Why Genes Don’t Tell All

DNA Structure (Genes)I got to view a wonderful TED 2016 presentation on genes by scientist Riccardo Sabatini last night.

I’m paraphrasing the talk (it was on personalized Genetic Medicine) here slightly because I’m not a geneticist, but it got me thinking about how genes influence fat loss, muscle gain, sport performance and well, general life too, and why it’s important for the average person to have a basic understanding of how it all works.

Mostly so you can’t use the easy way out; ‘I just have bad genetics...’

Please bear with my short story here, since you never know when TED talks will be made available.

DNA and consequently genes are VERY COMPLICATED. I won’t deny that, and what’s to follow is a grossly oversimplified representation of how they work.

Think of the most complicated thing you can think of and then multiple that by a few million…

Most people who colloquially use the term, “you’ve got good genes,” really have no idea how complicated that notion is, so the first portion of the talk was largely explaining this with an enlightening visualization.

Most people’s eyes glaze over when you start talking hard science, understandably, but there are some core concepts here worth understanding for the layman that I’ll quickly summarize at the end of the story if you want to skip to that part.

Craig Venter, was the first man (with a team mind you) to sequence human DNA, research largely concluded by 2000, published in 2001, declared complete in 2003, after more than a decade of research.

As such, we’ve only known the entire mapped human genome for about fifteen years at the time of writing.

Sabatini opens by introducing to the stage this famous genetic researcher, but about five people appear on stage each wheeling library carts loaded with massive white binders or about 175 giant books.

The caveat to the introduction?RNA-codons (Genes)

He’s introducing Venter’s genome printed page by page, letter by letter — some two hundred and sixty five thousand pages from memory and about three billion letters of information (well technically base pairs…)! 

He opens an annotated page and reads a few letters AUG, ACG (I don’t recall exactly what they were), ACG, which he says indicate eye colour.

He opens another annotated book to a specific page, reads a few more letters and states, that if just two letters appeared differently, it would mean Venter has cystic fibrosis.

Basically we see Venter’s entire genetic code (a small piece seen at right), the code of life, as expressed down to what are called nucleotides, basically the smallest components of your DNA.

Your genetic code is basically a giant set of rules encoded within your DNA, that determine RNA, which then determines how amino acids get added to form (synthesize) proteins and thus, cells, or how you, end up being you.

The building blocks of life are expressed using three-letter combinations (called Codons) of the letters A, C, G, U (again seen at right – giving the potential of sixty-four combinations per codon), which are used to describe said nucleotides.

Each codon usually corresponds with a single amino acid — which as I outline in this article make up proteins — and combinations make up genes in varying sizes.

Some twenty to twenty five thousand distinct genes within your DNA.

Consider it basically the biology world’s largest puzzle, again with about three billion different possible combinations of these letters in varying sequences.

Like I said, it’s complicated.

According to Sabatini (again from memory) about five million of these letters are what separate you from your sister, your brother, or me.

Less than 2% difference, meaning we’re far more alike than we are different.

A funny consideration, the next time you’re told you’ve got great genes, when really you have mostly the same genes as everyone else, but only a few genes that dictated a desirable quality and it’s realistically only a few letters of code.

Currently out of the three billion, we vaguely understand about what six million of these combinations actually mean. Meaning we only understand about 2% of what your genetic code actually means, and we’re likely still fuzzy on a lot of that.

This is fifteen years after we mapped it out for the first time! As you can see, we still have a very long way to go…

To complicate our understanding of genes further, not only are there so many different possible combinations to test out, but there are also these things called phenotype(s).

Backing up a moment so you understand how your DNA works, RNA actually does most of the work, as your body regenerates every cell roughly every seven years, RNA is what codes each of those cells and determines ultimately how proteins and ultimately cells will behave.

RNA is kind of like a simplified version of DNA that is easier to pass along, and well sometimes how that message gets passed along, certain cells can end up like a very funny version of the game of telephone, as genes get expressed or repressed during the copying procedure (not exactly how it works…).

Basically a phenotype is the result of the expression of your genes due to environmental factors and the interactions between the environment and your genotype (the fundamental code).

Ultimately this leads to some variation from year to year even within the same person.

Your DNA is the like the base code, RNA is like the new simplified version of that base code, and every time RNA signals you to build something new in the body there is the potential for change.

Meaning, your genes actually are constantly changing and your genetic code when you were 15 is different from what it is now.

There is actually an entire field of study that looks just at this component of genetics called, ‘Epigenetics‘ or basically the study of how environment influences phenotypic trait variations, and effectively switch genes on or off like a light in your house.

Still with me?

