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24 Apr

Gene Expression: Location, Location, Location

gene1Geneticists at North Carolina State University have revealed an interesting lesson in gene expression: where you live can have significant impact on how your genes are expressed.

The scientists focused on a sample of 46 Moroccan Amazighs, a relatively homogenous group genetically-speaking. The subjects included desert nomads, mountain agrarians and coastal urban residents. The researchers analyzed the white blood cells of the group “to study the impact of the transition from traditional to urbanized lifestyles on the human immune system.” The results surprised even the scientists themselves: gene expression in the group varied by up to one-third based on geographic location and corresponding lifestyle.

They used the latest tools for characterizing the sequence and expression of all 23,000 human genes to compare the three Moroccan Amazigh groups. These groups were chosen because they have a similar genetic makeup but lead distinct ways of life and occupy different geographic domains. Thus, differences in gene expression profiles between the three groups would likely be due to environmental and not genetic factors. The team uncovered specific genes and pathways that are affected by lifestyle and geography. For example, they found respiratory genes were upregulated, or turned on, more frequently in the urban population than in the nomadic or agrarian populations.

via Science Daily

To confirm that differences were environmentally related, the scientists reviewed the genetic profile of random subjects in the three groups and found very little genetic variance. As they had expected, the significant difference in gene expression was initiated by environmental factors.

The differences they found in genetic expression logically fit with the environments’ corresponding challenges. The urban dwellers dealt with the city’s manufacturing-associated air pollution and higher level of viral pathogens on a daily basis. The upregulation observed in their respiratory genes, the scientists submit, is a response to the compromises present in their urban environment. And pollution was only one piece of the environmental picture and the impact of modern urban living. According to the scientists, the striking differences in gene expression were the likely result of a “combination” of lifestyle factors, including “nutrition, history of immune exposure, and psychological stress.”

gene2

This study, along with other research that examines the impact of environment on gene expression, affirms the message we try to offer on a regular basis: we are not at the mercy of our genes. How we play our genetic hand can matter as much as the cards we hold. Where we live, what we eat, what we’re exposed to and how we’re medically cared for, how active we are, and what levels of stress we deal with influence the expression of our genes. In keeping with this principle, the scientists who conducted the study offer this recommendation for future medical research and care:

Insight gained from this study highlights the impact transitions from traditional to modern lifestyles likely have on human disease susceptibility and further warrant the need to incorporate gene expression profiling alongside genetic association studies for the prediction of disease susceptibility.

Our modern lifestyles, as we say in the Primal Blueprint, create a deep chasm between our genetic expression and that of our ancestors. This study of populations in Morocco gives us a hint of that gap. It’s no coincidence that the Blueprint incorporates diet and physical activity similar to that of our primal history. (With good old Grok as our distinguished guide.) Likewise, the Primal Blueprint includes understanding and mitigating the damage created by the compromises of modern circumstance. Our bodies are remarkably adaptable, and genetic expression is evidence of this. However, this adaptability, constantly challenged and finally overstrained, cannot by itself compensate for the many modern burdens we impose. Our day to day choices matter, and knowledge is key.

Thoughts? Check back for more along the lines of lifestyle choices and gene expression in the future.

gabyigl, freckle m Flickr Photos (CC)

Further Reading:

More Primal Blueprint talk

Primal Blueprint Success Story

Nature Tops Nurture? Scientists Wrong Again…

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You want comments? We got comments:

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  1. So, if I get this straight, it means the genes aren’t any different, it’s just the environment causes different expression of those genes? So a traditional family’s child would have the same chance of expressing the immune system characteristics of an urban family’s child if the kids were switched? Makes sense. Though I don’t see that this as conclusive evidence that environment effects genetically inherited diseases, it simply proves that environment effects gene expression in relation to adapting to a specific environment.

    McFly wrote on April 25th, 2008
  2. McFly,

    The power we have over how our genes express themselves is nothing short of incredible. AS for genetically inherited diseases, of course there are some that simply can not be mitigated by environment. In most cases those individuals would have been “selected out” of the population years ago. In others, such as Phenylketonuria, as long as you avoid the amino acid phenylalanine you are fine – eat very much and you are dead, so that’s an environmental adjustment to an inherited disease that can make or break you. However, most of todays genome investigation centers on SNPs (single nucleotide polymorphisms) that predispose the possessor to a particular condition (cancer, heart disease, obesity, diabetes, arthritis, etc). What I have always stated is that these predispositions are not death sentences, but simple red flags that as long as you eat right, exercise appropriately and maybe take a certain supplement here or there, you will NOT develop the condition that the geneticists say you are predisposed to. It’s all about you controlling how your “normal human genes” express themselves. And by the way, no one has a “perfect” set of human genes (or put another way, we ALL have a perfect set of human genes, it’s just that there are countless minor variations that, as long as we take care of ourselves, will have no negative impact on our health. That’s pure personal power as I see it.

