Thursday, January 30, 2014

The Human's guide to being Human: How your cells work

Light energy from the Sun interacts with chlorophyll pigments found in plants to convert light energy in to usable chemical energy to power the plants' activities.  In humans, excess energy from food that is not used for daily energy needs is converted in to fat and stored for later use.  Approximately 85 million years ago, primates diverged from other mammals on the tree of life, eventually giving rise to what would become modern humans.  In 1928, Scottish scientist Alexander Fleming showed that if grown in the proper environment, the fungus Penicillium notatum would secrete a substance with antibiotic properties that he called Penicillin.

While there doesn't appear to be much similarity between the four examples listed in the above paragraph, they are all considered biological functions.  There are countless biological functions that occur within the human body on a daily basis, and when you expand that to include all of the biological functions from all life on the planet since life began, you would think it would be difficult to find something in common with all of them.  The thing is, it's actually not that difficult at all. Every biological function, whether it be from bacteria, insects, fish, birds, humans, or plants; or whether it takes place over the course of milliseconds, minutes, hours, or millions of years; is the product of a gene/environment interaction.  

Gene/environment interactions

There are many examples of how we have used the understanding of gene/environment interactions to better our lives.  In the example of penicillin, you may be surprised to learn that there is a completely logical reason that an antibiotic would be secreted by a fungus given the proper environmental conditions.  While the discovery of penicillin was accidental, the presence of an antibiotic can easily be explained by gene/environment interaction.

When Dr. Fleming picked up a petri dish that contained Staphylococcus aureus and had been contaminated with Penicillium notatum, he noticed that a mold had grown that killed the staphylococcus.  In an epic battle for supremacy, both the Staphylococcus aureus and Penicillium notatum were fighting for the limited food resources found in the petri dish.  However, when Penicillium notatum growth is limited by stress(In this case, competing for resources with another organism), it secretes an antibiotic that increases it's chance of survival and decreases the chance of it's competition's survival.  Using a finishing move contained within it's genome, the Penicillium dispensed of the Staphylococcus, won the battle, and became champion of that petri dish.

An infinite number of biological functions such as this take place every day.  As products of  gene/environment interactions, these functions are dependent on the presence of a gene and an environmental trigger that causes the gene to be expressed.  In the instance above, if Penicillium notatum didn't have the gene to secrete the antibiotic, or if the stress due to competition was not there, it would have never secreted it and the Staphylococcus would still be there.  Grown against a different foe with a more forgiving genome, or in an environment with ample food and space for both organisms, the staphylococcus may have stood a chance.  This is survival of the fittest, this is how natural selection, and biology as a whole, work.  In order to to understand biological functions and evolution, you first need to understand what genes are.

Genes and epigenetics

Genes, or DNA, are essentially a blueprint for you, a set of instructions contained within the nucleus of every one of your cells.  Your entire set of genes is referred to as your genome, and the vast majority of your genome is located within the nucleus of your cells and protected by a membrane.  A small portion of your genome is located within the mitochondria, or power plants of the cell, but those genes only code for parts found within the mitochondria.  Genes are often referred to as coding DNA because they are responsible for making proteins, and the part of your genome that consists of coding DNA is fixed from birth and identical in every cell of your body.  A perfect example of coding DNA in Penicillium notatum is the gene that makes pencillin, an antibiotic protein.  Another one found in humans is the gene that codes for insulin, a protein that helps the body store sugar.  The more complex the organism, the more complex the genome...or so we thought.

You may have heard that humans and chimpanzees are 98% similar from a genetic standpoint.  While it is true that our coding DNA is approximately 98% the same, the coding DNA is not the entire story.  Even a banana tree shares approximately 50% of it's coding DNA with humans.  This is because most living organisms are made up of the same types of cells with the same basic machinery in the form of organelles.

Organelles are the cell equivalent of organs, hence the name.  Interestingly enough, an organs' cells contain organelles that perform the function of that organ.  For example, the liver is a detox organ and the cells within the liver contain organelles that make detoxification enzymes, among other things.  These organelles are made in these cells because the DNA contains the instructions to make them and the environment the cell is in tells the cell to make these organelles.  This is how cells know what to do and why skin cells aren't actively making things like insulin, that set of instructions is read in the cells of the pancreas.  The environment communicates to the cell what to become, and the genes put that order in to action.

