Evolutionary mechanisms part 3: the benefits of mutations

Mutations have an almost universally negative connotation (except in the context of superheros). When people hear the word, they instantly think of disabilities, bizarre disfigurements, and grotesque scenes from science fictions. The reality is, however, quite a bit different. Although there are extremely harmful mutations, they are actually in the minority, and mutations can be a wonderful thing. You see, mutations are the one and only way of generating truly new genetic information. In contrast, selection and genetic drift (two of the dominant evolutionary mechanisms) actually remove variation, and gene flow (the final mechanism) can only shuffle existing alleles among populations. So, without mutations there would be no variation, which means that there would be nothing for selection to act on, which means that populations would be unable to adapt to changes in the environment and would ultimately go extinct. To put it simply, for most species, sustained life on planet earth would not be possible without mutations.

Given how vital mutations are, it is important to have at least a basic understanding of them. Therefore, in this post, I am briefly going to explain why most mutations aren’t harmful and go over some of the different ways that they can create new genetic information.

What is a mutation?
First, I need to specify what I mean by “mutation.” Mutations are simply any changes in an organism’s DNA. They generally occur when a cell is replicating, and they can involve deleting bases, adding bases, or rearranging bases (remember, all DNA is made from combinations of four bases: adenine (A), guanine (G), cytosine (C), and thymine (T)).

We can group mutations into two broad categories (somatic and germline), but only germline mutations act as an evolution mechanism. Somatic mutations occur in body cells and do not get passed onto offspring. For example, if you frequently use a cancer coffin (aka tanning bed) you will likely mutate the DNA in your skin cells, ultimately resulting in skin cancer. That type of mutation is not, however, an evolutionary mechanism because it doesn’t change the allele frequencies of the population.

In order for a mutation to act as an evolutionary mechanism, it has to involve germ cells (eggs or sperm). Mutations in those cells will get passed onto the offspring, thus altering the gene frequencies of the population. So, when we talk about mutations as an evolutionary mechanism, we are only talking about germline mutations, not somatic mutations.

Note: you could argue that somatic mutations still alter gene frequencies because they may kill an individual, thus removing the individual’s alleles and altering the allele frequencies (cancer is a good example of this), but in that case, the mutation itself isn’t the mechanism, rather natural selection is the mechanism. In other words, it’s selection that actually removes the individual and modifies the allele frequencies, not the mutation.

Neutral and harmful mutations still cause evolution
It’s important to note that evolution is not inherently beneficial. Selection is always beneficial (for the immediate generation), but evolution itself is simply a change in allele frequencies, and there is no reason why that change has to be a beneficial one (indeed, genetic drift is generally bad). Therefore, all germline mutations that make it into the population represent evolutionary events, regardless of whether they are harmful, neutral, or beneficial.

Many mutations are neutral
It is an extremely common misconception that most mutations are harmful. In reality, for many species, most of them are essentially neutral (i.e., they do not benefit or harm the organism, and, therefore, selection does not act on them). For example, Nachman and Crowell (2000) estimated that for humans, only 1.7% of the mutations that occurred each generation were harmful; however, the number and nature of neutral vs. beneficial. vs. harmful mutations varies greatly among species (see Eyre-Walker et al. 2007 for a review).

There are several important reasons that many mutations are neutral. First, it is important to remember that mutations are completely random. There is no force controlling what mutations occur, and what an organism actually needs has no effect on what mutations will arise.

Second, the majority of organisms have large non-functional sections of DNA. In other words, there are big chunks of DNA that do not actually do anything (or at least do very little). The amount of DNA that is nonfunctional varies among species and is often debated. For example, there is significant controversy about how much of the human genome is actually functional, with estimates ranging from 8.2% (Rands et al. 2014) all the way to 80% (ENCODE Project Consortium) depending largely on how “function” is defined (you can find a brief discussion of the controversy here); however, regardless of the exact amount, everyone agrees that some portions of the genetic code don’t seem to do anything, which also means that mutations in those regions tend not to do anything.

The third reason has to do with the nature of proteins. DNA codes for amino acids, and amino acids string together to form proteins. Both the amino acids and the proteins are, however, redundant. Amino acids are formed by three bases, but the third base is usually irrelevant. For example, GAA, GAG, GAT, and GAC all code for the amino acid leucine. So a mutation that changes the third base will have no effect on the final protein. Further, proteins themselves are generally redundant, and there are multiple combinations of amino acids that will make the same protein.

