I have a subscription to the science journal Science, but I rarely do more than shuffle through the contents every 6-8 issues. While it’s considered one of the premier science journals, there are a lot of articles that are not applicable to what I do, so I usually choose to focus my attention on journals more closely aligned with my research. However, I happened to look at the October 14, 2011 issue of Science and I’m happy I did! I came across a great paper by Nick Lane that proposes a possible link between respiration and fitness, fertility, and life span within eukaryotes and explains how this might work. I’ll talk about Lane’s hypothesis today, but I want to go a step further too. The examples in the article are all vertebrates and the hypothesis fits well to these organisms. But how well does it fit with insects? I’ll discuss that at the end.
Note: if you don’t remember what the respiratory chain of cellular respiration is, you’re likely to get a little lost as you read through this. I created a handy-dandy respiration refresher yesterday though, so you might want to take a look at that before you go any further.
Lane begins his paper by describing how respiration depends on two different sets of genes within cells, the mitochondrial genome (the genes found in the mitochondria) and the nuclear genome (the genes found in the cell nucleus). The mitochondrial genome is passed directly from a mother to her offspring while the nuclear genome results from the combination of genes contributed by the mother and the father. These two genomes must work together to create a functional respiratory chain, the important last step in cellular respiration. If the mitochondrial and nuclear genomes are perfectly compatible, the respiratory chain will work nearly flawlessly and produce ATP and water as it should. If there is a mismatch between genomes such that the respiratory chain develops incorrectly, electrons can escape the respiratory chain and react with oxygen to form free radicals, specifically reactive oxygen species (ROS). Leaks in the respiratory chain can result in excessive ROS production, which can in turn cause damage and even programmed cell death. It is thus essential that the mitonuclear compatibility be sufficient to form a functional respiratory chain capable of supporting an organism’s energy requirements. In fact, offspring with severe mitonuclear mismatches will likely die during development or shortly after birth, leaving only those individuals with functional cellular respiration alive to reproduce.
But, Lane wondered, how good does this mitonuclear match really need to be for an organism to survive? Consider an animal with a high metabolic rate such as a hummingbird or a bat. These animals must have high mitonuclear compatibility to produce a respiratory chain capable of supporting the high energy demands of flight. In these animals, any individual with even a minor mitochondrial mismatch should die because it cannot produce the necessary energy to survive. However, more sedentary animals, such as rats and other rodents, can likely tolerate a higher ROS leak because their energy demands are lower. It’s not as crucial that every electron make it to the end of the respiratory chain in these species. If so, then offspring with mitonuclear mismatch (up to a point, the ROS threshold) may survive long enough to pass their genes on.
Let’s consider what this hypothesis, if correct, means with regard to reproductive success (i.e. fitness), fertility, and life span. Think about the hummingbird and the rat for a moment. If the hummingbird requires low ROS leakage, many of its offspring are likely to die during development because the ROS leakage threshold is low. In contrast, a rat has a higher ROS leakage threshold and more of its offspring will survive relative to the hummingbird. This means that fertility should be low in hummingbirds and high in rats, which is indeed the case. Fitness could also be affected by ROS leakage thresholds. Hummingbirds have fewer offspring relative to rats, but their offspring are also less likely to survive to reproduce themselves if their ROS threshold is very low. But there’s a trade-off too (there’s almost always a trade-off in biology!): a higher ROS leakage threshold means that more ROS are being formed. Excessive free radicals can lead to cellular damage and death. Rats, with their higher ROS leakage threshold, will have a higher ROS production as well as higher cell damage. High free radical production is known to decrease life span, so the rat, with its high ROS production relative to the hummingbird, will have a shorter life than the hummingbird.
So Lane’s hypothesis fits the data for terrestrial vertebrates very well and he has generated a testable idea that people will be able to experimentally support or refute. That’s good! I think this idea, that a cellular process helps determine fitness, fertility, and life span, is very interesting and I’m eager to see the research that results from this paper. However, at the end of the paper Lane suggests that the ROS leak hypothesis should apply across species, presumably across eukaryotic species such as fungi, plants, and invertebrates. He might be right, but let’s consider insects for a moment. There’s nearly always an exception among insects, and I think this is a case where there might be a big exception.
Let’s think about flies for a moment. Many flies have high metabolic rates, which, according to Lane’s hypothesis, should mean that their ROS leak threshold is low with a corresponding low fertility and long life. This isn’t necessarily the case. Some flies produce few offspring, but many of them produce a lot of offspring! Many flies also have very short lifespans of only a few weeks from egg to dead adult. Let’s then contrast this to the flightless giant water bug I work with (not an altogether fair comparison as they are larger than most flies and that needs to be taken into account, but this is just a thought experiment). The water bug spends most of its life sitting in one place, a highly sedentary insect with a low metabolic rate. If Lane’s hypothesis applies to all eukaryotes, this giant water bug should have a short life and high fitness. Giant water bugs have huge eggs, so they don’t produce as many offspring as some species, but 1000 or more offspring in a mating season is nothing to sneeze at and they seem to fit Lane’s hypothesis. However, these bugs tend to have comparatively long life spans, sometimes a year and a half as adults! Last, think about social insect queens. These are sedentary insects that sometimes have very long lifespans (sometimes decades long!). According to Lane’s hypothesis, these insects should have short lifespans, which isn’t always the case.
I don’t want to sound like I think Lane’s hypothesis is worthless because I think it can potentially explain several patterns of metabolism, fitness, and life span that we see in nature and I honestly hope it pans out. However, I have two predictions, one or both of which I suspect will hold true as researchers begin exploring the limits of the hypothesis:
Prediction 1. The ROS hypothesis will not apply to all eukaryotes and instead apply mainly to warm-blooded, terrestrial vertebrates.
Prediction 2. If the hypothesis holds up to experimentation, I suspect researchers will find other forces at play in insects and other invertebrates that overshadow or alter the impact of ROS leaks on life span and fitness so that they do not follow the same patterns that we see in warm-blooded, terrestrial vertebrates.
Ultimately, I don’t think the hypothesis in its current state is going to be as widely applicable to eukaryotes as Lane suggests, but I hope it will lead to some interesting new research dealing with the link between cellular processes and the life histories of organisms. If it does that, even if it proves to be incorrect, I think this hypothesis can contribute something very meaningful to science. And even if it doesn’t pan out, at least it was an exciting idea that got people thinking. I consider that a success!
Lane, N. (2011). The Costs of Breathing Science, 334 (6053), 184-185 DOI: 10.1126/science.1214012
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