In DepthGenomics

Mysterious unchanging DNA finds a purpose in life

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Science  02 Jun 2017:
Vol. 356, Issue 6341, pp. 892
DOI: 10.1126/science.356.6341.892

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  • RE: Highly Conserved Sequences Need Not Encode Crucial Functions

    The piece on ultra conserved DNA elements (2 June, 2017, pg. 892) falls into the logical fallacy that the precision of conservation tells you something about the importance of the sequence (“UCEs presumably had some crucial function”). Not true, but I know the trap because I’ve been there. I’m afraid I can’t remember which visitor to my lab disabused me, but precise conservation tells us only that every base pair is subject to selection, nothing about the strength of that selection (beyond a modest minimum). The near neutral theory of molecular evolution tells us that selection wins over mutation and drift roughly when the selective advantage is greater than the inverse of the effective population size (1). For example, with an effective population of 10,000, a selective differential of just 0.01% would maintain the status quo. In the same vein, when small differences in brain structure were noted, we read that “although differences may be too small to be significant for … lab mice, they might be catastrophic … in the wild”. Wrong again. My lab showed some years ago that gene knockouts in yeast that have no phenotype detectable by conventional criteria are at a selective disadvantage more than adequate to maintain function in the face of mutation and drift even under “coddled” lab conditions (rich medium) (2). In other words, there is no need to invoke conditional selection under stress. The same likely is true of the targeted mutations in UCEs.

    Competing Interests: None declared.