"No soup for you" - Charlie, random mutations are sparse for Neo-Darwinism

Neo-Darwinism depends upon "random" mutations to make a new phenotype (form). 

SNP or Single Nucleotide Polymorphisms are the primary mutations neo-Darwinism relies on. They are point mutations that cause a single nucleotide change, of which there are four, A, T, C, and G. (above). These mutations, in theory, make new phenotypes for natural selection to operate thus fixing this mutation in the genome.

These authors recognize that there is such a small number of them that they do not explain human evolution or disease. If SNP's don't account for disease (a different phenotype), how do they cause a distinct evolutionary phenotype?

They suggest there are other factors at play.

As we will discover, these factors are epigenetic ones. 

The author's state:

(2002-pre-epigenetics)

"SNP alleles in human disease and evolution"

"In two randomly selected human genomes, 99.9% of the DNA sequence is identical.

The remaining 0.1% of DNA contains sequence variations.

The most common type of such variation is called a single-nucleotide polymorphism, or SNP

These variations are associated with diversity {evolution} in the population."

Although these studies have provided insight into the nature of human sequence variation, it is unknown at present {if they cause disease or evolution}.

Therefore, it is likely that sequence variation alone is not sufficient {to explain evolution or disease}."

The authors point out that SNP mutations should correlate with different diseases.  And that just as diseases are different phenotypes so we should see SNP mutations cause different evolutionary phenotypes. But this was not the case.

This study dismissed 40 Years of population genetics, which sought to correlate SNP's with phenotypic changes in organisms.

As an aside, there's big money to be made with Big Pharma. Lives are on the line. 

Medical researchers in this area are not going to prosecute whether Darwin was right or wrong; they're simply going to get down to the "nuts and bolts" of what is going on. 

Medical undergraduate studies of evolution and genetics did not serve me well as well as many of them.

However, ivory tower researchers are still hanging on to Darwin.

 I recall Bill Murray in Ghostbusters after losing their University position. "You do not know what it's like to work outside of the University, they expect results."

Another type of mutation is called epi-mutations.

Epimutation is an unfortunate term as no nucleotides are "changed" or mutated. Instead, epigenetic "tags" are placed on the wrong CpG sequences in the DNA.

Methyl "tags" are put on the DNA (cytosine, C-M) to alter gene expression usually. Sometimes the tags are placed in the wrong location on cytosines in the DNA. These epigenetic markers can interfere with the correct gene expression. They can cause such diseases as cancer or even aging.  Just about every illness is affected by these "epimutations." 

We are rapidly discovering these epimutations in just the last five years. 

We are in the Golden Age of Medicine. Cancer cures, as well as even life expectancy, will likely be changed.

These cytosine methylations do not change the DNA sequence. As well, they occur by specific enzymes and are not random. As such, they do not follow under neo-Darwinism

As you can imagine, the neo Darwinists are somewhat disappointed at this point. The SNP mutations did not yield much. 

And epimutations are not under non-Darwinism. How can they keep their theory alive?

Well, there's one last hope, and that resides in the CpG portions of the DNA. 

CpG nucleotide pairs are spread all through the DNA. They are the sites for epimutations as well as normal C methylations (epigenetics) for regular gene expression. However, another change (mutation) can occur there.  

When cytosine has an epigenetic tag (methyl group), it has a different conversion rate to another nucleotide, thiamine, C>T.

These, however, are not random "mutations" as required by Neo Darwinism. Instead, these "changes," not mutations, are "specifically" directed. 

They are a mechanism by which specific genes are turned on or off. And their expression can persist through continuing generations. The DNA remains stable over thousands of generations.

In contrast, epigenetics are tags that can be replaced and removed do not permanently change the DNA.

With normal epigenetics, cytosine methylation (C-M) can be passed on to three to four generations (sins of the father to the third and fourth generation) and, in some cases, hundreds of generations (showing love to a thousand).

However, with C to T changes (C>T), these can go on indefinitely. The exact role of these is currently being discovered.

Again this is not neo-Darwinism which works on random mutations. This mechanism works on "pre-existing" genes not derived by NeoDarwinism. 

These C>T epigenetic-related "mutations" (changes) are made by "nonrandom" changes in the DNA.  A methyl group is placed on a C then converted by a "pre-existing" enzyme from C>T. Nothing random here. It's an enzymatic reaction.

This article discusses these issues.

"Genome-wide patterns and properties of de novo mutations in humans"

2015

"Mutations create variation in the population, fuel evolution.

Here we analyze 11,020 de novo mutations from the whole genomes of 250 families.

We show that de novo mutations in the offspring of older fathers are not only more numerous

Functional regions exhibit higher mutation rates due to CpG dinucleotides."

If C>T changes were random mutations per neo-Darwinism, you would expect these mutations or changes to be even throughout the DNA in different sexes and species. 

However, as is this paper shows, C>T changes are moderated both by age and by sex; therefore, they are not random.

Sadly neo-Darwinism is left with little to act on.

SNP's do not correlate well for either disease phenotypes or evolutionary ones.

Epigenetics does not change the nucleotide sequence required by NeoDarwinism.

And the C>T "specific" changes are not random mutations either.

Sorry Charlie (Darwin), maybe something will be found later.

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