Well it takes something like 8 ATP per base pair to replicate DNA, so that’s a pretty hefty metabolic load. Which means, on average, it needs to compensate for that selection pressure somehow. The viruses in our lab will splice out a gene that doesn’t give benefit in maybe around 5 generations? Humans are much better at accurate replication, but I’d still think it would lose it fairly quickly.
ATP may release roughly 14 kcal/mol; the actual amount varies with local conditions (heat, temperature, pressure) and chemical concentrations. An adult human body contains very roughly 50 trillion cells. However, different cells divide at very different rates. I tried to find data estimating total divisions in the body; this Wikipedia article says 10,000 trillion divisions per human lifetime. (Let one lifetime = 80 years ~~ 2.52e9 seconds).
Now, what is a trillion? I shall assume the short scale, trillion = 1e12, and weep at the state of popular scientific literature that counts in “thousands of trillions” instead of actual numbers. This means 10000e12=1e16 cell divisions per lifetime.
We then get 14e3 / 6.022e23 (Avogadro’s constant) = 2.325e-20 calories per extra base pair replication; and 1e16 / 2.52e9 = 3.968e6 cell divisions per second on average. So an extra base pair in all of your cells costs 9.23e-14 calories per day. Note those are actual calories, not the kilocalories sometimes called “calories” marked on food. Over your lifetime an extra base pair would cost 2.325e-4 calories. That’s 0.00000235 kilocalories in your lifetime. You probably can’t make a voluntary muscle movement so small that it wouldn’t burn orders of magnitude more energy.
I am by no means an expert, but I expect evolution can’t act on something that small—it would swamped by environmental differences. A purely nonfunctional extra-base-pair mutation seems to have have an evolutionary cost of pretty much zero if you only count DNA replication costs.
Well, maybe the numbers I got are wrong. Let’s calculate the cost of replicating the whole genome. That’s about 3.2 Gb (giga base pairs), so replicating this would cost 3.2e12*2.325e-20 = 7.44e-8 calories, or 0.2952 calorie/second, or 25.5 kilocalories per day. That sounds reasonable.
What do you think? 8 ATP / base pair replication seems like a tiny energy expenditure. But, I don’t know what the typical scale is for cell biology.
Well first off, I’m going entirely on memory with the 8 ATP number. I’m 90% certain it is at least that much, but 16 is also sticking in my head as a number. The best reference I can give you is probably that you get ~30 ATP per glucose molecule that you digest. (Edit: that’s for aerobic metabolism, not anaerobic. Anaerobic is more like 2 ATP per glucose molecule.)
The other thing to consider is that typically, your cell divisions are going to be concentrated in the first 1/6th of your life or so. So averaging it over 80 years may be a little disingenuous. Cells certainly still grow later in life, but they slow down a lot.
I agree splicing out a single base is not likely to generate any measurable fitness advantage. But if you have 90% of your genome that is “junk”, that’s 0.9*25.5 kcal/day, which is about 1% of a modern daily diet, and probably a much larger portion of the diet in the ancestral environment. Requiring eating 1% more food over the course of one’s lifetime seems to me like it would be significant, or at least approaching it. But what do I know, I’m just guessing, really.
Using 16 ATP instead of 8, and 80/6=13.33 years, won’t change the result significantly. It seems off by many orders of magnitude (to claim natural selection based on energy expenditure).
1% of diet is a selectable-sized difference, certainly. But the selection pressure applies to individual base pair mutations, which are conserved or lost independently of one another (ignoring locality effects etc). The total genome size, or total “junk” size, can’t generate selection pressure unless different humans have significantly different genome size. But it looks like that’s not the case.
But the selection pressure applies to individual base pair mutations
I am confused why you believe this. Evolution need not splice out bases one base at a time. You can easily have replication errors that could splice out tens of thousands of bases at a time.
No, replication is more robust than that. I have never heard of large insertion or deletion in replication, except in highly repetitive regions (and there only dozens of bases, I think).
However, meiotic crossover is sloppy, providing the necessary variation.
Speaking of meiotic crossover, non-coding DNA provides space between coding regions, reducing the likelihood of crossover breaking them.
