all classes of elements (RNA and regulatory) show depressed derived allele frequencies, consistent with recent negative selection occurring in at least some of these regions (Figure 1E). An alternative approach examining sequences that are not clearly under pan-mammalian constraint showed a similar result (Luke Ward and Manolis Kellis, personal communication). This suggests that an appreciable proportion of the unconstrained elements are lineage specific elements required for organismal function, consistent with long standing views of recent evolution56, and the remainder are likely to be “neutral” elements2 which are not currently under selection, but may still affect cellular or larger scale phenotypes without an effect on fitness.
