What are the fundamentals of Genetic Entropy?

[Timothy_Horton]

@PDPrice

Don’t worry, I am learning. I learn from most every exchange.

Do you understand yet why Sanford’s idea is wrong?

[T_aquaticus]

@PDPrice

Here is my grossly oversimplified, yet perfectly accurate to the best of my knowledge, summary of GE, along with some quotations from the literature to show support for each premise:

Most mutations are known to be bad, not good. They damage, rather than helping.

“Although a few select studies have claimed that a substantial fraction of spontaneous mutations are beneficial under certain conditions (Shaw et al. 2002; Silander et al. 2007;
Dickinson 2008), evidence from diverse sources strongly suggests that the effect of most spontaneous mutations is to reduce fitness (Kibota and Lynch 1996; Keightley and Caballero 1997; Fry et al. 1999; Vassilieva et al. 2000; Wloch et al. 2001; Zeyl and de Visser 2001; Keightley and Lynch 2003; Trindade et al. 2010; Heilbron et al. 2014).”

https://www.genetics.org/content/204/3/1225
Fitness Effects of Spontaneous Mutations Nearly Unseen by Selection in a Bacterium with Multiple Chromosomes | Genetics | Oxford Academic

You mentioned that this is accurate “to the best of your knowledge” yet I already showed you that the paper you are citing found something quite different:

Here, we analyzed the fitness effects of 43 lineages of B. cenocepacia that underwent 7 months or > 5500 generations of evolution under greatly limited selection. Direct competitions with the common ancestor were conducted in three environments to quantify effects of different forms of mutational load. Despite the duration of MA, many lineages evidently suffered no fitness decline, as they had selection coefficients that did not significantly differ from s = 0. Given that each lineage accumulated between 2–14 mutations, the most likely explanation for these findings is that the vast majority of spontaneous mutations have minimal effects on fitness across this range of environments.
https://www.genetics.org/content/204/3/1225

On top of that, genomes like those in humans are mostly junk. About 10% of the human genome shows evidence of function. That means the bulk of the mutations occurring in the other 90% are neutral. Most mutations are neutral in the human genome.

@PDPrice

Many scientists have attempted to wave away this fundamental genetic problem for evolution by suggesting that most mutations may be neutral–but this is missing the point because no mutation could ever be truly neutral. Every change you make to the genome will have some effect.

What Sanford need to show is that these mutations have such a large effect that they prevent reproduction or survival.

One of the big assumptions that Sanford makes is treating all slightly deleterious mutations the same. Obviously, this can’t be the case. If that one additional mutation results in sterility or death then that is not a slightly deleterious mutation. It will be strongly selected against. On top of that, if we can’t see a statistically significant difference between populations with a given mutation and populations with a mutation, then how in the world is this going to lead to the extinction of the species?

[PDPrice (Paul Price)]

@T_aquaticus

You mentioned that this is accurate “to the best of your knowledge” yet I already showed you that the paper you are citing found something quite different:

I did bother to read through that paper, and you are misrepresenting their findings. Their conclusion went along with the statement I quoted, not against it. I am not quote-mining.

[PDPrice (Paul Price)]

@T_aquaticus

On top of that, genomes like those in humans are mostly junk. About 10% of the human genome shows evidence of function. That means the bulk of the mutations occurring in the other 90% are neutral. Most mutations are neutral in the human genome.

@Rumraket You asked me to show you who was saying this, and here you go. Here’s just one example.

[PDPrice (Paul Price)]

@T_aquaticus

What Sanford need to show is that these mutations have such a large effect that they prevent reproduction or survival.

You have it exactly backwards. It is the fact that they do NOT prevent reproduction or survival that makes them so dangerous to begin with.

[T_aquaticus]

@PDPrice

I did bother to read through that paper, and you are misrepresenting their findings. Their conclusion went along with the statement I quoted, not against it.

I would be interested in any quotation where the clearly state that deleterious mutations outnumbered neutral ones. The best I can find is them lumping neutral and deleterious mutations together:

By measuring the fitness effects of MA lineages with fully characterized mutational load, we have performed a uniquely systematic study of the rate and fitness effects of spontaneous mutations with known genetic bases, demonstrating that the vast majority of mutations accumulated in B. cenocepacia MA lines are neutral or deleterious for fitness, and that the fitness of individual mutations can be environmentally dependent, even though the general features of the distribution of fitness effects are similar in different environments.

[T_aquaticus]

@PDPrice

It is the fact that they do NOT prevent reproduction or survival that makes them so dangerous to begin with.

Then why does Sanford claim that GE will lead to extinction?

[PDPrice (Paul Price)]

@T_aquaticus

lumping neutral and deleterious mutations together:

That gives away the game. We know from Kimura that most neutral mutations are deleterious (he didn’t even bother trying to graph beneficial neutrals, and only speculated as to their frequency). And we also know (and I quoted) that there are no truly (or as Kimura would say, ‘strictly’) neutral mutations.

[T_aquaticus]

@PDPrice

That gives away the game. We know from Kimura that most neutral mutations are deleterious (he didn’t even bother trying to graph beneficial neutrals, and only speculated as to their frequency).

