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.

  1. 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.
  2. 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.
  3. 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 below).

Community Phenotypes
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.

The origin 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 2004).

Functional Predictions based on Comparative Genomics
Genomic expression 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.
  • Cox-Foster 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.
  • D'Costa 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 2(9): 1386-1395.
  • Feder ME, Mitchell-Olds T (2003) Evolutionary and ecological functional genomics. Nature Reviews Genetics 4(8): 651-657.
  • Foerstner 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.
  • Hoekstra HE, Coyne JA (2007) The locus of evolution: Evo devo and the genetics of adaptation. Evolution 61: 995-1016.
  • Huynen MA, Snel B, van Noort V (2004) Comparative genomics for reliable protein-function prediction from genomic data. Trends in Genetics 20(8): 340-344.
  • King 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).
  • Landry 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.
  • Shaffer 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.
  • Taylor 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.
  • Whitham 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: 206-216.