Human mutation rate is way too high for evolution to occur

A few years ago the Junk-DNA theory rescued the evolutionary theory - Today: THERE IS NO JUNK-DNA!

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570035/

Excerpt: "For the human population to maintain a constant size from generation to generation, an increase in fertility must compensate for the reduction in the mean fitness of the population caused, among others, by deleterious mutations. The required increase in fertility due to this mutational load depends on the number of sites in the genome that are functional, the mutation rate, and the fraction of deleterious mutations among all mutations in functional regions. These dependencies and the fact that there exists a maximum tolerable replacement level fertility can be used to put an upper limit on the fraction of the human genome that can be functional. Mutational load considerations lead to the conclusion that the functional fraction within the human genome cannot exceed 15%."

https://www.livemint.com/Science/OyB7ydFTcUZOpcXcVmBlpK/Scientists-say-75-of-human-gene-is-junk-DNA.html

Excerpt: "Researchers from the University of Houston in the US found that the functional portion of the human genome probably falls between 10% and 15%, with an upper limit of 25%."

https://futurism.com/new-study-shows-that-only-about-25-of-our-dna-is-functional

Excerpt: "Graur found that even if the rate of deleterious mutation was very low, birth rates would need to be unrealistically high to sustain the population if 80 percent of the genome were functional. As reported by The University of Houston:

"For 80 percent of the human genome to be functional, each couple in the world would have to beget on average 15 children and all but two would have to die or fail to reproduce…If we use the upper bound for the deleterious mutation rate (2 × 10−8 mutations per nucleotide per generation), then … the number of children that each couple would have to have to maintain a constant population size would exceed the number of stars in the visible universe by ten orders of magnitude."

 https://sites.google.com/site/georgiatiptonbzb210assessment/genetic-load

Excerpt: "For humans, the mutation rate is predicted to be approximately 70-150 mutations per generation, much higher than the limit that was proposed earlier. 

If this were the case, scientists have calculated that only 1% of functional data was possible, far less than the 80% prediction given by the ENCODE Project.

After further scientific study was undertaken, however, it was suggested that humans may actually be able to withstand more than 1 deleterious mutation per generation. It was thought that they may, in fact be able to withstand between 2 and 10. Using this information, it is estimated that 10% of the human genome would then exhibit an organism-level function, leaving 90% to be classified as junk DNA."

https://www.nature.com/news/2009/090827/full/news.2009.864.html

Excerpt: "Every time human DNA is passed from one generation to the next it accumulates 100–200 new mutations, according to a DNA-sequencing analysis of the Y chromosome."

Modern science reveals that the junk-DNA theory is just wishful thinking

https://www.futurity.org/junk-dna-1728712/

https://www.researchgate.net/publication/269187480_Non-coding_RNAs_Biological_functions_and_applications?fbclid=IwAR2RYi1Zw99F_-87r8sj0Q3z1FqHJQ19dCBHZUwDbSx2jaV4GPsBLO4ThRY

"In addition, there has been an explosion of research addressing possible functional roles for the other 98% of the human genome that does not encode proteins. In fact, >90% of the human genome is likely to be transcribed yielding a complex network of overlapping transcripts that include tens of thousands of long RNAs with little or no protein forming capacity; they are collectively called non-coding RNA."

https://www.myscience.org/news/2021/the_cause_of_genetic_diseases_can_also_be_found_in_gene_deserts-2021-unibas

"The study in the scientific journal Nature shows that a single genetic change in the "junk DNA" long thought to be useless can have serious consequences."

My comment: Every scientist realizes the truth about high mutation rate (mutational load, genetic load) within humans and other organisms, too. The junk-DNA theory was developed in order to the problem of mutational load to be solved. Today, serious scientists admit that there is no junk-DNA in cells of organisms. But the high harmful mutational load remains. Conclusions are obvious: Evolution never happened. Don't get lost, my friends.

Epigenetic on/off switching by cytosine methylation

Methylated cytosines (C) outside CpG islands control gene expression

https://www.sciencedaily.com/releases/2021/04/210416131923.htm

Excerpt: "Based on previous work by a group in Italy, the researchers were confident that CRISPRoff would be able to silence specific genes, but they suspected that some 30 percent of human genes would be unresponsive to the new tool.

DNA consists of four genetic letters -- A, C, G, T -- but, in general, only Cs next to Gs can be methylated. To complicate matters, scientists have long believed that methylation could only silence genes at sites in the genome where CG sequences are highly concentrated, regions known as "CpG islands."

Since nearly a third of human genes lack CpG islands, the researchers assumed methylation wouldn't switch these genes off. But their CRISPRoff experiments upended this epigenetic dogma.

"What was thought before this work was that the 30 percent of genes that do not have CpG islands were not controlled by DNA methylation," said Gilbert. "But our work clearly shows that you don't require a CpG island to turn genes off by methylation. That, to me, was a major surprise."

Epigenetic Inheritance Enhances CRISPRoff's Therapeutic Potential

Easy-to-use epigenetic editors like CRISPRoff have tremendous therapeutic potential, in large part because, like the genome, the epigenome can be inherited.

When CRISPRoff silences a gene, not only does the gene remain off in the treated cell, it also stays off in the descendants of the cell as it divides, for as many as 450 generations.

To the researchers' surprise, this held true even in maturing stem cells. Though the transition from stem cell to differentiated adult cell involves a significant rewiring of the epigenome, the methylation marks deposited by CRISPRoff were faithfully inherited in a significant fraction of cells that made this transition.

These findings suggest that CRISPRoff would only need to be administered once to have lasting therapeutic effects, making it a promising approach for treating rare genetic disorders -- including Marfan syndrome, which affects connective tissue, Job's syndrome, an immune system disorder, and certain forms of cancer -- that are caused by the activity of a single damaged copy of a gene."

My comment: Old dogmas are upended again. This discovery emphasizes the role of epigenetic mechanisms and factors in DNA transcription and minimizes the role of the DNA in these cellular processes. This research also confirms that epigenetic changes might be very robust and long standing, even over 450 generations. DNA methylation patterns affect both transcription and alternative splicing procedures so it's one of the most significant factors influencing organismal adaptation and even speciation. However, changes in methylation patterns never result in any kind of evolution. Don't get lost, my friends.