Constructive Neutral Evolution (CNE)

Constructive Neutral Evolution (CNE) is a term that describes the evolution of complex systems by non-adaptive mechanisms. The idea (and the name) was developed by Arlin Soltzfus in 1999 (Stoltzfus, 1999) but it has antecedents in the literature and in the environment where Stoltzfus did his post-doc (Michael Gray and Ford Doolittle). It has been promoted by a number of prominent evolutionary biologists/population geneticists, notably Michael Lynch in his book The Origins of Genome architecture. Several examples have been described and discussed in the scientific literature and in popular books. For example, there is good reason to think that the evolution of the complex spliceosome that removes introns has evolved by mainly non-adaptive evolution.

Ford Doolittle and Michael Gray are fans of constructive neutral evolution. They and their collaborators wrote a review of the idea in Science (Gray et al., 2010). It has the provocative title "Irremediable Complexity." The same authors (different order) published another review the following year (Lukeš et al., 2011).

It's important to understand this concept because it challenges the idea that the evolution of complexity is adaptive and it sets the stage for challenging the idea that all adaptive structures arose exclusively by natural selection. Almost everyone who writes about constructive neutral evolution understands that it poses a problem for those who cling to adapatationist or selectionist views of evolution. It also helps us understand why the core idea behind irreducible complexity has been refuted.

Let's look at the introduction to the Lukeš et al. paper ...

In a recent Science Perspective, we highlighted a neutral evolutionary theory, called constructive neutral evolution (CNE) by Stoltzfus, emphasizing how such a process could lead to what we term ‘‘irremediable complexity’’: the seemingly gratuitous, indeed bewildering, complexity that typifies many cellular subsystems and molecular machines, particularly in eukaryotes. We offered (in fact reoffered) the CNE paradigm as a counterpoint to purely adaptationist/selectionist schemes that are often favored by biologists, and molecular biologists in particular, to explain the evolution of structural and biochemical complexity. We argued that continued failure to consider CNE alternatives impoverishes evolutionary discourse and, by oversimplification, actually makes us more vulnerable to critiques by antievolutionists, who like to see such complexity as ‘‘irreducible.’’ Here, we expand on this idea by presenting in more detail ‘‘case histories’’ that illustrate how CNE might have operated in the emergence of several complex systems, including RNA editing, the spliceosome, and the ribosome, and how it might be invoked more broadly as an evolutionary paradigm underlying cellular complexity in general.

They have a very nice figure that makes the whole idea quite easy to understand.¹

Imagine an enzyme "A" that catalyzes a biochemical reaction as a single polypeptide chain. This enzyme binds protein "B" by accident in one particular species. That is, there is an interaction between A and B through fortuitous mutations on the surface of the two proteins. (Such interactions are common as confirmed by protein interaction databases.) The new heterodimer (two different subunits) doesn't affect the activity of enzyme A. Since this interaction is neutral with respect to survival and reproduction, it could spread through the population by chance.

Over time, enzyme A might acquire additional mutations such that if the subunits were now separated the enzyme would no longer function (red dots). These mutations would be deleterious if there was no A + B complex but in the presence of such a complex the mutations are neutral and they could spread in the population by random genetic drift. Now protein B is necessary to suppress these new mutations making the heterodimer (A + B) irreducibly complex. Note that there was no selection for complexity—it happened by chance.

Further mutations might make the interaction more essential and make the two subunits more dependent on one another. This is a perfectly reasonable scenario for the evolution of irreducible complexity. Anyone who claims that the very existence of irreducibly complexity means that a structure could not have evolved is wrong.

The evolution of modern hemoglobin, composed of two alpha subunits and two beta subunits is an example of a well-known structure that probably evolved in this manner. We already know that a single subunit can function on its own because that's what myoglobin does.

It's important to note that this explanation for the evolution of hemoglobin has not been "proved" even though it seems extremely likely. Creationists will focus on this and claim that irreducible complexity is still a valid objection to naturalistic evolution. Their logic is faulty because the initial claim was that the very existence of irreducible complexity means that it could not possibly have evolved. That means, according to them, that all the intermediate steps had to be functional and evolution by natural selection can't accomplish the goal. In other words, they take the evolved complex (A-B) on the right of the figure above and point out that neither of the subunits has activity on its own therefore they both had to be created simultaneously in order to get activity. Evolution can't do this so gods have to take over.

All that's required is that evolutionary biologists propose a reasonable explanation making it possible for such structures to evolve naturally in a world where gods play no role in evolution. That has been done. The idea that irreducibly complex structures are impossible to evolve has been falsified.²

One of the characteristics of complex eukaryotes is that their enzymes and complexes are almost always a lot more complicated that the prokaryotic versions. It doesn't make sense that eukaryotic ribosomes, for example, have a lot more protein subunits than their bacterial counterparts.

