Re: Junk DNA fraction and mutational load

On 1/28/2025 7:47 AM, Kerr-Mudd, John wrote:

On Tue, 28 Jan 2025 18:25:40 +1100
MarkE <me22over7@gmail.com> wrote:
 

Dan Graur has argued that for purifying selection to prevent mutational
load runaway, the functional fraction of the genome must be constrained
(to 10-15%?).
>
If the mutation rate was halved, would the allowable functional fraction
double? Or is it not that simple?
>
I posted a comment on Sandwalk criticising the latest Long Story Short
video's treatment of the c-value paradox:
https://sandwalk.blogspot.com/2025/01/intelligent-design-creationists-launch.html
>
I also posted a query on this paper which argues against Graur's
conclusion: "Mutational Load and the Functional Fraction of the Human
Genome"
https://academic.oup.com/gbe/article/12/4/273/5762616?login=false
>
Larry Moran responded with "Graur refereed that paper and he now agrees
with the general conclusion that the mutation load argument does not put
a severe constraint on the fraction of functional DNA in the human genome."
>
Is this now generally accepted?
>
Note though the paper referenced has this conclusion: "We stress that
we, in this work, take no position on the actual proportion of the human
genome that is likely to be functional. It may indeed be quite low, as
the contemporary evidence from species divergence and intraspecies
polymorphism data suggests. Many of the criticisms of the ENCODE claim
of 80% functionality (e.g., Doolittle 2013; Graur 2013) strike us as
well founded. Our conclusion is simply that an argument from mutational
load does not appear to be particularly limiting on f."
>

  How does this help god the designer - he's preloaded DNA with junk,
maybe more, maybe less. Not a very good design is it?
 

The existing rate of mutation does not limit the existing amount of functional DNA sequence to anywhere near the amount of existing functional DNA (functional DNA is a small fraction of the genome in humans).  Life has been adapting to transposons and retrovirus for likely a couple billion years.  My guess is that around 85% of the human genome is composed of transposon and retroviral sequences, most of which is so old that you can no longer tell that it was once transposon sequence.  The rest is functional genes, regulatory sequences and bits of pseudogenes that likely got inserted back into the genome as mRNA by retroviral replication machinery.
One use for junk DNA is to soak up transposon and retroviral activity. With so much of the genome likely due to old transposable elements when one jumps to a new location it is more likely to hit old transposon sequence rather than a functional gene.  I recall early on that heterochromatin composed of satellite DNA (long stretches of short tandem repeats) had evolved and were constantly regenerated in order to remove transposons from the genome.  When a transposon jumps into a short tandem repeat the repeat region is not stable and the transposon is quickly lost (recombined out) of the genome.  Life forms like humans have evolved mechanisms to suppress transposon replication.  When this suppression is lost you observe it as a high rate of knockout gene mutations, and decreased hatch rate in species like Drosophila.  So the existing transposons could contribute to the mutational load, and likely push an organism over the threshold if they went out of control.
10% of the human genome is composed of ALU transposons.  Most of these sequences are so old that they have accumulated knockout mutations and they are no longer functional transposons, but there is still enough functional sequences so that a lot of the dominant gene knockout human live births are attributed to transposon activity.  If the transposition was no longer suppressed we would likely be doomed.  So the current mutation rate can be handled by the existing amount of coding sequence, but the rate of mutation can be increased quite a bit by just losing the suppression of the transposition events.
Ron Okimoto