Sorry for the copy-pasting myself here, but I’m reminded again of what Thornton and colleagues write here:
Distantly related genes (or regulatory elements) typically differ at many sequence sites – not only those that caused functional change but also those that diversified during subsequent periods of functional conservation and sequence drift – complicating efforts to identify the effect of specific substitutions (Rebeiz et al., 2015; Hochberg and Thornton, 2017). Epistasis among sites within loci represents a further challenge, because mutations introduced into present-day sequences often have effects different from those they had during historical evolution (Bridgham et al., 2009; Natarajan et al., 2013; Ortlund et al., 2007). In such cases, sequence differences that were causal in the past can be masked in horizontal swap experiments, leading to false negative inferences concerning the mutation’s effects; alternatively, if a sequence state from one lineage is swapped into a present-day gene with which it is epistatically incompatible, that state may appear to have been the evolutionary cause of a null phenotype, a particular problem if the diversity being studied involves the absence of a structure or function (Hochberg and Thornton, 2017). Epistasis between loci presents another difficulty: when a putatively causal factor, such as a regulatory protein or DNA element, is swapped horizontally from one species into a model organism to test its causal role and recapitulates the phenotype from the ‘source’ species, this provides strong evidence for causality, but a negative result could arise because of an epistatic ‘mismatch’ between the swapped factor and other loci. The more distantly diverged the two species, the more significant this problem becomes (Gehrke and Shubin, 2016 ).
This communicates a concept I’ve tried to get across many times, which is that things used to be different back when whatever system you’re thinking of first evolved. Whether that is some particular protein in a bacterial flagellum, an organ or tissue in a multicellular organism, or some other limb/morphological structure. It just doesn’t make sense to speak about it’s presence or absence today being somehow essential or detrimental to an extant organism, as it has to be considered in the context of what the organism and it’s environment was like at that duration of time when it first evolved.
And transferring a gene with a particular mutation that uniquely evolved in the human lineage, into an entirely different organism we share a common ancestor with over 50 million years ago makes the issue all the more pertinent. That just makes it all the more difficult to make conclusive statements about what would or wouldn’t be possible.
This is true of every point mutation in the cosmos.
There are almost certainly people born with that particular point mutation, if there is a point mutation that can reintroduce the stop codon into the Arghap11b coding sequence. I haven’t seen any reports of this. If they existed (the reports) they could provide evidence about the role of the protein in today’s brains.
That question is pretty garbled but the mutation that we’re discussing causes a quantitative change in the numbers of neural progenitors and upper-layer cortical neurons in a primate. That seems very unlikely to be neutral to me, but since you have read my previous posts, you know that we don’t know the precise genomic or physiological context into which the mutation was introduced.
All point mutations are “reversible,” though the term that geneticists use is ‘revert’ and ‘reversion’. In an evolutionary context, it is not usually reversion, but fixation, that matters, since once a mutation or any polymorphism exists in a population, then its frequency becomes the most relevant evolutionary measurement.
Yes, that’s true of every nucleotide change in every genome on the planet, past and present. Since this one was fixed in the population, your questions are likely not germane at all. I hope you understand why.
Not as far as I know. Too simplistic. In relatively small populations, like the one we would assume we are talking about here, the biggest risks to a new mutation are negative selection and drift. Reversion is not a quantitatively relevant factor.
I don’t know who’s talking about that. “Several generations”???
There’s no such thing as an irreversible mutation, and there’s no good reason to think that “this mutation” exerted strong negative selection. More importantly, this mutation is already fixed in our lineage, so these questions are frankly bizarre.
I encourage you to read the thread and perhaps the abstract of the paper. It’s not about selection or population genetics. It’s actually easy to discern what the paper is about, and it’s not about evolution.
Yes, there is always such a probability. All mutations are in principle reversible. For every possible mutation there is the complementary reversal. G can be substituted for A, and A for G. Any duplication can in principle be deleted again, etc. But the probabilities are rarely, if ever, equal.
If so, shouldn’t there be people who are born with this mutation reversed?
That obviously depends on the probability of reversion, so no it doesn’t automatically follow that there should be a person with this exact mutation reversed. It might even be the case that the mutation now epistatically interacts with other genetic loci such that reversion is highly deleterious, and hence our species could have evolved subsequently to the first emergence of this mutation such that any putative developing embryo with a reversal could have become non-viable in the interim.
If you are building a structure that just consists of four posts embedded in the ground in a rectangular pattern, you can then change your mind and remove one of the posts without causing any damage to the remaining structure. But if you proceeed to build an entire hut on top of the posts as shown in the image, then you cannot remove one of the posts without the whole thing collapsing.
They would also be concerned about any pain or suffering the mutation would case. We simply can’t know what this mutation will do in the maromoset genetic background.
Thanks for the reply.
It helped me understand your post better…
You wrote:
“There are almost certainly people born with that particular point mutation, if there is a point mutation that can reintroduce the stop codon into the Arghap11b coding sequence. I haven’t seen any reports of this. If they existed (the reports) they could provide evidence about the role of the protein in today’s brains.”
This is an interesting point. But, isn’t it established that the protein increases cognitive capacity?
One thing is for certain. There is a big difference between your explanation and what the article says. I guess I will have to read the paper.
Nope. That’s nowhere in this thread or in any of the papers published on the protein. I think it’s a very reasonable hypothesis but no one has shown it. That would be a very hard thing to do.
I hope that’s not true, since I read the paper (unlike, I think, anyone else in this conversation) and tried hard to explain its findings. I will be very eager to know about any differences so I can correct them.
