The title concerns me a little: Dirty Genes: A Breakthrough Program to Treat the Root Cause of Illness and Optimize Your Health. The author is Dr. Ben Lynch, a naturopath who for about a decade has been studying the effects of genetics and epigenetics on chronic disease, and susceptibility to disease in general. He developed a "Clean Genes Protocol" people can use who want to improve their health.
So, what is a "dirty gene", and how can dirty genes be "cleaned"? The reason we are all different from one another is that there are very slight genetic variations in all genes. There are numerous variants of every gene. The variants for a particular gene are called alleles. The differences among alleles are mostly in the small numbers of SNPs that each gene contains. We'll look at SNPs later on.
We can use eye color as an example. When I was young I learned the Mendelian explanation of inheritance for brown eyes and blue eyes. Somewhere in the genome is a gene with a few common alleles (variants) that controls eye color; call it BrownEye. One allele makes eyes brown by coding for a protein that produces the brown pigment; call it BrownEye+. Another allele makes eyes blue because it codes for the same protein in a form that won't operate correctly, so the pigment is not made, and the natural blue iridescence of the iris is seen instead; call it BrownEye-. These two sentences explain why brown eyes are considered dominant: We all have two copies of each gene. If someone has two copies of the same allele, of course their eye color will be the expected color, brown if the two copies are BrownEye+ and blue if the two copies are BrownEye-. What happens when someone has one copy of each allele? The BrownEye- allele produces a "broken" protein that can't produce pigment, but the BrownEye+ allele produces a working protein, so the pigment is made anyway; thus, that person will have brown eyes. Caution: this is very simplified. More than one gene is involved, and there are several kinds of "brown", plus "green" and "hazel" eye colors.
I don't know what it is that is different between these two alleles of BrownEye. There are several kinds of mutations, changes in our DNA, and we each accumulate a few hundred new mutations in the DNA of every cell in our bodies in our lifetime. The average rate is about 65 "per generation", based on a statement in this Wikipedia article. I presume that a "generation" is the 20-40 (average 33) years between our birth and the age at which we typically reproduce. We continue to accumulate mutations after that, but none of those are going to be found in our descendants.
Remember, we have two copies of our entire genome in each cell. By far the most common mutation—which can be caused by cosmic rays, environmental toxins, and the "stumbling" that the DNA copying machinery does on occasion—is the SNP. This means that, at the age we usually reproduce, each egg or sperm cell in your gonads will differ in about 33 locations from the DNA you were born with, and 90% of those will be SNPs.
Dirty Genes is all about SNPs, considering those that cause our DNA to operate different from the "optimal genome" (my term) to be "dirty"; the author doesn't say what kind of SNP is "dirty", not in any useful way. I think he is really writing about alleles, but there can be many more than the two I posited above, even for something "simple" like eye color.
With this lead-up, we can get a bit more practical. Getting your whole genome sequenced now costs something over $1,000, compared to the few billion dollars spent to produce the first total sequence. If you were to get your whole genome sequenced, and that of one of your parents or siblings, you would find on average about 10 million SNP differences between the two of you, scattered somewhat clumpily throughout each genome.
A SNP is a "single nucleotide polymorphism". A nucleotide is a 3-codon (3-"letter") sequence such as AGC. If in a particular place you have AGC and your father has ACC, that "G" is the SNP. This may or may not cause trouble for one of you. The following diagram will help:
The coding DNA, the DNA that is used to make proteins, totals about 1.2% of the whole. So it contains at most 1.2% (probably somewhat less) of all the SNPs, or 120,000.
Regulatory DNA, that performs functions such as controlling the rate a particular gene produces protein, totals about 8% of the whole. So the number of SNPs found there adds up to another 800,000. The number of SNPs that can potentially "do something" is thus a little under one million. This squares with a statement by the author that we all have "a million" SNPs. But he doesn't explain it like I just did.
Now look at the diagram. We have to consider the section headed "coding region" to actually refer to coding DNA and regulatory DNA, or 9.2% of all our DNA. The "transfer table" used to convert DNA codons to amino acids in proteins has 64 codes. Three of these are used for start or stop (I think there are 2 "stop" codons). For the rest, 61/20 (there are 20 amino acids) is just over 3, and it means that the average amino acid has 3 codes that will request it in a pending protein synthesis.
