That works.
As an aside, @pnelson, will anyone from the orfan group be at the Plant and Animal Genome Meeting? I’m guessing there may be some new gene stuff at this meeting.
1 Like
I’m not going, but I’ll check with the people whose names I can mention publicly, and get back to you.
Seriously @pnelson?
A implies B does not mean not A implies not B. Selection implies function, but neutrality does not imply no function.
How did you misread that?
1 Like
Exactly. This is not a detection of function, per se, but a detection of a statistical pattern in the distribution of substitutions, from which selection is inferred. Function is inferred from selection, not the other way around as you claimed.
2 Likes
But a ruling from @Joe_Felsenstein would be great. Would @pnelson abide by it?
Yes! Having Joe deliver a judgment is like getting the Pope…well, forget that parallel. Maybe something about Sandy Koufax calling balls and strikes at a Little League game.
Must run, because the Peaceful Science kibitzing habit is a black hole for time.
1 Like
Not at your service for Rulings. Busy today and have not had time to read over the pnelson posts.
1 Like
No it does not equal it in the sense that lack of conservation proves to an absolute certainty that there is no function. But it is nevertheless a very good indication.
Speaking colloquially you could say that, if you’re going to try to estimate the functional and the nonfunctional fractions of the genome, you can start by looking at conservation and that will give you a very good outline.
Things are complicated, and in science there is such a thing as nuance and exceptions. But this is an argument about what the true proportions are, you don’t establish that by waving your hands vaguely in the direction of examples where a functional non-coding sequence was found. Particularly when this was never truly about coding vs noncoding, but about functional vs nonfunctional.
If you’re going to make any sort of argument against using conservation to get a good handle on the fraction of the genome that is functional, you’re going to need to show that unconserved regions of the genome are consistently full of important functions(not to be confused with merely being implicated in disease).
If you’d like to provide an opinion and avoid searching for the at-issue post, see the details pasted below:
That test attempts to detect positive selection by finding changes that exceed the number expected from neutral evolution. “Adaptive evolution” is inferred from the rate of change, not from any analysis of function, as Nelson seems to imply.
2 Likes
I’ve tried to be diplomatic in the about this, but bluntly speaking the definition of fitness is total disaster and renders notions of “beneficial”, “neutral”, “deleterious” relatively moot!
John Sanford’s Genetic Entropy 1.0 used the pop gen definition of absolute Darwinian fitness which is basically the number of offspring each individual had, or the number offspring related to an allele, or some characteristic of an organism.
I’ve suggested Genetic Entropy 2.0 avoid the mess of pop gen definitions altogether.
In a 2009 paper on fitness, Allen Orr quipped, “biologists have offered a staggering number of definitions of fitness”, and in 2003 Lewontin lamented, “it is not entirely clear what fitness is”.
Lewontin made a biting criticism:
The problem is that it is not entirely clear what fitness is. Darwin took the
metaphorical sense of fitness literally. The natural properties of different types resulted in their differential “fit” into the environment in which they lived.
The better the fit to the environment the more likely they were to survive and the greater their rate of reproduction. This differential rate of reproduction
would then result in a change of abundance of the different
types.
In modern evolutionary theory, however, “fitness” is no longer a characterization of the relation of the organism to the environment that leads to reproductive
consequences, but is meant to be a quantitative expression of the differential reproductive schedules themselves. Darwin’s sense of fit has been completely
bypassed.
–Lewontin, Santa Fe Winter Bulletin 2003
I’m sad to have to say that I think your characterization here is rather misleading, Paul. In reality it is the other way around.
Neutrality(due to lack of function) is a null hypothesis that can be rejected by experimental findings. Having a null hypothesis that can be easily rejected in practice by a simple experimental observation is actually a basis for good reasearch.
