Insights & Perspectives Commentary Comment on ‘‘Does constructive neutral evolution play an important role in the origin of cellular complexity?’’ DOI 10.1002/bies.201100010 W. Ford Doolittle1), Julius Lukesˇ 2), John M. Archibald1), Patrick J. Keeling3) and Michael W. Gray1)Ã Speijer [1] has provided a critique of suppresses the effect of this mutation, be fixed by selection operating within constructive neutral evolution (CNE) so that selection pressure is relaxed and populations of species – can neverthe- and its role in the origin and evolution the mutation may be harmlessly fixed by less be sufficiently advantageous to of cellular complexity [2, 3]. Not surpris- drift. Thus, A becomes dependent on B species (fostering enhanced speciation ingly, we disagree with his assertions. for its activity by virtue of the neutral, or reduced extinction rates) to spread by Because his description of the CNE ‘‘pre-suppressive’’ effect of the A:B species or clade selection. Eukaryotic model does not precisely conform to interaction. What we submit does not sex might be one of these. Introns could our view of CNE, as we [2, 4] and happen is that the mutation occurs first, be another. No one really thinks that the Stoltzfus [3] have elaborated it, we after which the interaction with B is insertion of introns was selected for at briefly re-state the model before positively selected for because it sup- the level of individuals – that is, that all addressing Speijer’s objections. presses the deleterious effect of the introns that are currently fixed within a The underlying premise of CNE is a mutation. species were fixed because individuals pre-existing, essentially neutral inter- Speijer’s ‘‘Think again’’ article [1] that bore them were at a selective action (RNA:RNA, RNA:protein, pro- embraces several misunderstandings advantage compared to conspecifics tein:protein) between component A, about this important process. First, we that lacked them. Indeed, for individ- which has some activity, and com- note that Speijer’s critique is considerably uals within species, intron addition ponent B. The activity of A is not longer than was our Perspective in could be slightly deleterious. It might dependent on the interaction with B, Science [3], giving him space to decon- nevertheless still be true that species nor is A’s activity negatively influenced struct several points that he may consider in which many introns have become by this interaction. Thus, B could dis- components or at least entailments of our fixed do better than species with few appear from the scene without any hypothesis, but that we would not. Let us introns (speciate more frequently or effect on the ‘‘fitness’’ of A. call these misunderstandings of Type A. become extinct less often), because We imagine that a mutation occurs Type B misunderstandings reflect introns facilitate exon shuffling or the in A that compromises its activity and Speijer’s conflation of micro- and mac- elaboration of multiple gene products that normally this mutation would be roevolution, or ‘‘levels of selection’’. He through alternative splicing. There eliminated from the population by puri- fails to recognize that some features that would thus come to be more intron- fying selection. However, the pre-exist- are neutral or even disadvantageous to bearing species (and in consequence ing interaction with B fortuitously individuals – and thus not expected to more introns) in the world, thanks to species selection. We see many CNE- established features as evolving like DOI 10.1002/bies.201100039 this, influencing however subtly the future evolutionary potential – the ‘‘evolv- 1) 3) Centre for Comparative Genomics and Department of Botany, University of British ability’’ – of species, and yet their initial Evolutionary Bioinformatics, Department of Columbia, Vancouver, British Columbia, Biochemistry and Molecular Biology, Canada establishment was the consequence of Dalhousie University, Halifax, Nova Scotia, the neutral ratchet we describe. Canada 2) Type C misunderstandings are of a Biology Centre, Institute of Parasitology, *Corresponding author: diverse sort. It seems simplest to Czech Academy of Sciences, and Faculty of Michael W. Gray Sciences, University of South Bohemia, Cˇ eske´ E-mail: [email protected] attempt to correct these as we read Bude˘ jovice (Budweis), Czech Republic Bioessays 33: 427–429,ß 2011 WILEY Periodicals, Inc. www.bioessays-journal.com 427 W. F. Doolittle et al. Insights & Perspectives ..... through Speijer’s essay, ending with a Speijer asserts, ‘‘Using ‘neutral’ theories Speijer then makes three arguable few general observations. to explain highly complex processes is claims. First he states that it is not very We do not recall that suppression by much less straight forward’’. We only likely that neutral changes will ‘‘take ‘‘remaining copies of the nonmutated partly concur. We would agree that over the complete population’’. Most gene’’ (Speijer’s Introduction) was part the case of single editing of a marsupial of the enterprise of molecular phyloge- of our model, nor indeed would we tRNA is ‘‘simple’’. Indeed it was aptly netics at the trans-species level is in fact think of that as a form of suppression. interpreted in CNE terms by the based on such neutral ‘‘takeovers’’. The Nor did we imagine that ‘‘reverse researchers who first described it, who neutral theory of molecular evolution mutation of the single first mutation also noted: ‘‘Because in other systems entails that no single pre-designated can not restore the original viable organ- many positions have become dependent neutral mutation is likely to be fixed; ism’’. It easily could do that, but if there on RNA editing subsequent to the initial at the same time it holds that some Commentary are additional sites at which further events, the initial mutations that have neutral mutations inevitably will be dependency (through mutation) is caused the evolutionary fixation of edit- fixed. Second, Speijer claims that we possible, then a random walk through ing are probably indiscernible today’’ assert categorically that reversal of dependency space will seldom end up [7]. But with an editing system that changes must be much less likely. back at the doorstep to independence – has already become essential for per- This is untrue: we assert only that when the initial condition. Similarly, even forming one edit, the conditions are in there are more open mutational paths to those who would vigorously deny that place for more to arise: it is actually the increased complexity than decreased life shows a tendency toward complex- first cut that is the deepest. complexity, complexity will most often ity would admit that since it began Speijer then invents three criteria for increase by chance. Third, he argues simply and since there are innumerable distinguishing CNE versus selection as that many neutral changes taken ways to become more complex, com- the cause of a complex feature: first that together can be detrimental, because plexity was inevitable. That is the kind there should be a ‘‘smooth’’ increase (no complexity incurs costs. This argument of ratchet we envision. Indeed, getting rapid bursts) in complexity, second that seems to be hiding some belief in opti- ‘‘stuck with it’’ is an appropriate catch- there should not be much variation mality, a quality that Speijer surely phrase, but otherwise we feel that between lineages in the extent of com- would not expect of that other prime Speijer is making a Type A mistake here. plexity, and third that there should not exemplar of a complex system evolved In Speijer’s representation of our be good adaptationist alternatives. The through both chance and necessity, model (Step 2) we are again baffled by first two criteria seem to us to be ad hoc human institutions such as universities. the invocation of ‘‘asymmetric div- in the extreme, and would certainly not There are reasons that we have else- isions’’, which does not form part of be our criteria. Of course such evolution where described CNE as a theory about the model in any of our papers that he will proceed by fits and starts. Similarly, ‘‘cellular bureaucracy’’ [2]. ‘‘Yes, Dr. cites. Of course if there are multiple we will all admit that the rare reinte- Pangloss, there is a downside to com- copies of the mutated gene, time will gration of a reverse transcript of a ma- plexity’’, we are tempted to say. be required for segregation: here the fact ture edited mRNA can wipe out a whole In considering The creative power of that such mutations are, in our model, slew of edits at once, resetting the clock. complexity as such, Speijer discusses rendered neutral by pre-suppression That this process might vary from line- two macromolecular machines, the means that this can happen. Maybe age to lineage seems a ‘‘no-brainer’’. ribosome and mitochondrial respiratory Speijer is confused by the phrase ‘‘dupli- The third criterion ignores the extensive complexes, that we mentioned [2] as cated information’’ in Lukesˇ et al. [5]. literature on the ease with which clever possible examples of CNE. Here, we We think gRNAs arise as duplicates of biologists can invent evolutionary ‘‘Just have space to comment only on the lat- the original gene, but are transcribed So Stories’’ [8], and is highly ‘‘verifica- ter example; elsewhere we will present from the opposite strand, producing a tionist’’. The principle behind this detailed CNE scenarios for the evolution complementary RNA. We think this is a criterion seems to be ‘‘better the widely of several other complex cellular Type A mistake on Speijer’s part. believed but unprovable hypothesis we machines. In Origin and use of cellular proc- have than an equally difficult-to-prove Speijer cites the electron transport esses, we feel that Speijer makes some but less popular alternative’’. chain complex I (ETC CI) as an example Type B mistakes.