Douglas D. Axe*
Biologic Institute, Redmond, Washington, USA
Abstract
Four decades ago, several scientists suggested that the impossibility of any evolutionary process sampling anything but a miniscule fraction of the possible protein sequences posed a problem for the evolution of new proteins. This potential problem—the sampling problem—was largely ignored, in part because those who raised it had to rely on guesswork to fill some key gaps in their understanding of proteins. The huge advances since that time call for a careful reassessment of the issue they raised. Focusing specifically on the origin of new protein folds, I argue here that the sampling problem remains. The difficulty stems from the fact that new protein functions, when analyzed at the level of new beneficial phenotypes, typically require multiple new protein folds, which in turn require long stretches of new protein sequence. Two conceivable ways for this not to pose an insurmountable barrier to Darwinian searches exist. One is that protein function might generally be largely indifferent to protein sequence. The other is that relatively simple manipulations of existing genes, such as shuffling of genetic modules, might be able to produce the necessary new folds. I argue that these ideas now stand at odds both with known principles of protein structure and with direct experimental evidence. If this is correct, the sampling problem is here to stay, and we should be looking well outside the Darwinian framework for an adequate explanation of fold origins.
Cite as: Axe DD (2010) The case against a Darwinian origin of protein folds. BIO-Complexity 2010(1):1-12. doi:10.5048/BIO-C.2010.1
Editor: Matti Leisola
Received: December 16, 2009; Accepted: March 23, 2010; Published: April 15, 2010
Copyright: © 2010 Axe. This open-access article is published under the terms of the Creative Commons Attribution License, which permits free distribution and reuse in derivative works provided the original author(s) and source are credited.
Notes: A Critique of this paper, when available, will be assigned doi:10.5048/BIO-C.2010.1.c. An early version of this paper (pre-peer review) is scheduled for publication in: Gordon BL, Dembski WA, eds. (2010) The Nature of Nature: Examining the Role of Naturalism in Science. ISI Books (Wilmington).
* Email: daxe@biologicinstitute.org
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