Every genetic mutation that could exist, does exist | Hacker News Reader

Every genetic mutation that could exist, does exist

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Single-point mutation. I know the author thinks that leaving out that qualifier makes the claim sound cooler, but it doesn't. It makes the claim sound wrong. Because the unqualified claim is wrong. There are a lot more things in this world than single-point mutations.

What is a single-point mutation?

I beleive this is referring to a single base pair changing in the DNA. SNP (Single Nucleuotide polymorphism)

https://medlineplus.gov/genetics/understanding/genomicresear...

https://en.wikipedia.org/wiki/Single-nucleotide_polymorphism

I think the author took the frequency of changes in SNPs and the human population and figured if the change is "compatable with life" it exists in the human population which is a staggering 8 billion.

There are studies called GWAS (Genome Wide Annotation Studies) where they look at a the genetic sequences of a large group of people and try to figure out if a particular SNP causes a particular issue.

https://medlineplus.gov/genetics/understanding/genomicresear...

This GWAS study for example looked at 5 million genomes to find snps associated with height. "Their analysis revealed 12,111 common single nucleotide polymorphisms (SNPs), or places in the genome where a single letter varies, that were associated with height. "

https://www.broadinstitute.org/news/largest-genome-wide-asso...

An A is replaced by a T, or by a G, or by a C, or vice versa.

The more expansive side of the coin are indels or CNVs (copy number variations), where pieces of genome are replaced by other pieces (ATGCT by ATGCTCTA for example) or just deleted, or where specific pieces are copied a few times. These are far harder to measure using current sequencing technologies; most people still use the ubiquitous Illumina machines which can go up to 300bp, and we know many of those more complex mutations are longer than that.

Another qualifier: "viable". Every viable single-point mutation. This may seem obvious and covered by the "could exist", but it does mean that for any given base pair you won't necessarily find somebody in the population with a mutation there as the claim would seem to suggest.

Clarifying the headline: Every mutation of a single nucleotide of the human genome that could exist likely does in the human population. Just statistically this is very likely if not certain.

His second line of “but all the beneficial ones haven’t had time to become ubiquitous” reveals a weird misunderstanding of how evolution works. Not all beneficial mutations would necessarily ever become “ubiquitous”. And few if any mutations, especially on the scale of a single nucleotide, could fairly be characterized as objectively and universally “beneficial”. Environment and context is crucial.

Take the example of sickle cell disease, which can be caused by a single nucleotide mutation. It can cause many problems in its sufferers but it can also confer its carrier with resistance to malaria. Whether its a beneficial mutation depends entirely on the environment, from prevalence of malaria to availability of treatment for the various symptoms.

To add, the set of observable mutations (beneficial or not) that occur as a result of a single point mutation is in all likelihood an extremely tiny subset of the set of all observable mutations - even after “deduping” for the observed effect.

Thanks for mentioning this. It is about context. The combination of random mutation + environmental context gets misconstrued as pseudo-intellectual design, or propagates an errant belief in a premiere universal set of genetics.

For example, we cannot even truly estimate the number of species of life on the planet, each of them showing their own specific genetic makeups to handle differnt situations, but the tweet only mentions the human genome.

I don't understand something: I was taught that mutations are random, not even predictable (the latter comes from Stuart A. Kauffman book that I've read recently). How did they construct the set of "all possible mutations"? Do we even know enough on chemistry / physics level to make such claims?

Human DNA has ~3 billion base pairs, and each base pair could be switched to one of the other 3, so there are 9 billion possible single-change mutations. With 8 billion people, most having multiple mutations, most mutations exist.

So it's not the set of all possible mutations, just single base pair ones.

>With 8 billion people, most having multiple mutations, most mutations exist.

Not saying that this isn't the case, but the conclusion doesn't derive from those premises alone though.

The fact that number of people > possible mutations, or even that people have more than one each, is not enough. There could be a trillion people and still the total sum of mutations seen be a tiny subset of the 9 billion possible mutations.

The missing element is about the distribution of the mutations, whether all are equally likely or at least or are possible to arrive at, and so on. E.g. the premises could very well hold, but some compounding factor could push towards a subset of them appearing, etc.

Good point. Some mutations cause the sperm, egg, or fetus to be unviable, so those are definitely underrepresented in the population.

Perhaps it's still a useful heuristic for the purposes of rejecting a claim like "Some single mutation might cause 200 IQ and super-strength".

>How did they construct the set of "all possible mutations"?

Just a note, the outcome of a dice roll is also random, but the set of all possible roll outcomes of a dice is known, it's: 1, 2, 3, 4, 5, 6...

But "mutation" includes adding genes (or extending a gene) as well, doesn't it?

I think there's zero humans that have single point mutation that's immediately lethal.

But it should hold true for nonharmful potentially beneficial single point mutations.

So I guess X-Men is not entirely accurate unless they are fueled by more complex mutations.

I have a feeling that being able to control the weather is more complex than a single point mutation.

1. Is this because natural selection isn't driving them out anymore, because modern medicine lets them live long enough to re-produce.?

2. Is this how you get the X-Men?

No, “mutation” doesn’t necessarily mean “bad”. It just means “different than where it was copied from”. Ie the RNA made a copying mistake at some point. If the copy error happens in the creation of egg or sperm cells, then that “mutation” is passed on to the child conceived by those particular cells.

Most of these errors don’t cause any problems so they are just “noise” in the gene pool. The ones that will straight up kill you don’t exist because those children are never born.

Then there are others that are mixed bags and cause stuff like sickle cell disease which causes lots of problems but is prominent in some populations because it also confers resistance to malaria. And then there’s ones that do things that probably don’t matter much, like changing your eye color or making you slightly taller or more likely to hate cilantro or be lactose tolerant or whatever.

Would someone be kind enough to ELI5?

Human genetic code has limited number of letters. If all people had the same set of letters all people would be identical.

Numerically there's enough people so that each differs from that hypothetical singular human by at least one letter.

Of course there are a lot of caveats to this.

It’s an intentionally misleading tweet.

To simplify, It’s saying, if the genome were a string of some length, for any possible byte b and byte position i, there exists a person whose genome has b at position i. Unlike normal character strings, there are only 20 or so valid characters (proteins) encoded by 3 “bytes” (nucleotides) each. So you’re looking at O(10 billion) values of (i, b) that would still keep the string well-formed in its 3-bytes-per-character encoding.

Most importantly, it’s not saying anything about having some bytes b1 and b2 at the ith and jth positions or any generalization thereof.

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