If Kimura says that most mutations are neutral, then how can he also be saying that they are not neutral but deleterious. You seemed to have confused yourself.

Let’s say we have 100 mutations. 90 of them are neutral, 7 are deleterious, and 3 are beneficial. It would be accurate to say that most mutations are either neutral or deleterious. Do you agree?

[PDPrice (Paul Price)]

@T_aquaticus

If Kimura says that most mutations are neutral, then how can he also be saying that they are not neutral but deleterious. You seemed to have confused yourself.

Read Kimura’s paper where he clearly enunciates a difference between ‘strictly neutral’ and ‘effectively neutral’. You’re missing the distinction. There are no strictly neutral mutations.

It would be accurate to say that most mutations are either neutral or deleterious. Do you agree?

Neutral mutations is an oxymoron. Every mutation has an effect.

[T_aquaticus]

@PDPrice

Read Kimura’s paper where he clearly enunciates a difference between ‘strictly neutral’ and ‘effectively neutral’.

If they are effectively neutral then they can’t cause sterility or death, by definition.

[PDPrice (Paul Price)]

@T_aquaticus

If they are effectively neutral then they can’t cause sterility or death, by definition.

Yes, and one little speck of rust will not cause you to need to go buy a new car.

[T_aquaticus]

@PDPrice

Yes, and one little speck of rust will not cause you to need to go buy a new car.

The last piece of rust that interrupts vital function will be selected against and is not effectively neutral. It is deleterious and is selectable. That’s the problem with Sanford’s thesis. You don’t need to be perfect to be a successful species.

[PDPrice (Paul Price)]

@T_aquaticus

The last piece of rust that interrupts vital function will be selected against and is not effectively neutral.

Of course. But by then your whole population is mostly rusted out. You can’t select away the whole population. Mutations are only selected for or against individually. You can’t just start over with a new genome. If we could then genetic entropy would not be an issue.

[T_aquaticus]

@PDPrice

Of course. But by then your whole population is mostly rusted out.

Apparently, being mostly rusted out has worked for 3.5 billion years.

@PDPrice

Mutations are only selected for or against individually. You can’t just start over with a new genome.

But you can remove deleterious mutations as they arise, especially those that prevent reproduction or are lethal.

[Timothy_Horton]

@PDPrice

Of course. But by then your whole population is mostly rusted out. You can’t select away the whole population. Mutations are only selected for or against individually. You can’t just start over with a new genome. If we could then genetic entropy would not be an issue.

Sanford’s explanation for why GE has allowed life to exist on the Earth for over 3.5 billion years is…?

[PDPrice (Paul Price)]

@T_aquaticus

Apparently, being mostly rusted out has worked for 3.5 billion years.

Or maybe that assumption of yours is incorrect. This evidence says it is.

But you can remove deleterious mutations as they arise

Everything I’ve just showed you here says you can’t. Most mutations are too small to be selected out.

[T_aquaticus]

@PDPrice

Or maybe that assumption of yours is incorrect.

It isn’t an assumption. It is a conclusion drawn from mountains of evidence in the field of geology.

@PDPrice

Everything I’ve just showed you here says you can’t.

Then I would suggest that you go to my thread on pocket mice where this is demonstrated in living populations.

The Rock Pocket Mouse: A Model for Natural Selection

I thought it would be helpful to use a specific example of natural selection for those having issues understanding how it works. Coat color in pocket mice is one of those examples. The paper I will be working from is found here: First, let’s look at the environment where these mice are found. They are found in the southwest deserts of the US, and the vast majority of their range is made up of light brown dirt and rocks. However, there are isolated areas where recent volcanic eruptions have created areas with dark black basalt rock. Interestingly, when we look at the distribution of coat color in pocket mice it matches the environment they are found in: [image] The black mice are found in islands of black basalt rock, and brown mice are found in the sea of brown desert between those islands of volcanic rock. I don’t think it is a stretch to state that camouflage is playing a strong role in the distribution of coat color alleles. The scientists in the paper also looked at in…

It’s even demonstrated in the H1N1 data where the number of fixed mutations is well below the rate at which mutations occur.

[Timothy_Horton]

@Timothy_Horton

PDPrice do you at least understand a mutation can only be judged deleterious, neutral, or beneficial with respect to the effect it causes the organism in its specific environment?

A mutation for longer thicker fur may be beneficial for a cold climate Arctic fox but deleterious for a tropical climate lemur. Capisce?

You’ve shown zero evidence you understand this critical point. What about the concept is so difficult?

[T_aquaticus]

The next question we have to ask is the ratio of slightly beneficial to slightly deleterious neutral mutations. These would be effectively neutral mutations, so we wouldn’t be able to detect whether they are slightly deleterious or slightly beneficial using population demographics. So how do we determine what this ratio is? How did Sanford determine this ratio?

If the tiny effects we are talking about have to do with the number of bases in a genome, then a genome with a stable number of bases where deletions are balanced by insertions would have no net change in fitness. This appears to be the case for our branch of the primate tree, with the gibbon, orangutan, gorilla, and human genomes having nearly the same base count over 10’s of millions of years.

If Sanford really wants to make these grand claims, then we need evidence for the distribution of effects caused by effectively neutral mutations, and I have yet to see it.