B o b G r o s s , B i o 6 8Genome OrganizationB o b G r o s s , B i o 3 9 / 1 3 9D.W. Mount, "Bioinformatics: Sequence and Genome Analyhsis" (2001), CSH PressTransposable ElementsB o b G r o s s , B i o 3 9 / 1 3 9Transposable Elements•thought to play significant role in evolution of genomes•can move from one chromosomal location to another faster than the chromosome can replicate•therefore, they can increase in number•remain detectable until mutations cause them to blend into backgroundB o b G r o s s , B i o 3 9 / 1 3 9Transposable Elements Types & SizesLong Interspersed Nuclear ElementsShort Interspersed Nuclear Elements10% of human genome is made up of a SINE called Alu (1.2 million copies!)14.6% of human genome is made up of a LINE called LINE1 (593,000 copies)promoter elementsD.W. Mount, "Bioinformatics: Sequence and Genome Analysis" (2001), CSH PressB o b G r o s s , B i o 3 9 / 1 3 9TEs and Genome Organizationpart of ß T-Cell receptor proteinstrypsin trypsin pseudogeneLTR elements have been inserted in last 3 million yearsD.W. Mount, "Bioinformatics: Sequence and Genome Analysis" (2001), CSH PressB o b G r o s s , B i o 3 9 / 1 3 9Modular Nature of GenesD.W. Mount, "Bioinformatics: Sequence and Genome Analysis" (2001), CSH PressB o b G r o s s , B i o 3 9 / 1 3 9Clustering of Similar Gene ModulesD.W. Mount, "Bioinformatics: Sequence and Genome Analysis" (2001), CSH PressB o b G r o s s , B i o 3 9 / 1 3 9Gene Order is ConservedD.W. Mount, "Bioinformatics: Sequence and Genome Analysis" (2001), CSH Pressortholog paralogB o b G r o s s , B i o 3 9 / 1 3 9Chromosomal RearrangementsD.W. Mount, "Bioinformatics: Sequence and Genome Analyhsis" (2001), CSH PressB o b G r o s s , B i o 3 9 / 1 3 9Gene Rearrangement in OperonsD.W. Mount, "Bioinformatics: Sequence and Genome Analyhsis" (2001), CSH PressB o b G r o s s , B i o 3 9 / 1 3 9•Clusters of Orthologous Groups of Proteins•Proteins that comprise each COG are assumed to have evolved from an ancestral protein•COGs were identified using an all-against-all sequence comparison of the proteins encoded in completely-sequenced genomes•A candidate protein is compared to another genome and the best match is found. If this best match is reciprocal then these proteins are part of a COG.•A COG must be comprised of one protein from at least three phylogenetically distant genomes•A member of a COG will be more similar to other members of the COG than to any other protein from the compared genomes, even if the absolute similarity is low.COGsCOGs: http://www.ncbi.nlm.nih.gov/COG/B o b G r o s s , B i o 3 9 / 1 3 9•Annotation of proteins:! Known functions (or 2D or 3D structures) of one COG member can often be directly attributed to the other members of the COG.! -Use caution - some COGs contain paralogs whose function may not precisely correspond to that of the known protein. •Phylogenetic patterns: These show the presence or absence of proteins from a given species in a specific COG.! Used systematically, such patterns can be used to identify whether a particular metabolic pathway exists in an species. •Multiple alignments:! Each COG page includes a link to a multiple alignment of COG members, which can be used to identify conserved sequence residues and analyze evolutionary relationships between member proteins. Uses of COGsCOG help: http://www.ncbi.nlm.nih.gov/COG/COGhelp.htmlB o b G r o s s , B i o 3 9 / 1 3 9B o b G r o s s , B i o 3 9 / 1 3 9B o b G r o s s , B i o 3 9 / 1 3 9Unicellular COG Tableplus many more...B o b G r o s s , B i o 3 9 / 1 3 9A COG SummaryB o b G r o s s , B i o 3 9 / 1 3 9An Alternative COG ViewB o b G r o s s , B i o 3 9 / 1 3 9B o b G r o s s , B i o 3 9 / 1 3 9KOG FamilyB o b G r o s s , B i o 3 9 / 1 3 9KOG1320 FamilyB o b G r o s s , B i o 3 9 / 1 3 9KOG1320 Family RelationshipsB o b G r o s s , B i o 3 9 / 1 3 9KOGnitor QueryB o b G r o s s , B i o 3 9 / 1 3 9KOGnitor OutputB o b G r o s s , B i o 3 9 / 1 3 9KOGnitor OutputB o b G r o s s , B i o 3 9 / 1 3 9KOGnitor OutputB o b G r o s s , B i o 3 9 / 1 3 9A Global COG TableB o b G r o s s , B i o 3 9 / 1 3 9Genome RearrangementsComparative Architectures of mammalian and chicken genomes reveal highly variable rates of genomic rearrangements across different lineagesGuillaume Borque, Evgeny M. Zdobnov, Peer Bork, Pavel A. Pevzner, and Glenn TeslerGenome Research 15:98-110 (2005)Comparative Genomicslarge amount of sequence data availableenables study of genomic organization beyond just individual genesreveals more rearrangements than we previously thoughtsheds light on previously unknown featuresGenome Rearrangement Studiesidentify orthologous genes in different genomesidentify synteny blocks (orthologous regions in genomes)find most parsimonious scenario of rearrangements to explain current genome organizationsCurrent Paper Approachconsider two different types of evidence to establish orthologous genomic regionsDNA-DNA alignments called sequence-based dataprotein-protein alignments called gene-based datathen apply GRIMM-Synteny to determine synteny blocksuse these blocks as input to Multiple Genome Rearrangement algorithms<http://www-cse.ucsd.edu/groups/bioinformatics/software.html>GRIMM SyntenyGRIMM: Genome Rearrangement In Man and Mousefinds an optimal scenario to transform one genome architecture into another using translocations, inversions, fissions and fusionsa unichromosomal genome is a sequence of n genestwo orientations of a gene are i and -ia unichromosomal genome with n = 5 might be 5 4 -3 2 -1"Genome Rearrangements in Mammalian Evolution: Lessons From Human and Mouse Genomes" by P. Pevzner and G. Tesler; Genome Research 13:37–45 (2003)GRIMM Syntenymultichromosomal genome consists of n genes on m chromosomesuse a ‘$’ as delimiter to generate, for example, 12 genes on 3 chromosomes as:7 -2 8 3 $ 5 9 -6 -1 12 $11 4 10 $7 -2 8 -4 -11 $5 9 -12 1 6 $-3 10 $7 -2 8 3 $5 9 -6 -1 12 $11 4 10 $Rearrangements7 -2 8 3 $5 9 -6 -1 12 $11 4 10 $7 -2 8 3 $5 9 -12 1 6 $11 4 10 $reversal(inversion)translocation7 -2 8 3 $5 9 -6 -1 12 $11 4 10 $7 -2 8 3 $5 9 -6 -1 12 $11 4 10 $7 -2 8 3 -10 -4 -11 $5 9 -12 1 6 $7 -2 8 3 $5 9 -6 -1 12 $11 4 10 $RearrangementsfusionfissionBreakpointsearly studies talked about …