The next time someone tells you the ‘human genome’ hasn’t changed in 10,000 years, you can now feel smug and tell them they are wrong; That in fact their own genes have changed a fair bit since birth.

It’s actually a lot more complicated than this, but I’m doing my best to explain it as simply as possible, geneticists with a better way to simplify, please leave a comment, I’m happy to have a better way to explain this.

Summary So Far…

This is a very complicated topic, but like I said, some points are really worth understanding for your long-term fitness, nutrition and well-being.

Mostly because knowing the basics of this can help you form a growth oriented mindset and a successful outcome.

  • Your DNA is kind of like your own personal operating system (akin to Linux, Windows or iOS or OS X) that determines fundamentally how things should end up behaving (like any operating system, it doesn’t always end up behaving like it should…yes I get frustrated with Android and iOS all the time…)
  • ‘Genes’ are really small regions of DNA that encodes a specific purpose/function in life (looking at lines of code on a computer for instance that reveals small ‘functions’ that together add up to the capability of the operating system) — you have about 20,000-25,000 genes
  • Nucleotides, are the smallest component of your DNA (combinations make up Genes) and you have about 3 billion in combination (it took more than a decade to map them all)
  • These nucleotides are organized into groups of 3, called codons, which make up singular amino acids that ultimately when combined are your genetic code or genotype. Genes program your body to do certain things like grow to a certain height, or end up with a certain eye colour; With some having more or less influence and being larger or smaller than others
  • One small nucleotide change can lead to some significant differences, with as little as 2 nucleotide differences meaning a person could have a serious medical condition
  • About 5 million nucleotides are what makes us different from one another (less than 2% of the code), meaning you’re more similar to your next door neighbour than you think
  • We know roughly what 6 million of these nucleotide combinations do in life or lead to, at least to about 85% or so certainty (it’s complicated)
  • RNA is like the scribe of DNA, every time you produce a new cell, RNA copies it’s current interpretation of DNA, leading to how amino acids form proteins within the body
  • When copied, your environment can actually dramatically influence what part of the genetic code gets translated in that process (essentially mutated, or a computer bug if you prefer that reference) and how cells behave by flipping on (expression) or off (repression) certain genes based on environmental cues (there is a little more too it like protein folding and such, but that’s the gist…)
  • Your genotype (DNA) dictates how the operating system would like everything to behave, but your environment ultimately heavily influences how it’s translated, in what is essentially the biological version of the children’s game, ‘telephone
  • The environment creates new adaptations within your genotype into what are called ‘phenotypes’ basically new translations of what RNA thinks DNA is trying to say at the time
  • Epigenetics is the study of how certain bits of your genetic code get expressed (or repressed) based on external environmental factors (basically the study of phenotypic trait variations) and ultimately lead to new versions or different interpretations of your base DNA/genetic code

Now that I’ve made myself appear smarter than I am to everyone who isn’t a geneticist, the reason it’s important to understand how genes work, is because they often get painted as an all or nothing scapegoat as to how much control you really have over your body.

Spoiler Alert: You actually have A LOT of control!

What ‘Genes’ All Means

There really is no way around it. I can’t sugar coat that genes do contribute to your current situation.

You will have a very hard time even without excellent skill playing in the NBA if you’re not fairly tall.

You will have a very hard becoming a male model or bodybuilder, without genes that give you good proportions, a good jawline, and good tendon structure in your abdominals.

If you’re a little bit overweight, have trouble gaining more muscle or don’t quite seem to have the lever advantage to compete at a higher level of your sport, genes could be part of the reason.

But are they the only reason? NO! Not even close…

You will never be in the NBA just because you’re tall, and you’ll never be a male model without weight training and closely monitoring what you eat.

Yes there is a basic underlying DNA genetic code for everyone, that can assist you in or deter you in some respects.

Yet for many reasons that code changes regularly throughout life and your genetic code can literally be changed.

When you freak out at age 35 about gaining a few extra pounds, and your ‘good genes’ are no longer working, you’re probably right, but the decline in the performance of those genes has a hell of a lot to do with the environment you’ve lived in since you were 15.

What skills you developed. What foods you ate. How much sleep you got. How much vacation you took. How much stress you managed.

It all influences how genes behave and over time your nucleotides and codons have changed how certain genes function.

For the same reason a child born with blue eyes and blond hair, won’t necessarily survive past age 3 with those same traits.

I now have hazel eyes and dirty blond hair, both my brothers are slightly darker haired and eye colour varies even though more than 98% of our genes are identical. We were all blond hair, blue eyed babies.

Now that you know how genes work, you know that each time your body creates new cells (and it kills/builds about 50,000 new cells each day) there is an opportunity for a new variation and thus a new outcome.

