New from Science Daily:

“Across species from fish to mammals, they [researchers of this study] found that rates of protein evolution showed the same body size and temperature dependence as metabolic rate. Specifically, their mathematical model predicts that a 10-degree increase in temperature across species leads to about a 300 percent increase in the evolutionary rate of proteins, while a tenfold decrease in body size leads to about a 200 percent increase in evolutionary rates.”

From these results the authors conclude that “rates of protein evolution are largely controlled by mutation rates, which in turn are strongly influenced by individual metabolic rate.” It is well known that many physiological characteristics and population density correlate with metabolic rate (e.g. body size and relative metabolic rate). Now I suppose we can add this correlation to the list.

It appears the authors have observed something intuitive and subtly ground-shaking: the operation of an organism’s metabolism can influence the rate of introduction of mutations into that individual. This suggests that the dynamics of cellular metabolism, which are encoded in the genome and altered through evolutionary history, can in some way set the rate of change of the genome itself1. By no means does this suggest or implicate behavior in controlling such introduction, rather the idea that through history, genomes have been able to take a more active role in buffering against probably deleterious changes to itself, via the construct of a metabolism encoded by the genome.

Unfortunately the authors decided to focus on the significance of spontaneous mutation in being the driving force of protein evolution, rather than the ability of the organism (with its genome altered through its species’ historical interactions with the environment) to influence this mutation rate.

So let’s try to parse what the authors of the paper say in their abstract.

“Since the modern evolutionary synthesis was first proposed early in the twentieth century, attention has focused on assessing the relative contribution of mutation versus natural selection on protein evolution.

Yes, this is a fundamental issue that still leads to much discussion and controversy (e.g. Michael Lynch’s paper, “The frailty of adaptive hypotheses for the origins of organismal complexity, PNAS 2007”), and there is yet no clear answer except that both forces play a significant role.

“Here we test a model that yields general quantitative predictions on rates of protein evolution by combining principles of individual energetics with Kimura’s neutral theory. The model successfully predicts much of the heterogeneity in rates of protein evolution for diverse eukaryotes (i.e. fishes, amphibians, reptiles, birds, mammals) from different thermal environments. Data also show that the ratio of non-synonymous to synonymous nucleotide substitution is independent of body size, and thus presumably of effective population size.”

These are their major results. They found a correlation between protein evolution and metabolic rate that is independent of natural selection. Since metabolic rate also correlates with body size, one might expect dn/ds ratios to correlate with body size if selection did play a role (since the dn/ds ratio is used to describe the force of natural selection in a protein coding sequence). Also since body size correlates inversely with population size (more properly, population density), presumably dn/ds ratios are also independent of population size.

“These findings indicate that rates of protein evolution are largely controlled by mutation rates, which in turn are strongly influenced by individual metabolic rate.”

If dn/ds ratios are also independent of population size, then protein evolution is independent of neutral drift. So the only other possible evolutionary forces driving protein evolution rate are either mutation or draft. (The force of mutation is also dependent on population size, but is also determined by the rate of spontaneous mutation. At the moment, I am not qualified to discuss the relevance of draft.)

(A brief aside… The force of selection depends on the relative fitness of a trait as well as the population size. A population may ‘feel’ the force of selection on a trait if the fitness coefficient is greater than about 1/2N, half of the inverse of population size. This is because, on the other hand, the force of neutral drift operates to remove the genetic variation seen by selection, and is thus also dependent on population size. The basic idea is that selection has a powerful effect on large populations such as bacteria, but smaller effect on humans.)

Thus since dn/ds ratios are independent of body size, the authors conclude that the rate of incorporation of mutation has a detectable and significant effect on the rate of protein evolution. Also since rate of protein evolution correlates with metabolic rate, then the mutation rate is “strongly influenced” by metabolic rate. i.e., the operation of an individual organism’s metabolism can influence the rate of introduction of genetic mutations.

If a physiological process such as metabolism influences the rate of evolution in a species, this suggests that the historical evolution of that species is partly responsible for its current mutation rate. Evolution itself occurs as the result of a population’s interaction with the environment, without which there is no mutation and no change. Thus the interaction of some genotope with its past environments creates an auto-regulatory structure (e.g. metabolism) through which an organism can react to the environment in a more controlled manner. So it is precisely interaction with environment that determines a species’ ability to set mutation, and thus, protein evolution rate.

The authors, however, have a completely different angle in mind. Instead of recognizing that an environmental interplay established this physiological process, we get the following:

“Generally, there are two schools of thought about what affects evolution,” said Andrew P. Allen, Ph.D., a researcher with the National Center for Ecological Analysis and Synthesis in Santa Barbara, Calif. “One says the environment dictates changes that occur in the genome and phenotype of a species, and the other says the DNA mutation rate drives these changes.”

He argues that mutation rate drives the changes through metabolism into the genome. But we just discussed that a species’ metabolism is the byproduct of its interaction with the environment. So why does this dichotomy between “random” mutation and environment persist? My guess is that most research in molecular evolution has focused on variation in DNA, and the framework of thinking about evolution is completely geared towards treating each sample as existing on its own, generated as the product of a chance process. Another approach is to think about mutation as a perturbation of an organism–mutations are inherently part of an organism’s environment. It follows that there are many factors that can then influence the ability of that mutation from altering the genome. This works along the same lines as any other trait that has over time become robust against some environmental/developmental/genetic perturbation.

Finally, this comment really sends off the wrong message:

“We know evolution depends on the environment in which an animal lives,” Gillooly said. “And yet this study suggests that you can look at different species — and without knowing anything at all about their pressures to survive and reproduce in their respective environments — you can draw conclusions about their rates of protein evolution over millions of years. It’s pretty exciting.”

If I interpret this correctly, Gillooly is saying, “Look, evolution depends on environment, but we have this cool correlation between metabolic rate and protein evolution, so really we don’t need the environment to tell us about protein evolution.” This statement is incredibly short-sighed, as it doesn’t bring any theory to try to explain how metabolic rate itself changes. But really it is the environment that affects metabolism. So the fact is exciting, but it doesn’t really help without a bit of theory.

To summarize, I interpret this to say that the authors present evidence suggesting neutral (read: random, unforeseen and uncontrollable mutational events) theory has a more important role is the evolution of life than previously thought. My criticism is that if mutation rate is “strongly influenced” by metabolic rate, and metabolic rate is strongly dependent on a species’ interaction with the environment, then where is the randomness? Not that I think neutrality doesn’t exist, rather I think that we work in a paradigm that pinholes us into thinking about how a piece of DNA changes over time, without consideration to the systemic properties of the organism harboring that DNA, and the environment it lives in which actually presents the mutational perturbations.