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Sunday 20 April 2008

To Mutate or not to Mutate: That is NOT the Question

Since my formal biology education consisted of a single high school course, my understanding of biology is somewhat sketchy. So, like most Christians examining evolution, understanding the evidence can sometimes be a difficult slog, particularly when the direction the evidence is pointing seems counter intuitive.

Take, for example, genetic mutations. Aren’t beneficial mutations too rare to account for the development of life through natural selection? Wouldn’t harmful mutations, at a minimum, counteract the good mutations? These are (the semi-rhetorical) questions that are asked frequently, particularly by those who wish to discredit the theory of evolution. And really, I don’t think I could have provided a succinct answer to these questions (or even pointed out that the questions themselves betray a misunderstanding of how natural selection and genetic mutations interact).

Maybe I can now. I recently encountered, almost simultaneously, 2 independent and simple explanations for the ability of helpful mutations to influence adaptation. For me, simple explanations are better. And since even simple doesn’t always seem to work, two simple explanations are twice as good.

The first explanation comes from Daryl Domning in his book Original Selfishness: Original Sin and Evil in the Light of Evolution. In his section on “Objections to the Darwinian View of Nature”, Domning addresses the question of the rarity of “favorable” mutations.

When a mutation is first exposed to selection, it may be selectively neutral (hence not eliminated), and only become favorable when circumstances change. Therefore the “window” of time within which an ultimately favorable mutation has to occur before it is needed may actually be quite generous. (page 37)
In other words, these favorable mutations do not need to strike while the iron is hot. They can “wait” for a long, long time before affecting the course of evolution.

The second explanation comes from Stephen Matheson in his post Mutations, Selection, and Bacteria. Matheson first points out that the ratio of harmful to helpful mutations has been grossly overestimated. Secondly, although harmful mutations may be bad for an individual organism, they are not necessarily bad for a population. But the key point (for me anyways) was his comparison of two definitions for the process of adaptation. The first (inaccurate) definition is as follows:

Adaptive evolution occurs when natural selection favors certain mutations which are beneficial as opposed to harmful. When new challenges arise, new adaptations arise as new beneficial mutations are generated and selection favors these mutations.
The implication here is that new mutations occur “just in time” like parts in an efficient Japanese auto factory. But, as Domning points out above, that is just not necessary. (And anyways, whoever said evolution was efficient?). As Matheson states, referring to the recent book Edge of Evolution by ID proponent Michael Behe:

[The] whole silly book is based on calculations that assume that new mutations must be generated, simultaneously, after the introduction of the new challenge.
Mutating is not a strategy used by populations to address challenges. The occurrence of mutations is independent from a population’s environment. This is the random part of evolution. However, as the environment changes, so too the potential “usefulness” of the variation caused by a random mutation. Only then can one know whether a mutation was “useful” or not.

The second (much more accurate) definition for the process of adaptation is as follows:
Adaptive evolution occurs when natural selection favors previously-existing genetic combinations that are more fit than others. When new challenges arise, new adaptations arise as selection favors individuals whose genetic endowments are best suited to the new challenges.
Natural selection does not act on mutations themselves, but on the variation caused by mutations.

Ok. If I was on a stage debating hucksters like Hovind, Safarti, or Ham, I’d probably badly mangle the argument and lose the debate. (Um, could I have a 30-minute time-out while I research that question please?) But at least I feel like I understand how the process of adaptation works, and why the arguments of anti-evolutionists are so badly flawed.

11 comments:

RBH said...

There's another way to analogize the views you've described. What constitutes a "beneficial" mutation depends, as you've said, on the selective environment. All else equal, in a relatively stable environment to which a population is pretty well adapted, a lower proportion of mutations (or pre-existing genetic combinations) will be immediately "beneficial." A useful analogy is a nearly-focused microscope. If a microscope is fairly close to being well focused, most random (in direction and magnitude) tweaks of the focusing knob will be deleterious -- they'll either move the 'scope further away from focus or will overshoot the focus point to become unfocused on the other side of 'perfect' focus. The further the original setting is from optimal focus, the greater the proportion of tweaks (defined as above) will be "beneficial."

That analogy has some disabilities, of course, most notably that the single microscope has to be imagined as a slew of microscopes with some distribution of 'goodness-of-focus' that has a mean nearer to (or further from) the optimal focus point. In addition, it doesn't explicitly refer to the length of the temporal window for assessing the effect of variations. But it's not too misleading. :)

Mike Beidler said...