See for example:
Koonin EV. Splendor and misery of adaptation, or the importance of neutral null for understanding evolution. BMC Biol. 2016 Dec 23;14(1):114. DOI:
10.1186/s12915-016-0338-2
And here is a good blog post on a similarly relevant topic:
If you’re going to start by saying everything is functional until proven otherwise, you just don’t know how right now, then you can always keep stipulating that you just haven’t found out how it is functional even where experiments reveal no apparent effects from changing or deleting the locus. Perhaps, you might say, we just haven’t found the right and special circumstance under which this particular locus contributes to organismal function. And then you could waste a century and incredible amounts of money studying that one locus under any and all imaginable circumstance in search of that one special function you still haven’t disproven might exist.
However, if you stipulate instead, at least based to a first approximation on conservation, that the locus is nonfunctional if it evolves at a neutral rate, then it becomes rather simple to reject the null hypothesis. See what effects changes to the locus has, and infer it’s putative function from that, and you have then rejected the null.
Now, if you also were to use conservation as a guide to what locus you should study first, you’re more likely to find important organismal functions if they’ve been conserved across your phylogeny, for reasons that should be fairly obvious. That way you would quickly find yourself to be studying essential genes in core metabolism and development. As you chew through the conserved regions of the genome first, you are more likely to find the most important functions first, and then eventually you can move on to less conserved regions.
You could use it as a guide towards relative priority here. There is limited time and resources, and the genome is big and complicated, and figuring out how things work take a lot of time and money. So it actually helps to have a guide to prioritize some more promising regions over other less promising ones. That is not to say you shouldn’t ever look at less promising regions, just be smart about it.
Further still, these points are relatively moot here, because most of the ways the genome is studied today, at least in terms of medicine, is through Genome-Wide Association Studies. People with certain symptoms go to their doctor, and some of them get referred to specialists and university hospitals studying the fundamentals of what is causing those symptoms of disease. There eventually some loci are discovered to be associated with those symptoms. This then provides the basis for more closely examining how those loci work, what it is that happens at the genetic and cellular level to cause the symptoms in those patients.
At no point, ever, do evolutionary biologist come crashing through the door insisting that they stop studying the implicated locus because it’s been poorly conserved. This simply doesn’t happen anywhere. It’s not how this research is conducted at all. You are creating a misleading fantasy of how genetic research occurs.
2 Likes
Nobody expects the evolutionary inquisition! Our chief method is data and analysis. Our two chief methods…I’ll come in again.
2 Likes
I never made that argument.
What you need to explain is how a DNA sequence can have its function uninterrupted while mutations are occurring within that sequence at a rate consistent with neutral drift.
3 Likes
There is the possibility that the locus has very recently evolved to become functional in a particular species, but up until that point has been evolving neutrally. That probably does happen, but such cases are bound to be comparatively rare, and it would be better to prioritize your time to first studying conserved regions, and then move on from there once you’ve got a handle on that.
This is all supposing genetics research is conducted in the strange way Paul Nelson insinuates, where biologists are pretty much blindly picking genetic loci to figure out how works. Of course, that isn’t how it is actually done in practice.
1 Like
I think that instead of “mutations” you mean “substitutions”. In neutral drift, of course, the two are equal. But not otherwise. If we see substitutions at less than the mutation (or neutral evolution) rate, we infer conservation, purifying selection. If we see substitutions at greater than the mutation rate, we infer positive, adaptive selection. Conceivably the latter is what Paul was trying to imply, though that isn’t clear.
1 Like
“It deosn’t mttaer in waht oredr the ltteers in a wrod are, the olny iprmoetnt tihng is taht the frist and lsat ltteer be at the rghit pclae. The rset can be a toatl mses and you can sitll raed it wouthit porbelm. Tihs is bcuseae the huamn mnid deos not raed ervey lteter by istlef, but the wrod as a wlohe.”
If essential function is preserved, neutral changes can (and will) accumulate.
And do you think that a single one of them would say, “Golly gee, Josh, I see your point. Our past rhetoric on this makes no sense at all,” after you showed them?
1 Like
In the case of humans, this would imply that nearly 80% of the human genome has acquired new function in very recent times. I don’t see the ID crowd supporting such an idea.
1 Like
How does this work in DNA?
We are told time and time again how rare function is in sequence space, but now you are telling us that no matter how much you change a DNA sequence it will keep its function. That doesn’t make sense.
4 Likes