Comparative Genomics

What is Comparative Genomics? It is the comparison of one genome to another. Genomics DNA (Gene) Functional Transcriptomics RNA Proteomics PROTEIN Metabolomics METABOLITE Transcription Translation Enzymatic reaction

How is it different from what we’ve already covered and been doing in class?

How is it different from what we’ve already covered and been doing in class? When we BLAST a sequence is that comparative genomics?

Difference is in Scale and Direction Other “omics” Comparative One or several genes compared against all other known genes. Entire Genome compared to other entire genomes. Use information from many genomes to learn more about the individual genes. Use genome to inform us about the entire organism.

What are some questions that comparative genomics can address? How has the organism evolved? What differentiates species? Which non-coding regions are important? Which genes are required for organisms to survive in a certain environment?

Different Questions Require Different Comparisons From: Hardison. Plos Biology. Vol 1 (2): 156-160

From: Miller et al. Annu. Rev. Genom. Human. Genet. 2004.5:15-56.

Example of a Comparative Genomic Study: Kellis et al. 2003. Nature. 423:241-254. Purpose of the paper is to use the genomes of three closely related Saccharomyces strains to inform our knowledge about S. cerevisiae.

First step is to align the genomes as above First step is to align the genomes as above. Several webtools are available for genome alignment and other comparative tasks. For some go to http://www.dcode.org/

By comparing the genomes they not only found numerous new regulatory motifs, but they were able to reduce the total S. cerevisiae gene estimate by 500. The authors could have also focused their comparisons on what parts of these similar genomes account for each strain’s uniqueness instead just focusing on gaining insights into S. cerevisiae.

99% of protein coding genes in humans have homologs in mice 99% of protein coding genes in humans have homologs in mice. And 80% are thought to be 1:1 homologs. From: http://www.macdevcenter.com/pub/a/mac/2004/06/29/bioinformatics.html

The Saccharomyces study could have also taken the comparative approach to gain insights into the functional similarities that defines the organisms as relatives. Recently 5 Campylobacter species’ genomes were sequenced, and analyzed to determine what is the core genetic blueprint of the genus (as well as differences between the species).

From: Fouts et al. 2005. PLoS Biology. 3(1):72-85.

Authors could have also taken a greater focus onto how the Campylobacter species evolved (or Saccharomyces). How each one evolved, and the steps by which they diverged from a common ancestor.

How did E. coli 0157:H7 evolve? From: Wick et al. 2005. Journal of Bacteriology. 187 (5)

What about the other “omics”? Genomics DNA (Gene) Functional Transcriptomics RNA Proteomics PROTEIN Metabolomics METABOLITE Transcription Translation Enzymatic reaction

From: Redfern et al. 2005. Journal of Chromatography B. 815:97-107

Downsides to the technique Genetic Drift - how can we tell what differences are really selection and important to organism function and not a result of genetic drift? Computationally intensive - large amounts of data that are being compared, still coming up with the tools to process and compare genomes. In order for the comparisons to be statistically relevant many more genomes will need to be sequenced.