Of Mice and Men: How does the biology of running evolve?

Mobility as an Emergent Property of Biological Organization: Insights from Experimental Evolution

Evolutionary Anthropology just published a fantastic article (linked above, full text) summarizing 20 years of research with mice selectively bred to run.  That is, mice that voluntarily run more distance per day have been bred together for generations, producing mice that are biologically better at running, and willingly run longer each day, than other mice.  If you're wondering how this is informative or productive: selective breeding is used by scientists all the time to understand how real evolution occurs and how biology changes as particular traits become more common.  Selective breeding is a lab-controlled simulation of real selection-- natural selection-- that occurs in nature.  In this case, these studies have produced some fascinating insights into how evolution produces a biologically-equipped mammalian runner.  As we are also mammals, these mice studies raise all kinds of testable questions regarding the evolution of human running. 

For anyone not wishing to chew on the review article above (though it is very digestible, I think, perhaps even for non-science folks), here I'll summarize the significant differences that have been observed in running-bred vs. non-running mice. (Note that these closely, but do not entirely, follow the bullet points in the article.)

Mice bred to voluntary run more have led to generations of mice that, well, run more.  (Mostly because they run faster, actually.)

What mice tell us about the evolution of running

1. Running is compelled by biology.  You and I might consciously decide to head out the door for a run because we know it will make us feel good.  Or lose weight. Or whatever.  Other cursorial (running) animals aren't motivated by this foresight but rather by unconscious drives.  These drives (which we have too! Check out "Wired to Run"-- your brain makes pot-like chemicals when you run) directly motivate animals to move.  They have likely evolved because running serves some survival purpose.  In mice, I have no idea what that could be, but in dogs and wolves, it's food acquisition: an animal that is motivated to run covers more territory and finds more food.  Hence, those genes are passed on more successfully than couch-potato dogs, and so evolution goes.  We know that the drive to run in the running-bred mice is genetic and biological, and not learned, because it is present early in a running-bred mouse's little life, before they have had a chance to get used to a running wheel.  In short: the urge to run can be genetic and biological, and therefore it can evolve through natural selection.

What are some of the mechanisms of this biology that motivates animals to run?  Well, in humans and dogs, it's the aforementioned endocannabinoids (see link above).  In mice it seems to be a change in how the brain chemical dopamine functions.  Here's an example of "convergent evolution"-- similar solutions arising independently in different animal species to solve the same problem. 

2. Selection for increased motivation to run, and running ability, comes with lots of biological changes.  Some are mentioned above-- changes in reward pathways in the brain which encourage animals to run.  In wolves and dogs--who clearly have an excellent evolved running capability- certain biological traits have an obvious positive effect on running performance: muscle composition, leg length, etc.  But the selective breeding experiments with mice demonstrate how some of these characteristics can evolve, or change, from a baseline population of non-running-adapted animals.  Running mice, over generations, developed a higher VO2-max (oxygen carrying capacity) than non running mice; decreased body size, leading to more efficient running; decreased calf muscle size, which is good for endurance running because it reduces the weight lifted with each stride; increased midbrain size (possibly to increase the reward pathways discussed earlier, or to aid in coordination); increased surface area in the leg joints, good for shock absorption; and intriguingly, differently-shaped semicircular canals, which are structures in the head important for balance and thought to be essential for frequent and effective endurance running.  I say "intriguing" because this last observation is also seen in the fossil record early in our genus, as are many of the other evolved traits of the running-bred mice.  It would be rash to directly apply observations of artificial selection in mice to human evolution, but these results (to me) point to things we should look for in human evolutionary history when testing hypotheses about whether, when and how humans evolved to run.  And the fact that we see similar traits in humans is tantalizing. The takeaway: selection for increased running performance does indeed lead to genetic, biological changes that improve running ability.

3. Evolved running ability comes at a cost, and is constrained by evolutionary "trade offs".

I often joke that the better I get at running, the worse I get at everything else.  There is truth in this at an evolutionary level: traits that enhance one thing will likely have a negative (or sometimes positive) impact on other things.  A great example is Herman Ponzter's observation that, in cursorial mammals, hind limb length has evolved for running efficiency, but only to a point: super long limbs would cost a lot to grow during development and would decrease sprinting speed far too much.  When evolutionary costs outweigh benefits, a trait will cease to become more pronounced over time- it will have reached an equilibrium of sorts, a compromise.  Similar constraints are observed in the "evolution" of our running mice.  Their reduced calf musculature makes them slower sprinters, and in a natural setting with predators, natural selection would likely work to reduce this calf-shrinking trend, despite any advantages it might convey for endurance running, which for mice would be almost nothing-- they are not endurance runners, let's remember.  (Interestingly, as an aside, this trait is caused by a single allele for a single gene. Also interesting is that the size and location of calf musculature in human runners has a significant effect on running economy.) This trade-off between endurance and speed surely limits the endurance-running adaptations that any cursorial animal develops.  Perhaps humans too, though sprinting can't have been especially helpful to us in my opinion, because even Usain Bolt would have trouble outsprinting an African carnivore.  

Anther tradeoff observed in mice: increased corticosterone levels in the running-adapted mice is helpful in that it increases fuel availability for muscles and encourages running behavior, but decreases immune function, inhibits growth, and may lead to depression (sad little mice). The first two effects, if at play in the evolution of any running species in a real setting, would incur significant fitness penalties and would therefore be highly constrained. 

Finally, like any other complex trait, endurance running motivation and ability is influenced by many genes, some of which have many different jobs and effects.  (This is called "pleiotropy".) This helps explain the trade-offs mentioned above, but it also explains some of the stranger results found in the mice study, like the observation that running mice "build smaller nests in their home cages, display greater predatory aggression towards crickets, and have a slightly altered finger-digit ratio".  The latter is also found in humans to predict athletic and running ability.  Like the other weird observations, finger ratios have no direct effect on running performance, in humans or mice.  Rather, they are influenced by similar genes, like the ones encoding the hormone testosterone.  Genetic changes that evolve to enhance running ability also have other weird side effects that will simply come along for the ride, and won't be selected against unless they are super deleterious.

Unfortunately (or maybe fortunately for me) there are still very few researchers asking evolutionary questions about human running, so it will be years before some of these insights are applied to humans.