Comment by uh_uh

Of course there is bias, the bias is provided by the natural environment where the organisms coded by the genome must thrive or die. The bias is applied after the mutation occurs, but the mutations themselves are random, or nearly so. Probably there is some differential rate between the likelihood of each of the four base pairs to mutate into each of the others, but I would guess its nearly parity, because that would probably be close to optimal (though that depends on the details of the genetic coding scheme, ie the triplet code that translates nucleotide triples into amino acid codons).

Only a tiny percentage (around 1%) of the DNA in chromosomes codes for proteins.

And yes, certain mutations are favored precisely because of the chemistry constraints (an extremely basic one is which base pair changes actually alter the resulting protein; a more sophisticated one is which amino acid changes alter the physical functionality of the protein).

There are multiple constraints that I can immediately identify. Maximal temperature extremes, barometric pressure, atmospheric/substrate compositions, etc. The bias is inherent to the history of the planet Earth and the gradients present across that time and space. I'd say it's highly constrained.

You're choice of samples is rather skewed towards ones sharing a relatively recent common ancestor. Octopus and Sea Squirts are also animals, and they don't have legs or torsos or, in the later case, heads or eyes. Octopus brains are also rather different from those of vertebrates, and they have 8 mini-brains for more distributed/localized control of each major limb.

That said, I agree with you that there is a lot of commonality in life. Even in the case of Octopus we share a lot of DNA. I just mostly think that is due to common ancestor and common environmental pressures, not to some fundamental limit in the breadth of evolutionary potential itself. Its probably worthwhile to wonder at how that actually works though. Maybe evolutionary potential could be improved.

Your maths doesn't seem right. You can estimate mutation rates very easily, and you don't end up at crazy numbers. The sequence space explored by evolution is tiny compared to the possibilities and closely interlinked. A simple example is comparing haemoglobin sequences from different animals.

> If you calculate the pure combinatorial distance between the DNA of 2 species, you must find that you can't just brute force your way from one to the other before the heat-death of the universe.

Can you expand on this? I'm not seeing why it is implausible for one genome to mutate into another, that seems like it could be accomplished in reasonable time with a small, finite number of mutations performed sequentially or in parallel. After all the largest genome is only about 160 billion base pairs, and the average is much smaller (humans are 3 billion base pairs). So what's the difficulty in imagining one mutating into another?

When people say /I'm not (.*?), but (.*)/, they invariably are what they're claiming they aren't. That's what that phrase means. For example, we've all heard it a million times from people defending their vote for Donald Trump. There's even a wikipedia page about it:

https://en.wikipedia.org/wiki/I%27m_not_racist,_but...

If you really mean $2, then just say $2, you don't have to preface it with "I'm not $1, but". That's a waste of words, beating around the bush, a rhetorical shield, that reveals that you really are $1 and you feel the need to be defensive about it.

The word "but" in that context means the thing before it is false, just air escaping from the folds of your fat, and you can ignore everything before the "but".

"But" is a contrastive conjunction, signaling the clause before "but" is expected, socially required, or reputationally protective, and the clause after "but" is the actual communicative payload. It means to discount or ignore $1 and evaluate the speaker by $2. Saying “I’m not $1, but $2” does not strengthen $2, it does't make $2 safer or clearer, it just signals defensiveness, and undermines credibility.

Again, this is a discussion about psychedelic mushrooms, fairytale-like hallucinations, and machine elves, so woo away all you want!

https://www.youtube.com/watch?v=aO2dPIdEaR4

In stark contrast to what you're claiming, I have absolutely zero patience for intelligent design and the likes -- that’s exactly my point.

All I'm saying is that the whole point of the theory of evolution is that blind enumeration of mutations is not required, and that combinatorial feasibility emerges in spite of the vastness of the search space. It is already well known that mutation bias exists, so none of this is controversial.

Multiple commenters here have already explained this from different angles, including chemical and environmental constraints (PaulDavisThe1st), developmental and functional constraints (Supermancho), and even software analogies like coverage-guided fuzzing and genetic algorithms (BobbyTables2). These are not fringe ideas; they are standard ways of explaining why your "astronomical search space" framing is a strawman.

You are hedging; I am not trying to weasel word or distance myself from evolution, or use red-flag rhetorical "I'm not $1, but $2" devices. I have read, agree with, and acknowledge the other replies to your message, because I understand that evolutionary theory already fully explains the concern you're raising.

Your claim that "blind enumeration of mutations seems combinatorially infeasible due to the vastness of the search space" flatly contradicts the theory of evolution.

This has also been directly challenged by other commenters asking you to justify the alleged combinatorial barrier in concrete terms (uplifter), and by others pointing out that genomes do not need to traverse all possible combinations to move between viable states.

The entire point of evolutionary theory is that blind enumeration is not required, and that combinatorial feasibility emerges from selection, heredity, population dynamics, and cumulative retention of partial solutions. No "woo" is required.

Evolution is blind with respect to foresight, but not blind with respect to feedback, structure, or retention.

Mutation bias, developmental constraints, and non-uniform genotype–phenotype mappings are foundational components of modern evolutionary biology, not ad-hoc patches.

People who doubt evolution tend to rephrase it into a strawman -- "random bit flips over an astronomical search space" -- and then declare that strawman implausible.

Several replies here explicitly reject your framing. For example, thrw045 points out the massive reuse of structural templates across species, and PaulDavisThe1st notes that only a small fraction of DNA even codes for proteins, further undermining the idea of a uniform, unconstrained search.

Your "I'm not pushing intelligent design, but evolution seems combinatorially infeasible" move closely mirrors the Discovery Institute / "teach the controversy" pattern: disclaim ID, then introduce a doubt-claim based on a strawman of evolution as uniform random search, then retreat to "just asking questions." That strategy is explicitly, insincerely, and unintelligently designed to manufacture doubt about evolution while insisting it is not religious.

https://en.wikipedia.org/wiki/Discovery_Institute

We can see the sealioning pattern play out here in real time: repeated insistence that ID is rejected, followed by reiteration of the same mischaracterized impossibility claim, even after multiple substantive explanations have already been given.

I’m not hedging like you are here: evolutionary theory does not claim "blind enumeration over an astronomical space," and treating it that way is simply a misstatement of the theory.

I think I and other people recognize your rhetorical patterns and misunderstandings, even if you don't, thus the downvotes. Other commenters have fully addressed your doubts about evolution. To me, the big give-away was your "I'm not $1, but $2" wording.

In any case, this is a thread about psychedelic mushrooms and hallucinations, so if some machine elves want to weigh in with some woo about population genetics, I suppose that’s fair game.

1) No one asked why it's being down voted (to... -1, the horror). I'm not here for internet points.

2) This isn't my field - I am not making any claims, merely relaying what I thought was an interesting concept/mechanism I hadn't heard of before, that I thought other curious individuals here might also think was interesting. Isn't that the entire point of HN? I would have very much appreciated links or something to Google over this bizarre analysis of why my comment is downvoted. I didn't know this wasn't novel and was accepted science.

3) I understand Bret/Joe aren't looked upon favorably by certain crowds, particularly on this forum. I tried to get ahead of the "but didn't you know they can't be trusted!" comments and attempt to focus on the substance. If the substance is wrong, great! Let's talk about that.

4) You are assuming malice where there is none, and calling me disrespectful and insisting I must know things. I find that quite disrespectful and uncalled for. Not everyone has your opinions or knows what you know. 10k a day and all that https://xkcd.com/1053/

HN guidelines: "Please respond to the strongest plausible interpretation of what someone says, not a weaker one that's easier to criticize. Assume good faith."