He’s saying that horribly bad things happen in evolution, and no good things.
Natural selection resists synteny changes.
Natural selection also resists changes in gene sequences that cause missense mutations.
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I think it would help to step back and get a clearer picture of just what @stcordova is imagining here.
At the risk of dating myself, I think it is helpful to recall some history. Way back in the day, and indeed even today, people have been characterizing promoters by arranging relative short (100-10,000 bp) regions (typically, “upstream” of the transcription start site of the gene that was the focus of some poor grad student’s thesis, of their entire life) so that they could drive the expression of an easily-assayed reporter (lacZ, beta-glucuronidase, chloramphenical acetyltransferase, luciferase, GFP, to name a few). These DNA constructs (again, a few thousands of bp in length) were introduced into an appropriate cell or organismal system and the expression of the reporter assayed. These DNA constructs usually had two fates inside of cells - they existed as extra-chromosomal elements or they were randomly integrated into the host cell genome.
The great thing about these many thousands of experiments is that, collectively, they worked. They provided us with an accurate and very useful foundation whereby cis elements were defined, transcription factors identified, and countless instances of regulated transcription worked out. Again, I will stress - they worked.
@stcordova, my question for you is this - you seem to be taken with the notion that transcription is a function of some large, hopelessly convoluted, intricately arranged multidimensional construct. How do you reconcile your idea with the thousands upon thousands of successful experiments, most or all of which involved the study of enhancers far removed from their original chromosomal context?
Robustness and redundancy. Brenda Andrews high throughput experiments showed even 1-level knockouts of GENES didn’t compromise fitness in many cases.
Simple disruption experiments aren’t the final word, obviously.
This doesn’t answer my question. I was not referring to knockouts and the like, but rather to the fact that promoters work just fine outside of the context you think panel C in the figure above presents. How do you think this can be, if your idea of the 4D Nucleome is correct?
I thought it did, but even in the above paper I cited from where the diagram came from:
A model for essential and redundant functions of an OR enhancer in cis and in trans, respectively. Schematic representations of different states in the olfactory sensory neuron nucleus (left) and corresponding transcriptional outputs (right) are shown. An OR gene (orange box) located proximal to an enhancer (orange circle) is repressed by H3K9me3 (red flag, A). The cis-proximal enhancer may facilitate derepression of the OR chromatin landscape (green flag, B), but is not sufficient for OR transcription. Multiple trans-interacting enhancers (colored circles) aggregate around the transcribed cis-proximal OR (orange box, C). This model of enhancer–promoter configuration can explain why some enhancers are required in cis but are redundant in trans.
So my answer is redundancy and robustness, just as I said earlier.
I’m afraid you don’t understand the figure or the reasons the authors put it in their review. Have you read it?
Redundancy and robustness does not answer my question. Because part of what I am asking about is promoters that have no chromosomal context - the gene on Chr 14 in the figure is completely removed from the network that might provide robustness and redundancy. How do you explain this?
Just to let you know where this is heading - the answer to my question is also the answer to the challenge you believe synteny poses for evolution.
Alright I’ll look into it more. Thanks for taking the time to write detailed replies.
If they’re deleterious.
If they’re deleterious.
If they’re deleterious.
If.
Natural selection resists deleterious changes, but facilitates beneficial changes, and does nothing in particular about neutral changes.
And?
Natural selection doesn’t “resist” anything. Certain genotypes have higher selection coefficients than certain others. What you’re saying is that mutations that change synteny are very likely to be deleterious. That may be true, though you present no evidence.
What you mean is that missense mutations are likely to be deleterious. That much is clear, since indels in exons are much rarer than in, say, introns, and those that we see are usually in multiples of 3 bases.
This sort of thing is not clear for Sal’s claim. Mutations that change synteny are translocations, and there’s nothing to compare the frequency of translocations to, as there is for indels in exons. You would need data on the frequency of translocation mutations occurring in populations vs. the frequency of their fixation. I doubt he has any.
The evidence is mixed, but first evidence that translocations are bad (and translocations are a necessary but not sufficient path to synteny change):
Other genetic dysfunctions (e.g. inversions and translocations) can also dramatically reduce fertility in higher plants, although these do not appear to be important in redshank. Chromosomal translocations can produce ovule abortion rates of 50–90% in some species (Lewis & Szweykowski, 1964; James, 1978).
https://onlinelibrary.wiley.com/doi/10.1111/j.1095-8312.2011.01820.x
Incidentally I learned of Wien’s work at the Christian Scholars Conference at Lipscomb where I made a presentation on ENCODE.
I’ll provide some evidence of cases where translocations might not be quite so bad in a subsequent comment.
Ok some evidence synteny change isn’t always catastrophic, from Bruce Alberts book, Essential Cell Biology:
As I mentioned even in humans, cardiac myocite cells are polyploid and so are other cells. Incorporating these facts in to the 4D nucleome perspective is something of future investigation.
But in general, I think it’s premature to assert synteny change can evolve naturally and easily. It would seem at least some synteny changes will be resisted by natural selection. The problem, like so many problems in evolutionary theory, is that it is merely assumed such evolution is normative when in may well take miracles to effect.
FYI: regarding cardiomyocyte polyploid cells:
I recommend Dave Wisker’s series at The Panda’s Thumb:
The Rise of Human Chromosome 2: The Dicentric Problem
The Rise of Human Chromosome 2: The Fertility Problem
The Rise of Human Chromosome 2: Beyond the Deme
No, the evidence is misinterpreted. Translocations decrease fertility not because they alter synteny but because they can result in improper chromosome pairing during meiosis.
Better evidence: synteny can vary through the tree of life. You of course would deny that such a tree exists, but that isn’t my problem.
You mean “some” rather than “at least some”. Right? Also, I think “resisted” is a very poor word choice.
Are you moving over to guided evolution from creationism? If not, that sentence makes no sense.
That wasn’t the argument.
How can synteny be altred without translocation being selected for or at least being tolerated?
I don’t think you understand your own argument. You were talking about synteny conservation as evidence for your 100% functional genome. I point out that you don’t need that assumption to have synteny conservation.
No I wasn’t.
I said, NS resists evolution of synteny changes.
I argued for high percentages of functional genome from other considerations like experimental observations.
I could probably take a really small needle-like drill and drill out a small part of the tread of the tire, and the tire functions. I can then take another tire and do the same experiment but on a different location on the tire. In principle I could cover all the coordinates that are possible on a tire, but use different tires for each experiment rather than the same tire.
Would I conclude with the hundreds, thousands of experiments from this that 100% of the tire surface isn’t needed? No. But that’s pretty much the way you framed the argument. A more legitimate approach for the advocates of the 90% junk view is to knockout simultaneously 90% of what they believe is junk and see if the organism actually lives.