Dear Mark: Gene Expression

I received tons of emails from last week’s Gene Expression: Location, Location, Location post. Thanks to everybody for their feedback and questions. In the comment section of last week’s post, Ed was interested in other concrete examples of gene expression (the ability of a gene to produce a biologically active protein). In personal emails, others asked for more explanation of the difference between genes and gene expression. Still others wanted to hear more about the interaction between their gene expression and lifestyle choices. Given the range of reader questions this week, I thought I’d reframe this week’s Dear Mark to include more of an overview of this recurring MDA theme. There’s a lot to be said on the subject, and I promise this post won’t be the last word on it. Nonetheless, there’s no time like the present to give a proper introduction and dive right in.

Let me just say that gene expression is one of my favorite areas of interest, and it’s truly at the heart of the Primal Blueprint. In fact, it’s the real beauty of it as well. It confirms that the day-to-day choices we make have incredible impact. And we can influence gene expression to a far greater degree than anyone ever thought possible.

Everyone has the DNA “recipe” to build a human being. The DNA itself is not really so much a “blueprint” (as many people assume) as it is a recipe. As with all recipes, it allows for a little variation to spice things up and even room for improvement. That means that some ingredients can change a little and you still wind up with the intended result. A little more sugar, a little less salt, an added spice, a lower cooking temperature: the end result still resembles the picture in the cookbook.

We often hear about the computer hardware/software analogy. An analogy I like to use is that of a book and its readings. Your genome itself (your DNA) is fixed and can’t be changed. It is the book itself. Once it’s been written (and in this case each of your 60 trillion cells has the exact same copy of your story), you can’t change the words. But a book, even though it’s fixed, can be read differently by different people. (Imagine three different screenwriters taking the same book and coming up with three very different movie versions). The lines themselves are altered in the context of the interpretation.

Similarly, while your genes are “fixed”, the expression of those genes – the amount of proteins they cause to be made, whether or not they are even switched on or off at all – depends on the “environment,” the circumstances surrounding those genes. Diet, exercise, exposure to toxic chemicals (or fresh air), medicines, even the thoughts you think (which generate actual chemical signals) all influence gene expression – positively and/or negatively, depending on the choice. Eat a diet that is high in sugar, and gene expression moves in a direction that produces more insulin, that shuts off insulin receptors, that down-regulates lipase and other enzymes involved in fat-burning, that increases pro-inflammatory cytokines, etc. When you change to a diet low in sugars and rich in healthy fats, those or other genes are directed to reduce inflammatory expression, down-regulate insulin-producing metabolic machinery, up-regulate insulin receptors and rebuild cell membranes to reflect the presence of better building materials (omega 3 fatty acids, etc.). Research in gene expression is exploding right now and is examining both the impact of environmental factors and the promise of epigenetic therapies. The connection between insulin resistance and genetic expression (particularly in relation to exercise) was raised in last week’s comments. Diet and toxin exposure have been shown to influence gene expression in laboratory studies. Here are a few study abstracts to pique your interest: PubMed 1, 2, 3.

The interaction between lifestyle choices and gene expression goes on every second of every day you’re alive. You are literally rebuilding yourself all the time. That’s the message of hope that the Primal Blueprint offers. Even if you have so-called markers for “defective” genes, that doesn’t mean they will be expressed. Gene interaction is such that environmental factors can potentially allow for someone with BRCA1 and BRCA2 (associated with a very high risk for breast cancer) to never get breast cancer if those and related genes are properly controlled through environment. On the other hand, a woman with no risk factors can still get breast cancer if she directs gene expression towards pro-inflammatory pathways, then down-regulates other parts of her immune system.

As I mentioned last week, most of today’s genome investigation centers on SNPs (single nucleotide polymorphisms) that predispose the possessor to a particular condition (cancer, heart disease, obesity, diabetes, arthritis, etc). I’ve always said that a predisposition is not your final destiny. Even aging itself is highly influenced by gene expression over time. In the course of a lifetime, stem cells divide to repair injury (e.g. inflammation). In doing so, the cells are continually aged. The more the cells have to repair, the faster a person ages. This, of course, is a manifestation of gene expression.

The whole idea behind my Primal Blueprint is this: we know that we can influence gene expression, but – more than that – we know HOW to influence it in a direction of health, fitness, productivity, happiness, etc. The “blueprint” is not the DNA but a set of lifestyle and behavioral guidelines that, if followed, allows you to recast yourself as a healthy, fit person using “controlled gene expression”. The “primal” part comes from the recognition that our basic human DNA is relatively unchanged from the past 10,000 years. As long as we understand what it took to evolve to that point, we can find ways to continue to influence gene expression that are in alignment with that pre-agricultural DNA.

Thanks again for your comments and questions, and please keep them coming.

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About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.