By all accounts, a generalized summary of research (it all depends on what you’re studying) indicates that how your body continues to develop is at least 50% in your control.

More than half!

There are plenty of other confounding complicated observations that completely overshadow the basic notion that genes are your fate.

These makes genes more a probability game relative to environment, than an absolute science. You could be a carrier of a certain gene or gene combination and never pass it on to any of the children you have.

In another instance, IQ might be roughly 70% associated with genes on average in the US. At Harvard though, you might find that 90% of IQ is associated with genes. In impoverished areas of major cities though, the genetic heritability of IQ might be closer to 0%.

Why such a huge variance?

We’re only using statistical probability to provide some reference points, but the reference point in the case of genetics is a constantly moving target as your genes change throughout the course of your life based on your environment.

Genetics as of yet are not studied within an absolute, 100%-of-the-time-this-happens situation, as far as I’m aware.

“Today, few scientists believe that there is a simple “gene for” anything. Almost all inherited features or traits are the products of complex interactions of numerous genes.”

Remember, we only vaguely understand what about 2% of the genetic code means and it isn’t as simple as ‘this gene does this’ it’s usually this gene, and this gene and this gene might lead to this.

And that’s just a loose assumption most scientists make, the influence of genes on everyday life can vary considerably with certain traits like height, though fairly easy to predict via genes, it is certainly influenced over time by adequate nutrition.

If you were stressed as a fetus or grow up malnourished, then you certainly cannot reach your genetic height potential, but outside of making sure you have a decent diet during growth and development, and minimized chronic stressors, there is nothing directly that you can do to influence height.

While you have little control over height, or bone structure or tendon structure, you have considerably more control over your body weight based on your frame.

Is it possible for everyone to walk around with a six-pack? I’m not so sure…as far as I can tell the tendon structure is more largely genetic.

However, there is ZERO reason to doubt so that everyone on the planet shouldn’t be able to reasonably control their body fat levels via behavioral modifications — and in some cases medical modifications to treat something like hypothyroidism for instance — to levels associated with good health.

i.e. Between 14-32% body fat for women, and between 6-25% body fat for men or roughly 20-25 BMI.

Yes there are genetic components to things like leptin secretion (hunger hormones) and other small things associated with body fat retention, that can make that process more difficult or less difficult, because they heavily influence energy storage, dispersement or output.

However, your environment has a HUGE impact on all of that.

My main point is that based on everything we know so far about genes, you’re definitely not doomed being a little heavy your entire life just because you can’t visualize a time in your life where you weren’t a little heavy.

You have a lot more control over how your genes behave than you think!

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The Caveat

There is an emerging field of study called ‘nutritional genomics.’

The study of how your genes interact with your nutrition, and it’s by far the most interesting stuff I’ve stumbled across when it comes to nutrition in the last decade and personalizing nutrition to specific need.

i.e CONTEXT DEPENDENT

What has it shown so far? Not as much as you might hope, there is no real such thing as a ‘blood-type-diet‘ for instance.

We’re probably decades away from using it constructively for nutrition in any meaningful way — and I’d personally argue that even if we understand it, changing human behavior to follow it will still be harder than understanding nutrition and it’s genetic influences.

We’re getting new bits and pieces though, that I can’t possibly summarize here, but I’ll give a few examples.

Certain people have a gene (CYP1A2) that is one of two types.

A fast or a slow version.

People with the slow version break down caffeine slowly and caffeine consumption may increase cardiovascular risk factors.

In people with the fast version, caffeine consumption lowers cardiovascular risk factors and they will break down caffeine quickly in the liver.

There are compounds in broccoli that can switch on a certain gene that leads to a “detoxification” process being run by the body.

You may have a high copy number variation of the gene AMY1, and thus produce more of the enzyme amylase in your mouth.

As a result you probably break down starchy carbohydrates better than people with a lower copy number variation, however again, genes don’t always work like that.

This study shows that although copy number variations of the gene AMY1, do contribute to the production of amylase, there are also several other environmental factors that also contribute:

  • Hydration Status
  • Psychosocial stress level
  • Short-term dietary habits

In big picture thinking, yes, genes contribute in certain situations, but variations due to environment can create just as much of an influence and we still have a ton of research to do in what is basically a very new field of research.

This is all very new and not very well understood, given the billions of combinations to study.

Remember genes are actually a constantly moving target to study, so it’s possible that CYP1A2 or AMy1 can be turned off or on, or that different variations behave differently, or that other nucleopeptides might alter how they behave.

Lots of information to research, so little time…

One day your genes might influence what we tell you to eat or how to exercise, but as of now, your environment seems to be far more important and controllable so I recommend focusing on that.