Population Genetics Project #3

We spent quite a bit of time in lecture discussing polymorphisms at class I major histocompatibility complex loci in mammals. There is another class of peptides in mammals, $\alpha$-defensins, that are important in immune responses to bacteria, fungi, and enveloped viruses. In a recent paper, Lynn et al. [2] argue that certain amino acid residues in $\alpha$ defensins have been subject to positive selection, i.e., that selection favors nucleotide subtitutions causing an amino acid substitution. Your task is to provide a critical evaluation of this paper. In that evaluation, you'll want to address the following questions:

• Are the analytical methods used in the analysis powerful and appropriate? Are there approaches you might have used that they did not use?

• Is the authors' claim that ``methods that average substitution rates over all sites in a sequence have little power in detecting cases of positive selection'' accurate? Is an amino acid by amino acid analysis of selection always preferable to an average analysis across an entire peptide?

• What assumptions are embedded in the analyses that the authors use? How might these assumptions affect the conclusions they reach? Might they affect those conclusions in a way that should cause them to reach different conclusions than they do or at least to be more cautious about the conclusions they reach?

• What new insights are available, if any, over those provided by Hughes and Yeager [1] as a result of the new methodology that Lynn et al. [2] use?

• Based on the data summarized in Hughes and Yeager [1] and Lynn et al. [2], what are the major patterns of selection on nucleotide sequence variation in $\alpha$-defensins.

As described in the course overview, we're looking for a paper that's 4-5 pages long. Like Project #2, this one won't require a lot of data analysis. You may want to do some back of the envelope calculations to check the plausibility of what the authors assert, but we are not providing any data for you to analyse.¹ What this paper will require is that you critically analyze the assigned paper, assess whether the data are consistent with the conclusions drawn, and synthesize your critique into a defensible interpretation of the evolutionary history of $\alpha$-defensins in mammals. Your grade will be based on the sophistication and insight of your analysis of population genetic issues. You may find it relevant to discuss, briefly, certain experimental protocols, but that should be a minor component of your paper. We're interested in seeing how well you can apply population genetic principles to the interpretation of complex evolutionary phenomena, not on how much you can tell us about DNA extraction and sequencing. Don't worry if it seems that you'll need a little less than 4 pages or a little more than 5 pages to present your analysis. The page limit is intended primarily to suggest the level of detail we're expecting in the report. On the other hand, don't exceed 8 pages unless you check with Robynn or me first.