MIT6_047f08_lec02_note02

MIT6_047f08_lec02_note02 - MIT OpenCourseWare...

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Unformatted text preview: 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 . 6.047/6.878 Lecture 2- Sequence Alignment and Dynamic Programming September 15, 2008 1 Introduction Evolution has preserved functional elements in the genome. Such elements often manifest themselves as homologues , or similar sequences in descendants of a common ancestor. The two main types of homologous sequences are orthologous and paralogous sequences. Orthologous sequences typically have similar functions in both the ancestor and the descendant and arise through speciation events, while paralagous sequences arise from common ancestors through gene duplication. Furthermore, paralagous genes imply a common ancestor but, due to mutation and evolution the functionality of that particular gene has shifted considerably. We will mostly be interested in studying orthologous gene sequences. Aligning sequences is one of the main ways of discovering such similarities between different ancestors. And in solving sequence alignment problems, the primary computational tool will be Dynamic Programming . 1.1 An Example Alignment Within orthologus gene sequences, there are islands of conservation which are relatively large stretches of nucleotides that are preserved between generations. These conserved elements typically imply functional elements and vice versa. Although, note that conservation is sometimes just random chance. As an example, we considered the alignment of the Gal10-Gal1 intergenic region for four different yeast species, the first whole genome alignment for crosspieces (Page 1 Slide 5). As we look at this alignment, we note some areas that are more conserved than others. In particular, we note some small conserved motifs such as CGG and CGC , which in fact are functional elements in the binding of Gal4. This example illustrates how we can read evolution to find functional elements. Figure 1: Sequence alignment of Gal10-Gal1. 1 1.2 Genome Changes are Symmetric The genome changes over time. In studying these changes, well confine ourselves to the level of nucleotide mutations, such as substitutions, insertions and deletions of bases. Lacking a time machine, we cannot compare genomes of living species with their ancestors, so were limited to just comparing the genomes of living descendants. For our purposes, time becomes a reversible concept. This means that we can consider the events that change a genome from one species to another as occurring in reverse order (tracing up an evolutionary tree towards a common ancestor) or forward order (tracing downwards from a common ancestor). We consider all DNA changes to be symmetric in time: an insertion in one direction is equivalent to a deletion in the other....
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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_lec02_note02 - MIT OpenCourseWare...

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