A SNP that codes for the same amino acid as the DNA without that SNP is considered a "Synonymous" mutation. The protein isn't changed. So we can put 66% on the "Synonymous" box above, and 33% (or 34%) on the "Non-Synonymous" box. Below that, "Missense" means that the amino acid in the "different" protein will allow it to operate, but perhaps differently, while "Nonsense" means either that the "different" amino acid in that location will cause the protein to fold wrong and not work at all, or that the codon is a premature "stop" and the protein is cut short. "Nonsense" is more rare than "Missense", but I don't know by how much.
It comes down to this: About 300,000 of the SNPs in your DNA make it operate differently from whatever might be considered "optimal" or "standard". Since the actual distribution of SNPs is biased toward non-coding DNA, the number will be less. We have something over 20,000 coding "genes", maybe as many as 23,000. Each of them, then, contains a few SNPs; the average is about 14. So looking back at our BrownEye gene, the broken pigment that produces blue eyes is probably due to only one of the SNPs.
I infer that a "dirty gene" is one that has a Missense or Nonsense SNP, as compared to the "optimal" gene. Dr. Lynch is concerned with a combination of diet, exercise and other habits that support the proper operation of genes, as much as is possible based on the SNPs they contain.
The second genetic theme in the book is the methylation process that our cells use to actually accomplish gene regulation. Methylation is not yet well understood. It accounts for changes in gene expression; in particular, for example, the thousands of genes in a liver cell that are not needed for liver function are deactivated by being "coated" with methyl groups so they cannot be "reached" by the protein-producing machinery. Various levels of methyl "coating" are used for more fine regulation, such as the timing of certain proteins when they are needed or need to be temporarily slowed down or shut down. This is controlled by many of the "things" (we can't call them genes I suppose) that the regulatory 8% of your genome contains.
SIDEBAR: Hmm, I have seen the term "regulatory sequence" in a number of articles, and two abbreviations that may be synonyms: "regseq" and "refseq". These are both also used as software abbreviations, though, so I'll temporarily use "RS" for any of the "things" in the regulatory DNA.
The author's explanation of SNPs and "dirty genes" is directed quite differently from the above. I guess I expect more intelligence in those who read this, compared to his expectation for those who read his book.
Now I have to pan it. Ten years is a long time, and Dr. Lynch has given this a lot of effort, but he is up against a huge and hugely complex subject. What I think he has really done is to take the menu of recommendations that naturopaths have used for decades and give it a "new and improved" explanation with new buzz words. But certain fundamental knowledge is dramatically lacking. I'll pick one example that struck me early on.
No matter who you are, the Clean Genes Protocol begins with eliminating certain foods. Among them is gluten. This in spite that it is well known that only 1% of people suffer celiac disease, and thus cannot eat gluten. My former supervisor is one such, so I am familiar with it. Curiously, every time but one that gluten is mentioned in the book, it is a forbidden food. That one time, he throws a sop, telling us that one of his sons isn't bothered by gluten, but that he and the other son are very bothered by it. The term "celiac" is nowhere found in the book. That is shocking. Inexcusable.
A second example: The SNPs in a gene called the "methylation master gene", called MTHFR, are stated as a cause of Down Syndrome, along with a laundry list of lesser problems. Down Syndrome is caused by a very different kind of mutation, an extra Chromosome 21. I suppose you could call that 120 million SNPs. This is beyond belief!
I was only on page 24 when I saw that. I didn't read in detail much farther. I began to go through some of the recommendations—and found the gluten bungle—to see if it all might still make sense. It does not.
Compared to the recommendations of most naturopaths, the advice is actually a bit watered down. Though it is a fairly big book, he is trying to simplify the actual advice. But the reasons he gives for the recommendations do not make sense. "Dirty genes" is a catchy term. Maybe some day someone will define it more appropriately. But what is being "cleaned" from these "dirty genes"? Methyl groups. And you know, that is actually true, for the most part. The trouble is, this all has limited application. It is nowhere near as fine tuned as he claims.
The book is repackaged naturopathy with a shiny, new explanation for why things work or don't work, but the explanation doesn't explain enough. Our knowledge of the genome, the RS package (the "regulome"?), the proteome (all our proteins), and the saccharome (the different types of cellular sugars and simple carbohydrates, that outnumber proteins 20:1 or more), is very, very early and incomplete. Furthermore, instead of producing steps tuned to each individual's needs, the book's advice contains far too many broad brush recommendations will cause the majority of people to refrain from doing or eating things that don't matter, or that are perhaps better for them than not. In this case, a little knowledge can be quite a danger, indeed.
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