Re: Junk DNA fraction and mutational load

On 2/7/2025 9:01 AM, Kerr-Mudd, John wrote:

On Thu, 6 Feb 2025 13:49:48 -0600
RonO <rokimoto557@gmail.com> wrote:
 

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.
>

It's a mess. But one that (just about) works, not a very good Design,
then.
 

Transposons and retrovirus are very efficient selfish genes.  They take Dawkins' proposal to the extreme.  They use living cells and their replication of their own genomes in order to insure the propagation of their DNA sequences.  Some lifeforms like Fugu have greatly limited their replication, but most lifeforms have not been that successful. Birds (dinos) were more efficient than mammals at reducing transposon activity.  The chicken genome is only 40% the size of the human genome with a lot fewer transposon sequences.  When the number of sequences in genebank was minimal in the old days you could use BLAST to look for CR1 sequences (transposon chicken repeat one).  It would give you matches down below 45%.  The old hybridization data that repetitive and single copy sequences were based on would not have identify matches with these short sequences 250 to 300 bp (the major CR1 sequence the intact transposon is over 3 kb, but it leaves shorter footprints where it has been, that may themselves be transposable using the genes of the full CR1 sequence).  My take is that most of what is considered to be single copy sequence in the genomes is just old transposon sequence.
Dinos and their ancestors were likely able to restrict the replication of transposons and maintain a smaller genome size.  Indels are supposed to occur at the same rate as single nucleotide mutations, and if the deletions did not involve coding sequence they would not have been selected against.  My take is that birds restrict transposon activity enough to maintain a smaller genome.  This has allowed them to maintain shorter introns as well as a smaller genome.
Ron Okimoto