Comparative Functional Genomics
An exploration of current research that pairs both genomic techniques
and bioinformatics approaches with ecologically and evolutionarily interesting
questions often (but not always) using organisms that are not the traditional
models in biomedical science.
For the first week
everyone will read the introduction to the symposium on Ecological Genomics
that took place at the Canadian Society for Ecology and Evolution held
at the University of Toronto in May 2007 (Landry and Aubin-Horth, 2007)
as well as the review article that really kick-started the field of Evolutionary
and Ecological Genomics in 2004 (Feder and Mitchell-Olds 2003). Using key
terms, or cited authors in these two publications each student will find
one primary research paper of personal interest. The subject of your chosen
papers will be the starting point for our conversation to begin to discuss
the scope of the field and outline our general areas of interest for the
remainder of the semester. The chosen papers are not necessarily those
that will be presented formally throughout the semester.
Each two hour seminar session will be lead
by a team of 2-3 students and each student will be involved in 2 teams
over the duration of the course. The team leader will select the topic
choosing 1 review paper and one research paper. These papers will be posted
on the courses server one week before discussion. The team is expected
to work together.
- The team leader will present “what’s
what” on this topic; what is the history, what is the goal, and
what are the major findings.
- A second student will explore the methods and
techniques in greater detail and present an explanation of “How to”.
This may include laboratory or computational techniques that are used
in the research paper.
- A third student (or one of the above) will introduce
the topic that day with “who’s who”. This brief presentation
will focus on one of the paper authors and will include the educational
and employment background, previous publications and awards, activities
outside of science, summary of graduate student and postdoc topics in
that research group. (this is meant to be fun)
Possible topics include (find links to referenced papers
It seems clear, from studies of two-species interaction that heritable
traits in a single species will affect another species. The extent to which
these effects filter through the entire ecosystem can hardly be imagined.
However, description of these interactions is the goal of "ecosystem
genomics" (Whitham et al. 2006; Wade 2007).
The Genomics of Gene Expression
The new technique of eQTL attempts to marry gene expression profiling by
microarray with genetic mapping of quantitative trait analysis (Stamatoyannopoulos
2004; Gibson and Weir 2005). While this approach has met with its greatest
success in Drosophila (e.g. (Edwards et al. 2006) and other model organisms
it holds great promise for the analysis of complex phenotypes.
of new genes
Gene duplication has generally been viewed as a necessary
source of material for the origin of evolutionary novelties (thoroughly
reviewed by (Taylor and Raes 2004), while notable functional duplication
examples abound in organisms ranging from fish to humans (e.g.(Chen et
al. 1997);(Perry et al. 2007), comparative functional genomics now offers
a genome wide approach to trace the evolutionary fate and consequences
of duplicated genes (Lynch and Conery 2000).
What “types” of
mutations underlie “adaptation”?
Long before the full genome
sequence projects, in their highly influential paper, King and Wilson (1975)
argued that the modest degree of divergence in protein sequence couldn't
account for profound phenotypic differences observed between humans and
chimpanzees. Empirical evidence now supports the importance of "cis-regulatory
mutations" (Wray 2007). However others argue that this preponderance
of regulatory rather than structural may be skewed by the research techniques
(Hoekstra and Coyne 2007)
Evolution of Gene Expression
The portion of phenotypic
diversity that is generated through changes in gene regulation. is poorly
understood with regard to principles that drive its evolution. Comparative
research between strains of yeast, species of Drosophila and "mutation
accumulation lines" has begun to yield some insight (Snel and Huynen
Functional Predictions based on Comparative Genomics
data provide tell us much about what proteins are deployed when, and other
techniques allow us to know what proteins interact with each other. However
this noisy data does not give a clear picture of the true function for
many genes. If the overlap in information among various genomics datasets
from various techniques are taken into account, one observes an increase
in the reliability of the protein-function predictions (Huynen et al. 2004).
Drosophila Comparative Genomics
Next to the pea plant, Drosophila melanogaster has the longest history as the model organism for genetic analysis of phenotype,
development and physiology. Accordingly, Drosophila melanoagster (joined
by C. elegans) was at the front of the genomic era. Now, with the additional
genomic sequence for 11 more Drosophila species, this model organism is
poised to make significant contributions outside the lab in the areas of
ecology and evolutionary genomics .
