April 9, 2007 | David F. Coppedge

Mutation Rate Catastrophe: You Can’t Even Break Even

In a tortoise-and-hare kind of story, a team of geneticists figured out what happens when positive natural selection tries to outrun mutations: “mutation rate catastrophe.”  Publishing in PNAS,1 they described how beneficial mutations might become established in a population rapidly (that’s the hare).  Eventually (this is the tortoise), harmful mutations accumulate to the tipping point, and the population goes extinct.
    The abstract begins with one of only two praises of natural selection (both qualified with reality checks):

The intricate adjustment of organisms to their environment demonstrates the effectiveness of natural selection.  But Darwin himself recognized that certain biological features could limit this effectiveness, features that generally reduce the efficiency of natural selection or yield suboptimal adaptation.  Genetic linkage is known to be one such feature, and here we show theoretically that it can introduce a more sinister flaw: when there is complete linkage between loci affecting fitness and loci affecting mutation rate, positive natural selection and recurrent mutation can drive mutation rates in an adapting population to intolerable levels.

The only other praise of natural selection was more of an insult.  Calling it robust does not help it jump the high hurdles their model revealed.  In a section called “How Genetic Linkage Can Subvert Natural Selection,” they spoke of it as a myopic fallen hero:

Our theoretical findings indicate that mutator hitchhiking can set in motion a self-reinforcing loss of replication fidelity, but the question of how a process as robust as natural selection could allow this to happen remains.  The key fact is that natural selection, although eminently robust, is a short-sighted process that favors traits with immediate fitness benefits.  The fitness cost of mutator hitchhiking is generally not anticipated because of the slow accumulation of deleterious load.  When a mutator hitchhikes with a new beneficial mutation, a simple model shows that the increased deleterious load due to the mutator is in fact suppressed during the spread of the beneficial mutation.  Indeed, the full fitness cost of the mutator is only realized well after the beneficial mutation has stopped spreading…. A mutator may therefore enjoy the immediate benefit of producing a new beneficial mutation without anticipating the eventual increase in deleterious load.  Because of this delay in the accumulation of deleterious load, natural selection can drive mutation rate up to the point of no return….

Indeed, their graphs all show that the temporary, wobbly rises of evolutionary progress under the best of conditions all come crashing down suddenly in the end.
    This particular study involved asexual, one-celled organisms.  It was not purely theoretical, though.  They stated that it is known that bad mutations “hitchhike” on the same genes with rare beneficial mutations.  Fatal mutations, of course, kill the organism right off, but some bad mutations delay their harm, adding to the mutational load over time.  Eventually, they catch up and, like the tortoise, win the race after the hare is pooped out.
    Why don’t the beneficial mutations ever win?  After all, they can spread rapidly in a population.  The reason is that fitness is short-sighted.  Natural selection cannot see down the road or have a goal.  It can only act on the immediate consequences of a change.  Harmful mutations, by contrast, are not necessarily weeded out immediately.  Consider, for instance, a slightly damaged proofreading enzyme.  It may not kill the organism right off the bat.  Give it time, though, and the damage will add up – right after the beneficial mutation has reached equilibrium in the population.  Their model shows that the mutation rate actually accelerates over time.  Surprisingly, it is the very process of adaptation for fitness that accelerates the mutation rate – not just in bacteria, but in higher organisms, too:

There is almost certainly no physiological barrier to such an effect in most organisms: the genomic mutation rate in organisms from viruses to eukaryotes is a quantitative trait affected by many mutations whose effects can readily cumulate to intolerable levels of error.  In what follows, we show that there need not be a selective barrier to this process either: because the full fitness effect of increased deleterious mutation takes some time to accumulate after a higher mutation rate has evolved, it is theoretically possible for a population to evolve a critically high mutation rate and subsequently go extinct.

The team tweaked the parameters of their mathematical model in various ways to try to get natural selection to make some headway.  They used infinite populations and small populations.  They used large and small genome sizes.  All efforts yielded the same result: negative mutations eventually swamped any gains from positive natural selection.  In cases of sustained “arms races,” like bacterial invaders vs. the immune system in mammals, the antagonists may struggle back and forth till both fall off the cliff.2  Surprisingly, the beneficial mutation itself may trigger the catastrophe.  Under equilibrium conditions, mutations tend to accumulate slowly, especially if some error correction mechanism is present.  A new beneficial mutation changes the rules.  Now, the population is adapting to a new situation, and the model shows that mutation rate rises to the occasion.
    In short, the population has no way to break even.  In a section called “Evolutionary Implications,” they wrote, “Our results suggest the possibility of a novel complement to existing explanations for why truly asexual populations are evolutionarily short-lived.”  Pick your poison: “Either an asexual population does not adapt and goes extinct as a result of the slow accumulation of deleterious mutations, as suggested by existing theory, or else it adapts and goes extinct as a result of the mutation-rate catastrophe.”
    How, then, could these authors, being evolutionists, keep faith in neo-Darwinian theory, which relies on mutation and natural selection?  Since their study concerned only asexual organisms, they assumed that early one-celled organisms quickly learned about this problem and adapted ways to get around it.  Maybe they invented proofreading.  Maybe they tried recombination.  Eventually, the idea goes, sexual reproduction arrived and helped mask the effects of “mutation rate catastrophe.”  But they freely admit this is all just speculation:

It is tempting to speculate that the mutation rate catastrophe phenomenon that we have observed here played a role in the early establishment of recombination in the most primitive life forms (41).  It seems probable that adaptation was continual in primordial populations and that only rudimentary mechanisms of genomic proofreading and repair had evolved, such that mutation rates were closer to intolerable values than they are in most present forms.  Under these circumstances, the mutation-rate catastrophe could have posed an imminent threat to any purely asexual population.

Nevertheless, they did not offer any detailed models of how the catastrophe could be avoided.  Other studies have denied that sexual reproduction offers any resistance to mutational load (10/12/2000, 05/16/2004).  The origin of sex has been called the “queen of evolutionary problems” (04/14/2003).  With 20 competing theories about what it’s good for, it would seem a hard sell that claim sex came to the rescue to prevent error catastrophe.
    These problems are not new.  Other evolutionists have written about “mutational meltdown” (12/14/2006).  Hermann Joseph Muller in 1932 described “Muller’s Ratchet,” a principle that shows mutations in asexual populations accumulate in an irreversible manner.  “Our findings depart from previous work, however,” they said, “by showing that such high mutation rates can be the catastrophic result of unfettered natural selection.
    Neo-Darwinian theory may suffer from this model, but there is one bright side for biomedical research.  Maybe pharmacists can take advantage of this finding and help pathogens to mutate themselves to death: “Our results suggest the interesting and related possibility that the adaptive immune response itself could drive a purely clonal pathogen to mutation rate catastrophe and extinction within the host.”  Locked in an arms race, the pathogen and the immune system can drive the germs over the cliff like a big buffalo jump.  “This mechanism could, in theory, help to explain the spontaneous clearance of some viral infections and suggests that recombination, which prevents runaway increases in mutation rate, may be essential to the persistence of other viral infections that are not cleared.”  Now you know why your cold or flu eventually clears up on its own.
    One final question: does recombination really prevent mutational catastrophe?  They did not discuss this “suggestion” in any detail.  They only assumed that it would.  Other studies reported here indicate that recombination, while it may stabilize the genome and aid genetic repair (07/18/2001, 07/31/2002), cannot add new genetic information (08/20/2003) and, at best, only delays the inevitable (10/19/2004, 12/14/2006)  Some recombinations, in fact, can be toxic (10/27/2005, bullet 3).  It would seem that adding another random influence in the mix would not overcome the “genetic entropy” of cumulative mutations.


1Philip J. Gerrish, Alexandre Colato, Alan S. Perelson, and Paul D. Sniegowski, “Evolution: Complete genetic linkage can subvert natural selection,” Proceedings of the National Academy of Sciences USA, 10.1073/pnas.0607280104, published online before print April 3, 2007.
2See the “Red Queen Effect” – i.e., running and getting nowhere, 09/07/2006.  The authors modeled the Red Queen Effect in the context of pathogen-immune arms races.  Their graph shows an upward adaptational fight ending in sudden collapse.

OK, how many times do we have to show that neo-Darwinism has been falsified for its disciples to throw in the towel?  (For a partial list, see 10/19/2004, 11/29/2004, and 12/14/2006).  Jason Wolf told us four years ago how indirect genetic effects produce “slippage on the treadmill” that hinders evolutionary progress (see 03/17/2003).  Now, this paper practically waxes the treadmill to a shiny, frictionless surface, complete with banana peel.  Think of it: neo-Darwinists have pinned their hopes on the rare, mythical “beneficial mutations” to generate novelty, and for natural selection to save every blessed tidbit in its sieve, leading to the wondrous variety of adapted life (wave the magic wand of millions of years here).  But now, their own mechanisms have turned on them.  Beneficial mutations (if there are such things) actually trigger a mutational arms race.  This subverts natural selection, begins a mutational meltdown, and sends the population off the cliff to extinction.  Charlie will never get endless forms most beautiful at this rate.
    He who has ears to hear, let him hear (04/06/2007).  If you have placed your eternal hopes on Charlie’s natural selection tale to win the cosmic lottery without responsibility to your Maker, then have faith.  You’re going to need a lot of it.

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Categories: Genetics

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