Steve,

Great post! I, too, don't consider myself a biologist by any stretch of the imagination, but I can't help but realize how wrong I've been about the mechanisms of natural selection ever since I began reading up on the subject.

All that YEC literature out there blasting evolution contains oversimplfications, purposeful obfuscations, and outright misunderstandings of evolutionary theory. It's too bad Christians in general don't unsubscribe to ICR's Acts & Facts and read outstanding works like Domning's book (which is in my "Creation of an Evolutionist" Amazon.com estore) and Fairbanks' Relics of Eden. If they did that, Christianity might just have a broader impact on society at large instead of bolstering its pseudo-scientific charicature.

Anonymous said...

Great website. I will check it out more often. You are a courageous man :)

Bill Ather said...

Okay, as another person whose biology background is woefully insufficient, let me ask the follow-up question: what properties of DNA make neutral mutations feasible? Presumably (but I'd love to be corrected by someone in the know) it is because not all DNA sequences actually encode genetic information. In an information-bearing system in which every element DOES encode information (like this message), NO alteration in the elements can be "neutral". Let's try it by changing one element in this sentence. Let's try xt by changing one element in this sentence. Hm, that was deleterious. ANY change will either yield nonsense or an unintended alternation in meaning. Presumably DNA doesn't work like this because only parts of it actually code for gene production. Am I right?

And, of course, this yields another question. A change in DNA can't lead directly to the generation of a new and different protein without corresponding changes in the messenger RNA, can it? Is changing DNA sufficient to change what is actualized or instantiated at the protein level?

You can see that I'm totally ignorant of these underlying mechanics, which really are at the heart of the issue. Of course I could just take a relevant class, but as long as admitting ignorance and hoping for some instant enlightenment is allowable here, I thought, "Why not?"

RBH said...

I'll take a shot at Bill Ather's questions.

... what properties of DNA make neutral mutations feasible? Presumably (but I'd love to be corrected by someone in the know) it is because not all DNA sequences actually encode genetic information. In an information-bearing system in which every element DOES encode information (like this message), NO alteration in the elements can be "neutral". Let's try it by changing one element in this sentence. Let's try xt by changing one element in this sentence. Hm, that was deleterious. ANY change will either yield nonsense or an unintended alternation in meaning. Presumably DNA doesn't work like this because only parts of it actually code for gene production. Am I right?

Several properties of the system make neutral mutations possible. First, recall that "neutral" means that the phenotype (organism) that is produced (from the genetic information via a complex developmental process) has no differential reproductive fitness -- "neutral" refers to the selective effect on the phenotype. That is, "neutrality" is not a property of the DNA or alterations in it, it is a property of the organism. So any mutation that produces a phenotype that is not more (or less) reproductively successful (on average) is neutral.

Second, there is redundancy in the DNA system. There are 64 combinations of the four bases possible in the triplets that are the basic "code" of the system. (Bear in mind that "code" is a metaphor here. We're talking about chemical processes, not symbolic processes.) A given amino acid (component of a protein) may be produced by several different triplets of bases. For example, UUU and UUC both code for Phenylalnine. So a substitution mutation that changes UUU to UUC is neutral, since the same amino acid -- Phenylalanine -- will be produced regardless of whether U or C is in the third position. Similarly, UUA and UUG code for Leucine and a change from A to G in the third position will be neutral. The 'standard' genetic code is here.

Third, developmental processes are often fairly robust with respect to the phenotype produced from a given genetic combination. That is, developmental constraints tend to 'canalize' the development of the reproducing organism from the egg, so that variations in the DNA do not necessarily translate into (selectively relevant) variations in the phenotype. Here is an example of the kind of research on this topic that's going on.

There's more to the story, but those factors alone illustrate how selectively neutral phenotypic effects can be produced by mutations of genes.

Finally, beware of the language analogy to DNA. The genetic material in a fertilized egg is not a blueprint for an adult organism; it is more like a recipe for building an organism via developmental processes interacting with the environment of the developing organism.

Bill asked further

And, of course, this yields another question. A change in DNA can't lead directly to the generation of a new and different protein without corresponding changes in the messenger RNA, can it? Is changing DNA sufficient to change what is actualized or instantiated at the protein level?

Yes, changing the DNA is sufficient to change what is actualized at the protein level, subject to the redundancies described above. mRNA is transcribed from DNA by a purely chemical process, so the sequence of bases of the mRNA depends solely on the DNA for its structure. mRNA is not an independent factor. mRNA is translated, again by a purely chemical process, into the sequences of amino acids that are proteins.