    Mark Sisson wrote on April 25th, 2008
  3. It might be useful to augment this post with some concrete examples of gene expression. For instance, something like insulin resistance versus insulin sensitivity would, as I understand it, be a result of gene expression. Given a normal genetic endowment for metabolism, one may become insulin resistant or insulin sensitive based on environmental factors such as diet and exercise. The same for body composition, skin tone, cardio-vascular capacity, strength, immunity, and on and on. We aren’t slaves to our genes. Our genetic endowment permits of various outcomes that we can influence through the choices we make. That’s what I take away from the concept of gene expression.

    Ed wrote on April 25th, 2008
  4. Ed,

    You got it. Evrything we do affects gene expression every second of every day. The only real differences among us are simply the ranges or degrees of possible gene expression for any one particular gene locus or set of related loci. That means that a 5’10″ person with “perfect mesomorphic tendencies” can still range in weight from 110 to 500 pounds depending on environmental influences on gene expression…or an ectomorph from 85 to 275 pounds, etc. Not all women with BRCA1 or BRCA2 get breast cancer even though their risk is far greater, etc etc.

    Mark Sisson wrote on April 25th, 2008
  5. Mark,
    I chose this post as the winner of this week’s Redscrubs Weekly Wrap-up by redscrubs.com. You get two things with this dubious honor: Recognition and hopefully some additional traffic from other medical blog readers who might not ordinarily visit your site, and a free pair of red scrubs.

    Yes, they’re free and yes they are red!:) There is no catch. I am not trying to sell you anything…I promise. This is simply our way of recognizing and giving some sort of award to those who take the time to get involved in the medical blogging community. So, if you’d like your free scrubs, just send me your size and mailing info. by this coming Wednesday. Otherwise, the scrubs go to the first runner up on the honorable mention list.

    Congrats,
    Dr. Incognito

    Dr. Incognito wrote on April 25th, 2008
  6. Thanks, Doc. I’ll stop by to get my scrubs! We appreciate the nod.

    Mark Sisson wrote on April 25th, 2008
  7. What is most interesting is the possibility that the same genes and proteins that cause disease states like insulin resistance are also the same genes and proteins that are upregulated following exercise.

    A protein by the name of JNK comes to mind. With aging and insulin resistance, JNK is elevated and basically functions to shut off the insulin receptor –thus causing insulin resistance. Following exercise, insulin resistant populations show reduced JNK activation.

    The same protein in healthy young adults has increased activated after exercise, and greatly improved insulin sensitivity.

    Interestingly, if you compare older/insulin resistant JNK activation to that of younger healthy people, they end up with the same relative level of activation after exercise.

    Its just fascinating to me that the same protein can cause insulin resistance or actually reverse it depending on the population of interest.

    thescientistofhealth wrote on April 26th, 2008
  8. This is the essence of my “Primal Blueprint”. All we really have to do to be healthy, fit, energetic, happy, productive, etc…is find those behaviors that promote gene expression (or turn it off in some cases) in the direction of health versus sickness. In most cases, this means emulating what our ancestors did prior to agriculture. It’s really a simple list of rules, but it’s very difficult for some people to grasp or to follow within the context of this complex, industrialized, information-glutted, hedonistic, instant gratification society.

    Mark Sisson wrote on April 26th, 2008
  9. Your blog is so informative keep up the good work!!!!

    Carl wrote on March 29th, 2009
  10. I NEED UDPDATE INFORMATION ON EVERY RESERCH ON GENE

    Alieu OLUYEMI wrote on June 7th, 2010
  11. When I first read your claim that “genes are actually programmable” I thought that you had no idea what you are talking about. After reading this post I realize that what you mean is that the effect that genes have can sometimes be controlled by environmental factors.

    It is obvious when I think about it. If somebody has genetics that leave them vulnerable to lung cancer then if they look after their lungs they are less likely to succomb.

    So the PB is a way of creating a positive environment for a bunch of these genes so that we get more of their positive effects and less of the negative ones.

    Very interesting.

    Mike Ratcliffe wrote on July 9th, 2013

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