively, Homo sapiens and Bombyx mori. RWLFSTNHKDIGTLYLLFGAWAGVLGTALSLLIRAELGQPGNLLGNDHIYNVIVTAHAFVMIFFMVMPIMIGGFGNWLVPLMIGAPDMAFPRMNNM KWIYSTNHKDIGTLYFIFGIWSGMIGTSLSLLIRAELGNPGSLIGDDQIYNTIVTAHAFIMIFFMVMPIMIGGFGNWLVPLMLGAPDMAFPRMNNM :*::***********::** *:*::**:**********:**.*:*:*:***.*******:**********************:************* :X::XXXXXXXXXXX::XX X:X::XX:XXXXXXXXXX:XX.X:X:X:XXX.XXXXXXX:XXXXXXXXXXXXXXXXXXXXXX:XXXXXXXXXXXXX SFWLLPPSLLLLLASAMVEAGAGTGWTVYPPLAGNYSHPGASVDLTIFSLHLAGVSSILGAINFITTIINMKPPAMTQYQTPLFVWSVLITAVLLLLSLP SFWLLPPSLMLLISSSIVENGAGTGWTVYPPLSSNIAHSGSSVDLAIFSLHLAGISSIMGAINFITTMINMRLNNMSFDQLPLFVWAVGITAFLLLLSLP *********:**::*::** XXXXXXXXXXXX:.X XXXXXXXXX:XX::X::XX ************:.* :*.*:****:********:***:********:***: :X.X:XXXX:XXXXXXXX:XXX:XXXXXXXX:XXX: *: X: * X *****:* XXXXX:X ***.******* XXX.XXXXXXX VLAAGITMLLTDRNLNTTFFDPAGGGDPILYQHLFWFFGHPEVYILILPGFGMISHIVTYYSGKKEPFGYMGMVWAMMSIGFLGFIVWAHHMFTVGMDVD VLAGAITMLLTDRNLNTSFFDPAGGGDPILYQHLFWFFGHPEVYILILPGFGMISHIISQESGKKETFGCLGMIYAMLAIGLLGFIVWAHHMFTVGMDID ***..************:***************************************:: *****.** XXX..XXXXXXXXXXXX:XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX:: XXXXX.XX :**::**::**:****************:* :XX::XX::XX:XXXXXXXXXXXXXXXX:X TRAYFTSATMIIAIPTGVKVFSWLATLHGSNMKWSAAVLWALGFIFLFTVGGLTGIVLANSSLDIVLHDTYYVVAHFHYVLSMGAVFAIMGGFIHWFPLF TRAYFTSATMIIAVPTGIKIFSWLATMHGTQINYNPNILWSLGFVFLFTVGGLTGVILANSSIDITLHDTYYVVAHFHYVLSMGAVFAIIGGFINWYPLF *************:***:*:******:**:::::.. :**:***:**********::*****:**.***********************:****:*:*** XXXXXXXXXXXXX:XXX:X:XXXXXX:XX:::::.. :XX:XXX:XXXXXXXXXX::XXXXX:XX.XXXXXXXXXXXXXXXXXXXXXXX:XXXX:X:XXX SGYTLDQTYAKIHFTIMFIGVNLTFFPQHFLGLSGMPRRYSDYPDAYTTWNILSSVGSFISLTAVMLMIFMIWEAFASKRKVLMVEEPSMNLE TGLSLNSYMLKIQFFTMFIGVNMTFFPQHFLGLAGMPRRYSDYPDSYISWNMISSLGSYISLLSVMMMLIIIWESMINQRINLFSLNLPSSIE :* :X:. :X :*:. XX:X **:* XXXXXX:XXXXXXXXXX:XXXXXXXXXXX:X ******:**********:***********:* :**::**:**:*** :XX::XX:XX:XXX :**:*:::***:: :XX:X:::XXX:: .:* .:X *: X: : . .:* .:X 73% identity over more than 500 amino acids. Example of rearranged genomes : Mitochondrial Genomes The 37 genes of animal mitochondria are highly conserved. Charles Darwin, 1809 - 1882 A lowly worm But the order of the genes differs from species to species. Example of rearranged genomes : Mitochondrial Genomes The invariant parts Homo sapiens mitochondrial genome (proteins and rRNAs) COX1 COX2 ATP6 ATP8 COX3 ND3 ND4L ND4 ND5 CYTB RNS RNL ND1 ND2 ND6 COX1 stands for the gene cytochrome c oxidase I. Bombyx mori mitochondrial genome (proteins and rRNAs) COX1 COX2 ATP6 ATP8 COX3 ND3 ND6 ND5 COX1 stands for the gene cytochrome c oxidase I. ND4 ND4L CYTB ND2 ND1 RNL RNS Example of rearranged genomes : Mitochondrial Genomes The modified parts Homo sapiens mitochondrial genome (proteins and rRNAs) COX1 COX2 ATP6 ATP8 COX3 ND3 ND4L ND4 ND5 CYTB RNS RNL ND1 ND2 ND6 Bombyx mori mitochondrial genome (proteins and rRNAs) COX1 COX2 ATP6 ATP8 COX3 ND3 ND6 ND5 ND4 ND4L CYTB ND2 ND1 RNL RNS Example of rearranged genomes : Mitochondrial Genomes of 6 Arthropoda Fruit Fly Mosquito Silkworm Locust Tick Centipede Identical ‘runs’ of genes have been grouped. Example of rearranged genomes : mammal X chromosomes Sixteen large synteny blocks are ordered differently in the X chromosomes of the human, mouse and rat. Blocks have similar gene content and order. Note that the estimated number of genes in the X chromosome is 2000. (Art work by Guillaume Bourque, scientific work by Guillaume Bourque, Pavel Pevzner and Glenn Tesler, 2004) Example of rearranged genomes : mammal X chromosomes QuickTime™ and a decompressor are needed to see this picture. (Art work by Guillaume Bourque, scientific work by Guillaume Bourque, Pavel Pevzner and Glenn Tesler, 2004) Problem: Given two or more genomes, How do we measure their similarity and/or distance with respect to gene order and gene content? Sub-problem: How do we know that two genes or blocks are the "same" in two different species? 