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15 thoughts on “Dear Mark: Gene Expression”

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  1. Actually, we are understanding that it is even more complex. Lifestyle choices such as nutrition, smoking toxins etc. of the mother can effect the kids gene expression patterns. Do a search on epigenetics and methylation if you are interested. But basically, DNA methylation (a natural chemical modification of the DNA) is regulated by environment and here is the neat part it can be passed on to the next generation. So the pattern of inheritance is not just the A’s T’s G’s and C’s of the DNA but also the additional decorations on those bases.

  2. To that effect, recent studies show that mothers who eat lots of carbs and then become insulin resistant cause their developing fetuses to be insulin resistant, giving the offspring a disadvantage from birth. The good news is that this disadvantage can be overcome with appropriate dietary changes.

  3. Mark,
    Thank you once again for clearly explaining the basics of some very complicated stuff.

    This takes personal responsibility and responsbility towards your children to a whole new level.


  4. I agree that genes don’t forge destiny. There’s also a lot of regulation that goes on outside of gene expression, in how proteins interact with one another and affect signaling pathways. Basically, it’s really complicated and no one understands it all. But our ancestors seemed to be getting it right despite having our genes so they’re a good example for us.

  5. It is amazing that we are beginning to understand WHY things we have always thought were healthy (exercise, eating healthy, good sleep etc.) work. And not only that but what TYPE of exercise, diet etc. work at the cellular and genetic level to steer gene expression in the direction desired. The Primal Blueprint is the health philosophy of the 21st century. I can’t wait to learn more. Thanks, Mark.

  6. That makes so much sense, I’m tired of hearing my friends blame their ailments on “bad genes.” Because I’m a bit a naturalist, I’ll use the garden metaphor. It’s not the seeds you’re given, it’s how you nurture them.

  7. As more research is done and as this information becomes available I’d be interested to hear more about what one can do to achieve a desired physical effect. Or is all this going to do is tell us what we already know? Eat well, sleep well, stay active etc. It would be cool to find previously unknown body hacks. Though, I suppose some of the stuff MDA has already published is sort of body hack material… e.g. natural production of HGH, chronic cardio troubles etc.

  8. “The “primal” part comes from the recognition that our basic human DNA is relatively unchanged from the past 10,000 years.”

    Which is where your Primal arguments fall to shambles since this simply isn’t true. Genetically we have little in common with late Paleo people, let alone earlier ones. Evolution is known to occur much faster than you give it credit for and we are not stuck in the mold as you imply. Genetic expression adds even greater options for diversity, which you rightly bring up. But you should focus on a Modern Blueprint instead of the fantasy stuff.

  9. Tina,Tim,

    That’s the same erroneous assumption we discussed last month. Humans may be exhibiting a widening range of SNPs and slight gene variances, but that does not mean that we are evolving at a faster rate. It just means that mutations and changes are not selected out and that normal “drift” happens at a greater rate due to sheer numbers. In fact, since there is no longer any effective selection pressure on our species (no predators, no real threat of starvation forcing us to adapt anew) and a nearly unlimited ability to reproduce, we have ceased to evolve in the truest Darwinian sense. The only two possible traits that appear to have been somewhat selected for in the past 10,000 years are a continued lactose tolerance among some herders (which isn’t even really an adaptation when you realize that we are all lactose tolerant through much of childhood – and when you also look at other possible factors like the effect of WGA on gut turnover) and a possible increase in salivary amylase production I hear mentioned occasionally (pretty weak). That’s it. Everything else on us is supposed to work exactly as it evolved through the first 60,000,000 years – of which 2 1/2 million was “human” evolution, and up until 10,000 years ago, after which time there was no more selection pressure…just bad food choices, too-close living conditions, industrialization and the Internet.

    That’s why the Modern Blueprint so closely emulates the Primal Blueprint. Give me one example of a Modern lifestyle behavior or food that would differ (in principle) from a Primal behavior.

  10. Read ‘Biology of Belief’ by Bruce Lipton PhD and ‘Molecules of Emotion’ by Candice Pert PhD

  11. Mark, have you heard of the nutrutional supplement Protandim? The formulation was develped by the scientist that discovered SOD 40 something-years ago, Dr. Joe McCord.

    ABC PrimeTime did an investigative report on it.

    I’d love your thoughts on whether or not it fits with your Primal Blueprint concept of gene expression.

    You can also go to and type in Protandim to see the peer reviewed studies that have been released since the ABC investigation.

    1. Mark, I would love to hear your take on the Protandim studies as well. I have a family member getting into that product, and I would love to know what is real vs what is hype.

  12. Also interested in your take on Protandim Mark, specifically whether or not the idea of too many antioxidants is toxic, which they claim to solve with the senergy of their formula…?

  13. Any responses or thoughts on Protandim? I haven’t seen any, but new to the site, so I apologize if they are posted somewhere.