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In a youtube video by an evolutionary biologist titled Creation Myths: Genetic Entropy at 14:50 he explains that the ratio between beneficial + neutral mutations and deleterious mutations decreases over time since the probability of a beneficial mutation increases over time because the more deleterious mutations the more opportunities for a deleterious substitution to back mutate creating a beneficial mutation until there is an equilibrium.

My issue with this is that this model only includes substitutions and according to one study 16% - 25% of mutations in the human genome are indels. And the probability of a indel reversing is incredibly low as far as I understand. What I would like to know is how does indels and other mutations beyond substitutions affect this model of mutations? Surely it shouldn't be ignored.

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    $\begingroup$ On the contrary, stepwise mutation (adding/subtracting one unit from a repeat array) is one of the canonical mutational patterns for indels, and it is eminently repeatable/reversible. And 25% is probably too low! $\endgroup$
    – Maximilian Press
    Commented Nov 8 at 20:24
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    $\begingroup$ @MaximilianPress I agree with answer $\endgroup$
    – M__
    Commented Nov 8 at 22:33

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Hugely complex question. It has been considered and reconsidered many times. There is the neutral theory, which states that the vast overwhelming majority of mutations have no effect on the phenotype. The nearly neutral theory and the classical theory. Neutral theory is a big subject.

On indels, these can be "neutral" and reversing depends how much selection pressure they are under. Microsatellites do "reverse".

Essentially, this is a massive question and its better to consider a single species as an example for a single type of mutation

See the comment by @MaximillianPress. That is a good answer, the step-wise mutation model is not a bad model for (microsatellite indels) and states indels can "grow" and "shrink" one repeat unit at a time. I know what the OP is saying alot of indels occur in protein genes and must have a specific function.

Indels under selection pressure are common in the surface antigens of many pathogens including HIV. The distribution for codon indels in env was modelled by Fletcher and Yang 2009 here. This is a strongly skewed distribution and maintenance of very long indel lengths of up to 100 could only be maintained by selection pressure, however the preponderance of small copy number indels is massively dominant.

The stepwise model (SMM) is not a skewed distribution it assumes that there is equal probability for increasing the indel size as it is reducing it. This was used for microsatellites which are assumed to be neutral (not under selection pressure).

In protein modeling under the old DUET model (now deprecated) by Pires and Tom Blundell 2014 showed maximum structural disruption for indels.

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  • $\begingroup$ Can you elaborate on how indels are able to be reversed? Or do you just mean reversed as in taken out of the gene pool due to selection? $\endgroup$
    – Shannon T
    Commented Nov 19 at 9:05
  • $\begingroup$ done as requested $\endgroup$
    – M__
    Commented Nov 19 at 12:50

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