Fourth, even if the protein itself is modified, that may not actually affect the organism. Indeed, all of the variation that you see in organisms is caused by mutations, and most of them are neutral. Why, for example, do only some people have attached earlobes, cleft chins, dimples, widow’s peaks, blue eyes, etc.? Quite simply, because at some point in the history of human evolution, mutations arose and spread through a population via genetic drift, ultimately resulting in variation for those traits; however, none of those traits affect an individuals ability to survive or reproduce. Things like the ability to curl your tongue like a taco don’t affect your evolutionary fitness, and are, therefore, neutral mutations. In reality, all of us are a massive collection of mutations.

Finally, remember that natural selection simply adapts populations for their current environment, so whether or not a mutation is beneficial will often depend on the environment and conditions that the organism is experiencing. For example, a mutation for bright red color may be very useful for a population in which females are selecting mates based on color, but that same mutation may be very harmful in a population in which individuals need to be camouflaged to avoid being eaten by predators.

Some mutations are beneficial
Some mutations are admittedly harmful, but selection eliminates or at least reduces them. Further, many mutations are beneficial, and selection can and does act on those, resulting in them increasing in frequency within the population.

Mutation accumulation experiments
There have been several excellent laboratory studies which have measured the formation and accumulation of beneficial mutations, and in many cases, the beneficial mutations arose more quickly than expected (Shaw et al. 2002, 2003; Joseph and Hall 2004; Perfeito et al. 2007; you can find a review and more detailed explication of these experiments in Halligan and Keightley 2009). In short, they put the study population under some experimental condition, then let the colonies do their thing for several generations. After the allotted number of generations, the researchers analyzed the colonies by comparing them to a control colony which was maintained in the ancestral condition. Thus, they could see the formation of new genetic information (i.e., mutations), and they could test whether or not the were beneficial by seeing if the mutated colonies grew and survived better than the originals. These studies very clearly demonstrate that beneficial mutations not only occur, but occur frequently enough to have adaptive significance. Therefore, if you honestly think that beneficial mutations don’t occur/are too rare for evolution, you are willfully ignorant of the facts.

Some creationists object to these studies by arguing that they were done in the lab, so we don’t actually know that beneficial mutations occur in nature, but this objection is completely invalid as it totally ignores the nature of mutations. The researchers generally don’t do anything to induce mutations. Rather, they simply put the organisms into a novel environment and let nature take it’s course. In other words, they aren’t constantly manipulation each generation. So, these studies are an excellent analog of nature, and there is absolutely no reason to think that they same processes don’t occur in nature. Remember, mutations are random. There is no mechanism that would cause beneficial mutations to spontaneously arise in a lab, but not in nature.

A mutation for HIV resistance in humans
In addition to the experimental studies, we also have evidence of the existence of beneficial mutations in humans. Perhaps most prominently, a deletion in the CKR5 gene results in resistance to HIV infections (Dean et al. 1996; Sullivan et al. 2001). This is very clearly a mutation (it is a deletion of several base pairs), yet it is also very clearly beneficial.

Bacteria evolve the ability to process citrate
There are many other examples of beneficial mutations that I could give (for example this really neat study describing a mutation that allowed blow flies to evolve pesticide resistance [Newcomb et al. 1997]), but I want to focus on just one final example. For all of the examples that I have given thus far, creationists typically respond with nonsense like, “those aren’t actually mutations, they are just part of the variation that God created when he made the earth.” This response is an ad hoc fallacy, it is logically inconsistent with the fact that creationists accept the results when identical methods show that some diseases are caused by mutations, and it doesn’t make any sense at all given that creationists believe that all modern animals evolved from the limited survivors of Noah’s flood (which would have had essentially no genetic variation). Nevertheless, let’s just say for sake of argument that creationists’ response was valid. This final example completely defeats that argument, because it is clearly and undeniably a beneficial mutation.

I am of course referring to the long term study of E. coli by Richard Lenski. He and his students did something amazingly clever. They started 12 bacterial colonies from an original clone, then watched them develop over thousands of generations. They didn’t interfere, they just let them do their thing, and eventually, something remarkable happened in one of the colonies. The bacteria were being grown on medium that included citrate, but E. coli is incapable of metabolizing (eating) citrate in the aerobic conditions under which they were being grown. Several thousand generations in, however, one colony suddenly became larger and began growing rapidly, and when the colony was examined, it was discovered that they had mutated the ability to consume citrate! Several lines of evidence demonstrate beyond the slightest shadow of a doubt that this was a mutation, not pre-existing variation. First, all 12 colonies were started from a single bacteria, so there was no variation. All of the bacteria were genetically identical at the start. In other words, if this trait was already present at the start of the experiment, it would have been in every bacteria in every colony from day 1, yet it only appeared in one colony, and it did not appear for thousands of generations. Further, the researchers saved and froze samples from each generation, so they were able to go back through them and pinpoint exactly when this mutation first arose (Blount et al. 2008).