Taken a step further, your cells become what they become because the environment tells them what to become.  Many people don't realize that the blueprint in every one of your cells is identical.  So how does a skin cell become a skin cell and a liver cell become a liver cell if the instructions are the same?  In his book The Biology of Belief, Dr. Bruce Lipton discusses his work in cellular biology 50 years ago.  When he would take stem cells and put them in a petri dish under certain environmental conditions, they would become muscle cells.  The same stem cells placed in a different petri dish with different environmental conditions would become bone cells.  He explains that the environment interacts with the membrane of the cell and causes certain parts of the DNA to be read, or expressed, and other parts to be ignored.  This is called epigenetics and it is an aspect of genetics that was mostly ignored until recently.

Maybe that junk isn't actually junk

When scientists undertook the Human Genome Project, they expected to find at least 100,000 genes in humans given what they had found in other creatures.  Simple creatures such as C. elegans, a worm, has 20,000 coding genes, certainly a far more complex creature like humans will have more, right?  Not so much.  When the Human Genome Project was completed, it determined that humans had a total of between 20,000-30,000 genes.  What makes this even more shocking is that rice contains between 35,000-56,000 genes.  The problem isn't that we have so few genes, it's that a portion of the genome called "Junk DNA" that we disregarded happens to have a much larger effect on our complexity than the coding genes do.  In other words, what we called junk wasn't junk at all.

Since the "Junk DNA" didn't code for actual proteins, it sort of got thrown out with the trash, so to speak.  It certainly doesn't make sense that it's worthless considering it makes up about 98% of the genome.  However, since it didn't make anything quantifiable, researchers figured it was of minimal significance.  This portion of the genome is something we now call the epigenome, and it's significance is anything but minimal.  While the epigenome doesn't really make anything, it's significance is huge because it tells the coding genes what to do.  While the coding genes make insulin or organelles, the epigenome identifies the environmental condition and activates or suppresses all of the genes that are affected by that particular environmental condition.  If you look at the coding genes as the blueprint, the epigenome is the general contractor that reads the blueprint and puts it in to action. 

The epigenetics of animal development

From the day you are conceived, cells divide and replicate, passing along the genes that are contained within.  As you develop in to an embryo and beyond, HOX genes help guide your development by making HOX proteins that either repress or activate other genes.  In this way, the HOX proteins are a set of orders given out by the HOX genes that say, "Put the thorax here, put the eyes there, put ears here" and so on.  Embryonic development is a great example of epigenetics at play.  You may be surprised to learn that at one point you had a tail.  While you were but a wee embryo in your Mother's womb, you had a tail that eventually disappeared.  It disappeared because you are a human in a human uterus and human's don't have tails.  At some point during the developmental process, an environmental cue came that initiated apoptosis, or cell death, that lead to the removal of the tail.  The same thing happens with the spaces between your fingers and toes, the epigenome received a signal and the cells that made up the webbing between the hands and toes committed apoptosis and you were left with separate fingers and toes. In people with webbed hands or feet, or those born with a tail, the presence of these structures is an example of the epigenome not activating the proper sequence at the proper time. 

The power of the HOX genes also gives us an idea as to how all life on the planet is forever linked.  You may have noticed that all animals have a similar body plan.  While some may have wings, some paws, and others arms, the basic body plan is the same.  In the picture below, you can see how 2 seemingly uncommon creatures such as a fruit fly and a mouse share a similar blueprint for a similar overall body plan.

As you can see, there are similar structures and a similar basic body plan between a fruit fly and a mouse.  This is why we don't see animals that have 3 heads or an odd number of legs unless they are genetic defects.  There are only a few body plans that we see and all are similar because many of the instructions are similar because we share quite a few coding genes.  What makes this even more interesting, and the primary reason I used a fruit fly and a mouse, is that in 1994, research was done where the gene from a mouse that codes for the eye was placed in a fruit fly.  The result...the fruit fly grew a normal fruit fly eye.  This is because the genes are the same, it's not a difference in the specific gene, it's a difference in how and when the gene is activated that determines what type of eye is made, and that determination is made by the environment the cells are in.