...I seem to have assumed the number of BP changed by small or point mutations would make up the majority of all BP changed by mutations. (I was probably primed because you started out by talking about the energy cost per BP.) Now that you’ve pointed that out, I have no good reason for that belief. I should look for quantified sources of information.
OK, so now we need to know 1) what metabolic energy order of magnitude is big enough for selection to work, and 2) the distribution of mutation sizes. I don’t feel like looking for this info right now, maybe later. It does seem plausible that for the right values of these two variables, the metabolic costs would be big enough for selection to act against random nonfunctional mutations.
But apparently there is a large amount of nonfunctional DNA, and also I’ve read that some nonfunctional mutations are fixated by drift (i.e. selection is zero on net). That’s some evidence for my guess that some (many?) nonfunctional mutations, maybe only small ones, are too small for selection pressure due to metabolic costs to have much effect.
Yeah, I will definitely concede small ones have negligible costs. And I’m not sure the answer to 1) is known, and I doubt 2) is well quantified. A good rule of thumb for 2) though is that “if you’re asking whether or not it’s possible, it probably is”. At least that’s the rule of thumb I’ve developed from asking questions in classes.
Cool calculation, but just off the top of my head, you would also need energy for DNA repair processes, which my naive guess would be O(n) in DNA length and is constantly ongoing.
Good point. And there may well be other ways that “junk” genes are metabolically expensive. For instance real genes probably aren’t perfectly nonfunctional. Maybe they make the transcription or expression of other genes more (or less) costly, or they use up energy and materials being occasionally transcribed into nonfunctional bits of RNA or protein, or bind some factors, or who knows what else. And then selection can act on that.
But the scale just seems too small for any of that matter in most cases—because it has to matter at the scale of a single base pair, because that’s the size of a mutation and point mutations can be conserved or lost independently of one another.
What is the metabolic cost (per cell per second) scale or order of magnitude where natural selection begins to operate?
Well it takes something like 8 ATP per base pair to replicate DNA, so that’s a pretty hefty metabolic load. Which means, on average, it needs to compensate for that selection pressure somehow. The viruses in our lab will splice out a gene that doesn’t give benefit in maybe around 5 generations? Humans are much better at accurate replication, but I’d still think it would lose it fairly quickly.
I read that and thought: how much is that?
ATP may release roughly 14 kcal/mol; the actual amount varies with local conditions (heat, temperature, pressure) and chemical concentrations. An adult human body contains very roughly 50 trillion cells. However, different cells divide at very different rates. I tried to find data estimating total divisions in the body; this Wikipedia article says 10,000 trillion divisions per human lifetime. (Let one lifetime = 80 years ~~ 2.52e9 seconds).
Now, what is a trillion? I shall assume the short scale, trillion = 1e12, and weep at the state of popular scientific literature that counts in “thousands of trillions” instead of actual numbers. This means 10000e12=1e16 cell divisions per lifetime.
We then get 14e3 / 6.022e23 (Avogadro’s constant) = 2.325e-20 calories per extra base pair replication; and 1e16 / 2.52e9 = 3.968e6 cell divisions per second on average. So an extra base pair in all of your cells costs 9.23e-14 calories per day. Note those are actual calories, not the kilocalories sometimes called “calories” marked on food. Over your lifetime an extra base pair would cost 2.325e-4 calories. That’s 0.00000235 kilocalories in your lifetime. You probably can’t make a voluntary muscle movement so small that it wouldn’t burn orders of magnitude more energy.
I am by no means an expert, but I expect evolution can’t act on something that small—it would swamped by environmental differences. A purely nonfunctional extra-base-pair mutation seems to have have an evolutionary cost of pretty much zero if you only count DNA replication costs.
Well, maybe the numbers I got are wrong. Let’s calculate the cost of replicating the whole genome. That’s about 3.2 Gb (giga base pairs), so replicating this would cost 3.2e12*2.325e-20 = 7.44e-8 calories, or 0.2952 calorie/second, or 25.5 kilocalories per day. That sounds reasonable.
