MIT6_047f08_lec15_note15

MIT6_047f08_lec15_note15 - MIT OpenCourseWare...

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MIT OpenCourseWare http://ocw.mit.edu 6.047 / 6.878 Computational Biology: Genomes, Networks, Evolution Fall 2008 For information about citing these materials or our Terms of Use, visit: http://ocw.mit.edu/terms .
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Lecture 15 - Comparative Genomics I: Genome annotation 11 / 23 / 08 1 Introduction This lecture and the next will discuss the recent and current research in comparative genomics being performed in Professor Kellis’ lab. Comparative genomics allows one to infer understanding of genomes from the study of the evolution of closely related species, and vice-versa. This lecture will discuss the use of evolution to understand genomes, and lecture 16 will deal with using genomes to better understand evolution. By understanding genomes, we mean primarily to annotate the various parts: protein coding regions, regulatory motifs, etc. We’ll see later that comparative genomics also allows us to uncover completely new ways various elements are processed that we would not recognize using other methods. In Dr. Kellis’ lab, mammals, flies and fungi are studied. Slide 6 shows the many species that are part of the data sets that are analyzed. We want to study a wide variety of organisms to observe elements that are at di erent distances from humans. This allows the study of processes at di erent ranges of evolution (di erent snapshots in time based on divergence point). There are several reasons why it is important to have closely related species as well as more distantly related species. More closely related species should have very similar functional elements and randomness in the non-functional elements. This is because selection weeds out disrupting mutations in functional regions, and mutations accumulate in the non-functional regions. More distantly related species will likely have significant di erences in both their functional and non-functional elements. Phylogeny allows observation of individual events that may be di cult to resolve in species that are more separated. However, our signal relies on the ability to identify / observe an evolutionary event, thus if we look only at species that are close, there won’t be enough changes to discriminate between functional and non-functional regions. More distantly related species allow us to better identify neutral substitutions. 2 Preliminary steps in comparative genomics Once we have our sequence data (or if we have a new sequence that we wish to annotate), we begin with multiple alignments of the sequences. We BLAST regions of the genome against other genomes, and then apply sequence alignment techniques to align individual regions to a reference genome for a pair of species. We then perform a series of pairwise alignments walking up the phylogeny until we have an alignment for all sequences. Because we can align every gene and every intergenic region, we don’t just have to rely on conserved regions, we can align every single region regardless of whether the conservation in that region is su cient to allow genome wide 1
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placement across the species. This is because we have ’anchors’ spanning entire regions, and we
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This note was uploaded on 09/24/2010 for the course EECS 6.047 / 6. taught by Professor Manoliskellis during the Fall '08 term at MIT.

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MIT6_047f08_lec15_note15 - MIT OpenCourseWare...

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