If you understand Constructive Neutral Evolution, you will realize that there doesn't have to be an adaptive explanation for all this extra complexity. It can be easily explained by neutral evolution in small populations. This is especially true of mitochondrial ribosomes ...

When one looks at the ribosomes of mitochondria, however, what emerges is an entirely different picture, one of extraordinary evolutionary plasticity. In keeping with their endosymbiotic origin, mitochondrial ribosomes in some species have strikingly bacteria-like compositions. However, in other lineages, drastic changes to rRNA size and structure, as well as protein composition, have occurred. Most relevant here are cases where a marked reduction in the size of rRNA components has occurred concomitantly with a substantial increase in ribosomal protein complexity. For example, the human mitochondrial ribosome contains rRNA species that are about half the size of their bacterial counterparts, but the number of proteins has increased in both subunits to a complexity closer to that of cytoplasmic ribosomes. Clearly, the human mitochondrial ribosome has lost substantial RNA and gained substantial protein in the course of its evolution from a bacterial progenitor, reversing the usual protein:RNA ratio (33:67) to become protein-rich (69:310). An even more extreme situation is seen in the kinetoplastids. Here, rRNA shrinkage has resulted in Trypanosoma mitochondrial rRNAs of only 610 and 1,150 nucleotides, with additional proteins among a total of 133 (vs.55 in E. coli) evidently compensating for this loss. Notably, the novel mitoribosomal proteins do not have detectable homologs outside of the kinetoplastids, and only a low degree of conservation and/or divergent function within this lineage.

This process appears to have been accompanied by a substantial remodeling of ribosome structure. In the human mitochondrial ribosome, many proteins occupy new positions, and intersubunit bridges consist mainly of protein rather than RNA. Especially notable is the absence of 5S rRNA in the large subunit of the mammalian mitoribosome; instead, proteins occupy the site where this RNA species normally sits, suggesting that a protein element may assume some of the roles of 5S rRNA. An even more extreme situation developed in the RNA-poor mitoribosome of kinetoplastid flagellates, which is more porous than other known ribosomes and where functionally conserved sites, such as the mRNA channel, the transfer RNA passage, and the exit site for nascent polypeptides are occupied by newly acquired ribosomal proteins rather than familiar ones.

In short, a CNE scenario can be used to rationalize not only the emergence of the ribosome as an RNP per se but also its peculiar ‘‘degeneration’’ in certain systems, notably mitochondrial, where constraints on ribosome function are presumably limited only to synthesizing a very small number of proteins.

This view—neutral evolution of complexity—is not just a problem for creationists. Evolutionary biologists and other scientists need to change their way of thinking about evolution in order to adapt to the new emphasis on population genetics and the role of chance in evolution. Too many scientists see life's complexity as a finely tuned Swiss watch rather than a sloppy Rube Goldberg machine that's just good enough.

Here's Lukeš et al. again ... as you read this, think about your own view of complexity. Do you always interpret it as an adaptation for "fine tuning"?

As we pointed out previously, machines of marvelous complexity such as lightharvesting antennae in photosynthesis, RNA and DNA polymerases and their attending initiation, elongation, and termination complexes, apparatuses for import, folding, and degradation of proteins, or the cytoskeleton and its motors, all might have grown to their current form through a process of CNE accretion. The same argument could apply to large and complex regulatory networks, which are often described as being ‘‘finely tuned’’ but might be better interpreted as ‘‘runaway bureaucracy’’ or biological Rube Goldberg machines where what could be a relatively simple task is performed though many steps by an unnecessarily complex machine.

UPDATE: A reader has alerted me to a post by Dan Graur on the same subject (June 11, 2014): Rube Goldberg’s 131st Birthday: Irremediable Complexity by Constructive Neutral Evolution.

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1. Not that this is going to be much help to creationists. They are highly resistant to easy ideas.

2. The ideas described here have been around for twenty years and they have been explained repeatedly to many creationists, including all the leading figures in the Intelligent Design Creationist movement.

Gray, M.W., Lukeš, J., Archibald, J.M., Keeling, P.J., and Doolittle, W.F. (2010) "Irremediable complexity?" Science 330: 920-921. [doi: 10.1126/science.1198594]

Lukeš, J., Archibald, J.M., Keeling, P.J., Doolittle, W.F., and Gray, M.W. (2011) "How a neutral evolutionary ratchet can build cellular complexity." IUBMB life 63: 528-537. [PDF]

Stoltzfus, A. (1999) "On the possibility of constructive neutral evolution." J. Mol. Evol. 49: 169-181.