Transcript Lecture_14_2005

Comparative Genomics
What is Comparative Genomics?
It is the comparison of one genome to another.
Genomics
DNA (Gene)
Transcription
Transcriptomics
RNA
Translation
Functional
Genomics
Proteomics
PROTEIN
Enzymatic
reaction
Metabolomics
METABOLITE
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 genome to
inform us about the
entire organism.
Use information
from many
genomes to learn
more about the
individual genes.
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. 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.
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)
Transcription
Transcriptomics
RNA
Translation
Functional
Genomics
Proteomics
PROTEIN
Enzymatic
reaction
Metabolomics
METABOLITE
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.