Genetic Equidistance: A Puzzle in Biology?

I've mostly covered this in the other thread, but the quick answer is that we know that genetic distance is the result of time and not a pattern of increasing constraint on organisms, because we measure genetic distance based on genes that are subject to far greater restriction as a result of function than they could possibly be subject to as a result of increasing complexity - cytochrome c, ribosomal subunit 16S, and so on. These proteins have identical functions regardless of cell type, cell diversity, or organism complexity. Every cell in your body, for instance, needs to express proteins.Also, a pattern of increased restraint on tolerance of mutations wouldn't produce genetic equidistance, it would produce a pattern of decreasing distance as a result of complexity. Under your model, humans would exhibit less genetic distance from yeasts than trout do, but what we observe is that both humans and trout exhibit equidistance from yeasts, reflecting the evolutionary time since the line that resulted in modern humans diverged from the line that resulted in modern trout.Edited by crashfrog, : Whew, run-on!Edited by Adminnemooseus, : Added link to most recent relevant message in "other thread".

I'm not sure you know any biochemistry. This makes no sense. Every single amino acid can be found in every single human cell, so there's no such thing as a substitution that would be "incompatible" with the cell. Now it is indeed possible for the function of a protein to be eliminated by even a single substitution - say, a substitution that disrupts a critical hydrophobic region and alters protein folding and disrupting an active site, or eliminates or moves a critical catalytic residue. But that's going to have nothing to do with cell diversity. No, this makes no sense. Protein A may not be expressed in X, Y, or Z, or it may be subject to alternate splicing such that the mutation in the gene for A is in a region that is not expressed in one of those cells. And really, there's no such thing as "cell type", there's just different patterns of gene expression and regulation in different cells. The fact that two different cells may have different patterns of gene expression really doesn't say anything at all about which mutations will prove fatal in which cells. No, it remains pertinent. Regardless of cell type, all cells in your body are engaged in electron transport chain activity - you breathe air, I assume? - and protein translation. What is your source for this observation? And I don't see the relevance - your model doesn't explain it either, and it's a perfectly explainable observation under the scientific consensus of evolution. I never said that it was not. The functional residues of cytochrome C are very highly conserved; almost no organism can tolerate any mutation of these residues. We're talking about residues that are not related to catalytic function.We're talking about silent mutations, in other words, and since these mutations are silent cell type and tolerance is irrelevant - a cell can tolerate any number of silent mutations because they don't change protein function.

I never said that they were. But, clearly, proteins subject to less conservation are subject to more selection, and selection alters genes in different ways that genetic drift. So, selection-heavy proteins are less likely to exhibit genetic equidistance. This pattern is observed. I know, and this is utterly wrong. Cytochrome c isn't in the environment of the cell, it's buried deep in the intermembranous space of the mitochondria, and from that perspective all cells are basically the same. There's nothing in the pattern of protein expression and regulation - which is what actually makes cells different from each other - that's going to "check" mutations to cytochrome c. The only thing that's going to "check" a mutation in cytC is whether or not it still has electron transport activity. Oxidative phosphorylation is essentially the same in all eukaryotic cells which is why it's such a canonical metabolic pathway. No, it's not. If Shi Huang says this, Shi is wrong. But I suspect you've simply got your wires crossed.

Genetic distance is measured primarily on non-coding regions to minimize the effect of selection, so, by definition, your model of equidistance being the result of increased selection against mutations in more complex organisms is false.

You're right, of course. My bad.

I promise not to hold it against you that you are young, or early in your academic career. I am not particularly further along myself. And I would never hold it against someone for being open and honest about how their views have changed, since mine change all the time.The only thing I will try to pin you on is where you make authoritative claims of fact that are wrong. I hope you (and others, like Taz) will do the same to me when I do it.Thanks for sharing. Now I'll share - I think the most fruitful line of attack is the way in which you characterize a deleterious substitution mutation as an "incompatibility with cell type." I think this is a unclarifying way to look at mutations. A deleterious amino acid substitution in cytochrome c, for instance, is going to be lethal to the cell regardless of cell type because electron chain activity is critical for meeting the cell's energy budget. Most deleterious mutations are deleterious because the structural change to the protein eliminates its function, and that function is crucial to the life of the cell. Some number of mutations are going to be deleterious because they change the way the protein interacts with other components of the cell, or they may introduce a new interaction with the cell, but actual cell type isn't going to have much to do with that. Interaction-based deleteriousness happens at a finer grain of cellular environment than "this is a liver cell; this is a muscle cell."There's just nothing in biochemistry that would allow you to confidently make the prediction you're making, to wit: that an increase in cell diversity in a given species is going to result in more mutations being deleterious instead of neutral. The vast majority of proteins in a cell have the same function regardless of what kind of cell they're in.

I don't think a priori you can make such a statement, since there's too many confounding factors. Most proteins in the cell have no idea whether they're in a liver cell, or a brain cell, or a pancreatic cell.Obviously cell environment has an effect on which mutations prove to be deleterious, because some of that effect is the result of changes in a protein's interactions with other components of the cell environment. But to predict the effect of diversity of cell environment on a mutated protein (and vice-versa) you need a finer-grained study than "liver cell; muscle cell." Well, it's a standard practice in constructing phylogenies to use proteins with identical function across the compared clades. That would seem to rule out any effect of diversity of cell environment. Cytochrome c is going to be highly conserved regardless of what kind of cell we're talking about.

What direct effect does cytochrome c have on biological activity outside the mitochondria? No, I don't suggest that. I suggested the exact opposite - that there were many mutations whose degree of deleteriousness depends entirely on the interactions of the protein with other cellular components. In fact you quoted me saying precisely that. So why pretend that I'm saying something that I'm not?And you were starting out so well. This is a great deal of observation marshaled against a position I don't hold. You'd do a lot better trying to find evidence for your own position.

In many cases, the cell can only function because things are not connected. A cell with no ability to sequester some molecules from others is a cell that rapidly enters chemical equilibrium with its environment - i.e., dies. Well, ok, but a minute ago you seemed to be reasoning from the assumption that there was. This is certainly something that happens. There's not any reason to think that it happens in enough cases to substantially throw off our confidence in molecular phylogenies.

Yes, there are. The cell is such a complex place that you really can't say, except in the specific, whether or not mutations are related to cell type diversity. I don't believe that you can make that characterization. There are definitely proteins for which that is apparently true, like tRNA-glycine amino-acyl transferase in humans. There are proteins for which that doesn't seem to be true, like cytochrome c or ribosomal subunit 16S. The only reason to expect that a putative molecular phylogeny is going to be confounded by cell diversity effects is if the phylogeny is constructed on the basis of proteins that have that kind of relationship with their cellular environment.Are they? When you look at tissue-specific genes. That's not in dispute. What's in dispute is that all genes on which phylogenies are constructed are tissue-specific. They are, in fact, not.