What do you think? 8 ATP / base pair replication seems like a tiny energy expenditure. But, I don’t know what the typical scale is for cell biology.
Well first off, I’m going entirely on memory with the 8 ATP number. I’m 90% certain it is at least that much, but 16 is also sticking in my head as a number. The best reference I can give you is probably that you get ~30 ATP per glucose molecule that you digest. (Edit: that’s for aerobic metabolism, not anaerobic. Anaerobic is more like 2 ATP per glucose molecule.)
The other thing to consider is that typically, your cell divisions are going to be concentrated in the first 1/6th of your life or so. So averaging it over 80 years may be a little disingenuous. Cells certainly still grow later in life, but they slow down a lot.
I agree splicing out a single base is not likely to generate any measurable fitness advantage. But if you have 90% of your genome that is “junk”, that’s 0.9*25.5 kcal/day, which is about 1% of a modern daily diet, and probably a much larger portion of the diet in the ancestral environment. Requiring eating 1% more food over the course of one’s lifetime seems to me like it would be significant, or at least approaching it. But what do I know, I’m just guessing, really.
Thanks for the math though, that was interesting.
Using 16 ATP instead of 8, and 80/6=13.33 years, won’t change the result significantly. It seems off by many orders of magnitude (to claim natural selection based on energy expenditure).
1% of diet is a selectable-sized difference, certainly. But the selection pressure applies to individual base pair mutations, which are conserved or lost independently of one another (ignoring locality effects etc). The total genome size, or total “junk” size, can’t generate selection pressure unless different humans have significantly different genome size. But it looks like that’s not the case.
I am confused why you believe this. Evolution need not splice out bases one base at a time. You can easily have replication errors that could splice out tens of thousands of bases at a time.
No, replication is more robust than that. I have never heard of large insertion or deletion in replication, except in highly repetitive regions (and there only dozens of bases, I think).
However, meiotic crossover is sloppy, providing the necessary variation.
Speaking of meiotic crossover, non-coding DNA provides space between coding regions, reducing the likelihood of crossover breaking them.
Meiotic crossover is what I meant, actually. Generally the polymerase itself wouldn’t skip unless the region is highly repetitive, you’re right.
...I seem to have assumed the number of BP changed by small or point mutations would make up the majority of all BP changed by mutations. (I was probably primed because you started out by talking about the energy cost per BP.) Now that you’ve pointed that out, I have no good reason for that belief. I should look for quantified sources of information.
OK, so now we need to know 1) what metabolic energy order of magnitude is big enough for selection to work, and 2) the distribution of mutation sizes. I don’t feel like looking for this info right now, maybe later. It does seem plausible that for the right values of these two variables, the metabolic costs would be big enough for selection to act against random nonfunctional mutations.
But apparently there is a large amount of nonfunctional DNA, and also I’ve read that some nonfunctional mutations are fixated by drift (i.e. selection is zero on net). That’s some evidence for my guess that some (many?) nonfunctional mutations, maybe only small ones, are too small for selection pressure due to metabolic costs to have much effect.
Yeah, I will definitely concede small ones have negligible costs. And I’m not sure the answer to 1) is known, and I doubt 2) is well quantified. A good rule of thumb for 2) though is that “if you’re asking whether or not it’s possible, it probably is”. At least that’s the rule of thumb I’ve developed from asking questions in classes.
Cool calculation, but just off the top of my head, you would also need energy for DNA repair processes, which my naive guess would be O(n) in DNA length and is constantly ongoing.
Good point. And there may well be other ways that “junk” genes are metabolically expensive. For instance real genes probably aren’t perfectly nonfunctional. Maybe they make the transcription or expression of other genes more (or less) costly, or they use up energy and materials being occasionally transcribed into nonfunctional bits of RNA or protein, or bind some factors, or who knows what else. And then selection can act on that.
But the scale just seems too small for any of that matter in most cases—because it has to matter at the scale of a single base pair, because that’s the size of a mutation and point mutations can be conserved or lost independently of one another.
What is the metabolic cost (per cell per second) scale or order of magnitude where natural selection begins to operate?