Epigenetics and adaptation

So what does all of this have to do with being human and how we work?  Embryonic development is a great example of how epigenetics works, but epigenetics reaches well beyond embryonic development.  All biological functions are products of gene/environment interactions.   Your cells are attempting to put you in a position that is most advantageous to the environment you are in given what they can do, and when the environment remains consistent over time, patterns of gene expression are remembered and passed on to future cells.  Over time, your cells begin to "memorize" the environment by using epigenetic tags that get passed on to daughter cells, giving them a leg up.  When the environment changes for a significant amount of time, these tags are removed and different tags are laid down provided the environment remains constant for a time.

In much the same way, your genome has been shaped to make you better at things that your ancestors were good at.  While the epigenome can change in an individual, the coding genes do not, they are simply shaped in a population over the course of many generations as genes that put certain individuals at an advantage over others get passed on when people with those genes reproduce and have more children than those without the gene.  In addition, genes that put people at a disadvantage and also impact their ability to reproduce decrease or become removed from the population.  So in an individual, coding genes do not change they change in a population over long periods of time.

For example, the environment our ancestors were adapted to was low in food so being able to store fat efficiently is a beneficial trait to have.  Humans who were successful at passing on their genes to offspring were more likely to do this well so we are more likely to see people with genes that are efficient at storing fat.  In the same way, craving sugar and acting on that craving is something that is also advantageous when food can come and go in the blink of an eye, which is why most of us tend to crave fat, sugar, and carbohydrates.  

For most of our existence, food hasn't been that easy to come by.  Being able to store more energy for later use is in the best interest of humans because for most of our existence we have also needed to expend large amounts of energy to procure food.  Now, not so much.  When an organism's genes become adept at operating in a certain type of environment and that environment changes quickly, bad things can happen if there is a mismatch between what their genes are good at and what the environment requires for survival.  Since your genes are passed down to you by your parents, and theirs from their parents, your genes are well suited to an environment similar to theirs as well as their predecessors.  If your genes don't work well with the environment they are in because that environment changes on a dime, a mismatch occurs.  This mismatch between what our genes are good at and the environment they are currently in is likely the impetus for most of the chronic diseases we see today.

All is not lost, however.  The epigenome does allow us some flexibility to adapt to different environments, but there needs to be a willingness to do so in the face of such a drive to eat and be efficient with the amount of energy we use to get food.  In other words, personal responsibility is likely the first step until your body, and cells, adjust to the new environment.  Changing the environment you experience through diet and physical activity should begin to improve your health since it is the environment your genome was optimized for.  If your blueprint, or DNA, is fixed, why would things start to go bad if they've run smoothly for 50 or 60 years?  The likely answer lies with epigenetics.

Your genes are not your destiny

When people do genetic tests to find out if they have the gene or genes that are associated with a disease, what they are finding out is whether or not there is the possibility that a disease is in their future.  They are not finding out with 100% certainty that they will get a disease, that is dependent on if and/or when the gene(s) are expressed, and for how long.  There are people with genes associated with any number of diseases that may never get them.  Identical twins, while they contain the exact same DNA, often die of different causes.  That is because from the time they are born until the time they are married with children and have a career, their environments diverge from one another.  There are even identical twins where one is obese and the other is lean.  This is because the same blueprint has been put under different environmental conditions that have led to different patterns of gene expression.  The result...two different outcomes based on how genes are turned on and off by the lifestyle decisions each has made.

So why does the same plan lead to different outcomes based on specific aspects of the environment?  Why do biological functions occur?  And why may epigenetics help solve some of life's greatest questions?  The answers to these questions can be found by looking at evolution, but first we have to take a look at one more aspect of our genome that we didn't cover.  In the next blog we will go over the zoo of bacteria in your gut often referred to as your microbiome.

Next: Your microbiome