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Ward and Kellis (Reports, September 5 2012) identify regulatory regions inthe human genome exhibiting lineage-specific constraint and estimate the extentof purifying selection. There is no statistical rationale for the examples theyhighlight, and their estimates of the fraction of the genome under constraintare biased by arbitrary designations of completely constrained regions.

Comment on "Evidence of Abundant and Purifying Selection in Humans for Recently Acquired Regulatory Functions"