Metagenomics or Environmental Sequencing
While the most newsworthy advances allowed by "Next-Generation Sequencing" techniques
(reveiw by (Shaffer 2007), primer by Chi, 2008; (Foerstner et al. 2006)
involve model organism with fully sequenced genomes, this new technology
also allows for the advance of "metagenomics" also known as "Environmental
Sequencing" in practical applications such as multi-drug resistance
in bacteria (D'Costa et al. 2007) and colony collapse in honey bees (Cox-Foster
et al. 2007).
- Chen LB, DeVries AL, Cheng CHC (1997) Evolution of antifreeze
glycoprotein gene from a trypsinogen gene in Antarctic notothenioid fish.
Proceedings of the National Academy of Sciences of the United States
of America 94(8): 3811-3816. (not a comparative genomics topic)
- Clark AG,
Eisen MB, Smith DR, Bergman CM, Oliver B et al. (2007) Evolution
of genes and genomes on the Drosophila phylogeny. Nature 450(7167): 203-218.
DL, Conlan S, Holmes EC, Palacios G, Evans JD et al. (2007) A metagenomic survey of microbes in honey bee
colony collapse disorder. Science 318(5848): 283-287.
VM, Griffiths E, Wright GD (2007) Expanding the soil antibiotic resistome: exploring
environmental diversity. Current Opinion in Microbiology 10(5): 481-489.
- Edwards AC,
Rollmann SM, Morgan TJ, Mackay TFC (2006) Quantitative
genomics of aggressive behavior in Drosophila melanogaster. Plos Genetics
ME, Mitchell-Olds T (2003) Evolutionary and ecological
functional genomics. Nature Reviews Genetics 4(8): 651-657.
KU, von Mering C, Bork P (2006) Comparative analysis of environmental sequences:
potential and challenges. Philosophical Transactions of the Royal Society
B-Biological Sciences 361(1467): 519-523.
- Gibson G,
Weir B (2005) The quantitative
genetics of transcription. Trends in Genetics 21(11): 616-623.
HE, Coyne JA (2007) The locus of evolution: Evo devo and the genetics
of adaptation. Evolution 61: 995-1016.
MA, Snel B, van Noort V (2004)
Comparative genomics for reliable protein-function prediction from genomic
data. Trends in Genetics 20(8): 340-344.
MC, Wilson AC (1975) Evolution at 2 Levels in Humans and Chimpanzees.
Science 188(4184): 107-116. (not comparative functional genomics but
a classic paper everyone should read at some point).
CR, Aubin-Horth N (2007)
Ecological annotation of genes and genomes through ecological genomics.
Molecular Ecology 16: 4419-4421.
- Perry GH, Dominy NJ, Claw KG, Lee AS,
Fiegler H et al. (2007) Diet and the evolution of human amylase gene
copy number variation. Nature Genetics 39(10): 1256-1260.
C (2007) Next-generation
sequencing outpaces expectations. Nature Biotechnology 25(2): 149-149.
- Snel B, Huynen MA (2004) Quantifying modularity in the evolution of
biomolecular systems. Genome Research 14(3): 391-397.
- Stamatoyannopoulos JA (2004) The
genomics of gene expression. Genomics 84(3): 449-457. (not
currently available, I'm working on it)
- Stark A,
Lin MF, Kheradpour P, Pedersen JS, Parts L et al. (2007) Discovery
of functional elements in 12 Drosophila genomes using evolutionary signatures.
Nature 450(7167): 219-232.
JS, Raes J (2004) Duplication and divergence: The evolution of new genes and old
ideas. Annual Review of Genetics 38: 615-643.
- Wade MJ (2007) The co-evolutionary
genetics of ecological communities. Nature Reviews Genetics 8(3): 185-195.
TG, Bailey JK, Schweitzer JA, Shuster SM, Bangert RK et al. (2006) A framework for community and ecosystem genetics: from genes to
ecosystems. Nature Reviews Genetics 7(7): 510-523.
- Wray GA (2007) The evolutionary
significance of cis-regulatory mutations. Nature Reviews Genetics 8: