Specified Complexity (notes)

A Review Of The Case Against A Darwinian Origin Of Protein Folds By Douglas Axe, Bio-Complexity, Issue 1, pp. 1-12

By Robert Deyes  ARN Correspondent


In his latest critique Biologic Institute molecular biologist Douglas Axe has raised the ever-pertinent question of whether Darwinian evolution can adequately explain the origins of protein structure folds given the vast search space of possible protein sequence combinations that exist for moderately large proteins, say 300 amino acids in length. To begin Axe introduces his readers to the sampling problem. That is, given the postulated maximum number of distinct physical events that could have occurred since the universe began (10exp150) we cannot surmise that evolution has had enough time to find the 10exp390 possible amino-acid combinations of a 300 amino acid long protein.


The battle cry often heard in response to this apparently insurmountable barricade is that even though probabilistic resources would not allow a blind search to stumble upon any given protein sequence, the chances of finding a particular protein function might be considerably better. Countering such a facile dismissal of reality, we find that proteins must meet very stringent sequence requirements if a given function is to be attained. And size is important. We find that enzymes, for example, are large in comparison to their substrates. Protein structuralists have demonstrably asserted that size is crucial for assuring the stability of protein architecture.

The Case Against a Darwinian Origin of Protein Folds

Douglas Axe

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.

http://bio-complexity.org/ojs/index.php/main/article/view/BIO-C.2010.1