1. General introduction to genome rearrangements Examples of rearranged genomes 2. Measures of distance Rearrangement operations The Hannenhalli-Pevzner distance equation 3. A unifying view of genome rearrangements The Double-Cut-and-Join operation The adjacency graph and the distance equation Rearrangement operations Rearrangement operations affect gene order and gene content. There are various types: • Inversions • Transpositions • Reverse transpositions • Translocations, fusions and fissions • Duplications and losses • Others... Any set of operations yields a distance between genomes, by counting the minimum number of operations needed to transform one genome into the other. Rearrangement operations • Inversions Rearrangement operations • Inversions Rearrangement operations • Inversions Example: Mitochondrial Genomes of 6 Arthropoda An inversion. Fruit Fly Mosquito Silkworm Locust Tick Centipede Rearrangement operations • Transpositions Rearrangement operations • Transpositions Rearrangement operations • Transpositions Example: Mitochondrial Genomes of 6 Arthropoda Fruit Fly Mosquito Silkworm Locust Tick A transposition Centipede Rearrangement operations • Reverse transpositions Rearrangement operations • Reverse transpositions Rearrangement operations • Reverse transpositions Example: Mitochondrial Genomes of 6 Arthropoda Fruit Fly Mosquito Silkworm Locust A reverse transposition Tick Centipede Rearrangement operations • Translocations, fusions and fissions Rearrangement operations • Translocations, fusions and fissions Rearrangement operations • Translocations, fusions and fissions Rearrangement operations • Translocations, fusions and fissions Rearrangement operations • Translocations, fusions and fissions Rearrangement operations • Translocations, fusions and fissions From 24 chromosomes To 21 chromosomes [Source: Linda Ashworth, LLNL] DOE Human Genome Program Report 1. General introduction to genome rearrangements Examples of rearranged genomes 2. Measures of distance Rearrangement operations The Hannenhalli-Pevzner distance equation 3. A unifying view of genome rearrangements The Double-Cut-and-Join operation The adjacency graph and the distance equation The Hannenhalli-Pevzner distance equation In 1995, Hannenhalli and Pevzner found a formula to compute the minimum number of inversions, translocations, fusions or fissions necessary to transform a multichromosomal genome into another. Sketch of the approach: • Cap the chromosomes • Concatenate all the chromosomes • Sort the resulting genome by inversions QuickTime™ and a decompressor are needed to see this picture. 1. General introduction to genome rearrangements Examples of rearranged genomes 2. Measures of distance Rearrangement operations The Hannenhalli-Pevzner distance equation 3. A unifying view of genome rearrangements The Double-Cut-and-Join operation The adjacency graph and the distance equation The Double-Cut-and-Join operation Acts on up to 4 gene extremities: , , , Reminder Yancopoulos et al. 2005 The Double-Cut-and-Join operation Linear chromosomes Translocation Translocation Translocation Translocation Reminder Translocation Translocation The Double-Cut-and-Join operation Linear and circular chromosomes Inversion Inversion Fusion Fusion Fission Reminder Fission The Double-Cut-and-Join operation Circular chromosomes Inversion Inversion Fusion Fusion Fission Reminder Fission 1. General introduction to genome rearrangements Examples of rearranged genomes 2. Measures of distance Rearrangement operations The Hannenhalli-Pevzner distance equation 3. A unifying view of genome rearrangements The Double-Cut-and-Join operation The adjacency graph and the distance equation 4. Breakpoint reuse Breakpoint reuse estimates Minimizing breakpoint reuse The adjacency graph and the distance equation Genome A 3 5 2 4 1 6 Genome B 1 2 5 Joint work with Julia Mixtacki and Jens Stoye 3 6 4 The adjacency graph and the distance equation Genome A Genome B 3 1 5 2 2 3 Joint work with Julia Mixtacki and Jens Stoye 4 4 1 5 6 6 The adjacency graph and the distance equation Genome A Genome B 3 1 5 2 2 3 Joint work with Julia Mixtacki and Jens Stoye 4 4 1 5 6 6 The adjacency graph and the distance equation Genome A Genome B 3 1 5 2 2 3 Joint work with Julia Mixtacki and Jens Stoye 4 4 1 5 6 6 The adjacency graph and the distance equation Genome A Genome B 3 1 5 2 2 3 Joint work with Julia Mixtacki and Jens Stoye 4 4 1 5 6 6 The adjacency graph and the distance equation Genome A Genome B 3 1 5 2 2 3 Joint work with Julia Mixtacki and Jens Stoye 4 4 1 5 6 6 The adjacency graph and the distance equation Genome A Genome B 3 1 5 2 2 3 C = number of cycles I = number of odd paths G = number of “genes” Joint work with Julia Mixtacki and Jens Stoye 4 4 1 5 D = G - (C + I/2) D = 6 - (1 + 2/2) = 4 6 6