Recall also that a large amount of variation in phenotypes is not due to differences in protein-coding DNA itself, but is due to differences in the regulation of expression of protein-coding DNA. Here's Wikipedia's overview.

I hope that helps.

Peter Parslow said...

Bill,
making an analogy between the DNA / genome collection of a species and the contents of a single sentence misses some things; in particular, that a population contains a variety of genetic codes, which are "neutral" at that point in time.

For example, I have blue eyes, you may have brown eyes. Some time in the future, the environment may favour one sufficiently that the human race adapts to all have the same coloured eyes.

If you need a linguistic analogy, perhaps it is that some time ago the two phrases "I feel happy" and "I feel gay" meant the same. Now the environment has changed, and one of them may no longer be in "perfect focus".

Bill Ather said...

rbh and peter, thanks much. One thing I like about this site is that it's permissible to ask "stupid" (i.e., uninformed) questions as long as one admits one's ignorance in advance. You'd be surprised (or maybe not?) to discover how hard it is to find a forum with that property. Ignorance isn't supposed to be a crime, but often it's treated as one.

Thanks for helping me get an overview of what this is really all about. Digesting this material in depth will be even more interesting than watching reruns of MacGyver!

Steve Martin said...

RBH: Thanks for the helpful analogy. And no, I’m not going to insist that your analogies be inerrant :-).

Mike: You are right. It doesn’t take long for us non-specialists to read “both sides” and see that the anti-evolutionary literature is full of lousy arguments. But recognizing a bad argument (and pointing out the deficiencies) is much easier than actually articulating a good argument. That is why I tend to avoid detailed scientific analysis on my blog & leave it to guys like Matheson who actually understand the details and can explain it in relatively simple terms for the rest of us.

Evedyahu: Welcome. On being courageous – maybe not. As I noted in my welcome post (http://evanevodialogue.blogspot.com/2007/05/welcome-to-dialogue.html)

[I didn’t think too much about evolution] until a few years ago when it became obvious that my 9-year old son was starting to have questions about science and faith, questions I myself had faced when I was younger but was maybe too afraid to discuss, or to investigate too deeply. Thus started a quest to investigate "the truth" of evolution and its implication for my faith. Sometimes courage to face our fears comes not because we are courageous, but because the alternative is deemed even worse.


Bill: Thanks for the potential heart attack – go ahead ask me any question on biology you like :-) . Actually, any and all questions are allowed. No commitment that the blog owner will have the foggiest idea of an answer though and I can’t commit to anyone else here answering it either. On your specific question I believe I had “a very foggy idea” but was going to suggest you ask your question over at Stephen Matheson’s site that I quoted in my post. If you haven’t seen this site yet, I highly recommend adding it to your blog reader.

RBH, and Peter: Thanks for the replies to Bill. Medals of honour (Canadian / British spelling only) for both of you for preventing above said heart attack.

Anonymous said...

It's probably worth pointing out, too, that not all evolution is adaptive. It is possible for phenotypic change to accumulate in a lineage that neither benefits nor harms the organisms that express it. Later, these changes may become beneficial and exapted by natural selection.
There's a whole slew of peer-reviewed literature on this subject. A good start would be Gould and Lewontin's "Spandrels" paper:

http://www.aaas.org/spp/dser/03_Areas/evolution/perspectives/Gould_Lewontin_1979.shtml

Stephen Matheson said...

RBH did a great job. Here's some more illumination.

Mutations can be neutral in various ways: as RBH notes, some "silent" mutations (within genes) change the DNA sequence without affecting the amino acid sequence of the encoded protein. These are mutations that are neutral (usually) in nearly every way. Other mutations change the amino acid sequence of the protein, but have no significant effect on the protein's function. Other mutations change the amino acid sequence of the protein, and alter its function, but have no significant effect on the organism. And some affect the organism noticeably, but don't affect the organism's fitness.

All of the above can apply to mutations that occur outside of genes, in non-coding DNA: mutations can be completely irrelevant, or can alter gene expression without affecting the organism, or can alter the organism without affecting fitness.

Think about it: how could organisms (including humans) differ from each other (i.e., display genetic diversity) if it were not possible for genetic changes to frequently be neutral in their effects?

RBH said...

Thanks for the amplification, Prof. Matheson.

I'll add that the Berkeley site Understanding Evolution is an excellent resource for people just beginning their exploration of biological evolution.