You could not ask for a more clear or undeniable example of a beneficial mutation, but, unsurprisingly, creationists were not thrilled by this result. You can read the most famous exchange on this issue here. There is also a popular article on creation.com which takes issue with this result. I eventually plan on spending an entire post debunking their nonsense, but in short, they argue that this mutation still doesn’t explain the origins of new genetic material. However, as I will explain below, that response completely misses the point, and misrepresents how mutations actually work.

All mutations create new genetic information
Another very common misconception is that we don’t know of any mechanism for creating new genetic information. That claim is blatantly false, because mutations are, by definition, new genetic information. Some of them even work by very directly adding information. For example, some mutations are called “additions” and they are exactly what they sound like: they add extra bases to the DNA.

Other mutations don’t directly increase the amount of DNA, but they still add information. I think that this is where some of the confusion comes from: adding information does not necessarily mean making more DNA. Consider, for example, a mutation known as a substitution. This is where the wrong base gets used. So, for example, one section of DNA may have been supposed to be AGT, but instead a mutation happened and it ended up being CGT. Thus, the C was substituted for the A. In this case, we have not actually “added” genetic material, but we have still created new genetic material, because AGT and CGT will not produce the same amino acid.

Think of it this way. The DNA bases are like letters of an alphabet, and we string those letters together to form words (amino acids) and we combine words to form sentences (proteins). Now, consider the following sentence: “the dog ate the cats.” Imagine that a mistake (mutation) happened while copying that sentence so that the copy read, “the dog ate the bats.” All that happened was that one letter got substituted, but this sentence now tells us something totally different. It is new information, even though the number of letters hasn’t changed.

Further, some mutations (called deletions) actually remove DNA, but they still create new information. Let’s use the cat sentence again, but this time, suppose the that “s” got deleted, so the sentence became, “the dog at the cat.” This sentence is still different. Now we have one cat being eaten instead of several. It has a new meaning, even though it lost a letter. Even so, a mutation that removes a base will often result in an entirely new protein. Thus, new information is formed even though DNA is lost.

The mutation on the CKR5 gene that I mentioned earlier is a great example of this. The mutation actually deletes several bases, but that deletion results in a new code which ultimately results in resistance to HIV. So the loss of DNA actually creates new genetic information which results in a new and important function.

Conclusion
Despite the many myths about mutations (mostly perpetuated by creationists) mutations aren’t always harmful. Most of them are actually neutral, and beneficial ones do occur. Further, mutations are extremely important because they create new genetic information (even when they delete bases), and without mutations, there would be no variation, and evolution would grind to a halt. Ultimately, mutations are responsible for all of the variation that we see, and all of us are mutant freaks.

Other posts on evolutionary mechanisms:

Literature cited

Blount et al. 2008. Historical contingency and the evolution of a key innovation in an experimental population of Escherichia coli. Proceedings of the National Academy of Sciences 105:7899–7906.

Dean et al. 1996. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science 273:1856–1862.

ENCODE Project Consortium. 2012. An integrated encyclopedia of DNA elements in the human genome. Nature 48957–74.

Eyre-Walker et al. 2007. The distribution of fitness effects of new mutations. Nature Reviews Genetics 8:610–618.

Halligan and Keightley. 2009. Spontaneous mutation accumulation studies in evolutionary genetics. Annual Review of Ecology, Evolution, and Systematics 40:151–172.

Joseph and Hall. 2004. Spontaneous mutations in diploid Saccharomyces cerevisiae more beneficial than expected. Genetics 168:1817–1825.

Nachman and Crowell. 2000. Estimate of the mutation rate per nucleotide in humans. Genetics 156:297–304.

Newcomb et al. 1997. A single amino acid substitution converts a carboxylesterase to an organophosphorus hydrolase and confers insecticide resistance on a blowfly. Proceedings of the National Academy of Sciences 94:7464–7468.

Perfeito et al. 2007. Adaptive mutations in bacteria: high rate and small effects. Science 317:813–815.

Rands et al. 2014. 8.2% of the human genome is constrained: variation in rates of turnover across functional element classes in the human lineage. PLoS Genetics 10:e1004525.