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(Epi)Genetics – and what Jurassic Park got wrong about the ‘Blueprint for Building a Living Thing’

(Epi)Genetics – and what Jurassic Park got wrong about the ‘Blueprint for Building a Living Thing’




(Epi)Genetics

What Jurassic Park Got Wrong about the 'BluePrint of a Living Thing'

Mr. DNA Introduces Genomics . . .

In the summer of 1993, Steven Spielberg’s classic hit Jurassic Park came to life across the big screen.  With it came a novel connection to science and scientific inquiry for millions across many walks of life, children and adult alike.  By the time I was permitted to see it by my parents, the film had already generated a multi-million dollar sequel with talks of a third underway.

Dinosaurs were brought to living breathing reality in a whole new way, that captured the hearts and minds of millions.  Alongside Tyrannosaurus rex and Velociraptors, came a 90-second animated strand of DNA introducing the science of genomics to the world, and the rest was history.  

 

“Genomics:  molecular biology of the structure, function, and mapping of an organism’s ENTIRE genome.”

 

Scientists James Watson and Franklin Crick, having stolen the work of Rosalind Franklin, introduced the DNA double helix in 1953.  By the 1980’s DNA testing was appearing in police procedural dramas and daytime television.  And in 1990, three years before Jurassic Park, the Human Genome Project launched.  

But for most people, the implications of mapping the human genome were hardly a topic for discussion over morning coffee.

So when an animated strand of DNA offered the simple explanation of DNA as ‘A blueprint for building a living thing’ it was immediately understandable and resonated with millions of people in one of the most efficient examples of Science Communication known to history – and we have been fighting that legacy tooth and nail ever since.

In the complex history and science of Genomics DNA is only the start …  

 

For most people, the implications of mapping the human genome were hardly a topic for discussion over morning coffee.

 

So when an animated strand of DNA offered the simple explanation of DNA as ‘A blueprint for building a living thing’ it was immediately understandable and resonated with millions of people in one of the most efficient examples of Science Communication known to history – and we have been fighting that legacy tooth and nail ever since.  

 

“A DNA strand (like me) 

is a blueprint for building 

a living thing-”

 

DNA is complex in a way that a 90-second cameo could never hope to convey. What Mr. DNA did illustrate was how massive an undertaking of genomics truly is. 

 

Unraveling DNA molecules, decoding sequences, and matching up billions of individual nucleotides into recognizable patterns. It makes sense that advances in DNA coincide with the development of computers sophisticated enough to process the vast amounts of data required.  

 

But DNA is not the end product of a genetic process.  Rather, it is just the beginning.

 

Your DNA is a template from which smaller molecules (mRNA) are generated like tiny chemical text messages.  Other parts of the cell (ribosomes) use these messages for building proteins.  Your body, in turn, uses these proteins for everything else.  Specific sections of DNA, known as genes, code for specific proteins or groups or proteins that serve a particular job or task.

 

Proteins serve as hormones, neurotransmitters, both chemical signals and receptors. They create the muscles and tissue that make up 20% of the human body, they make up our hair and nails, our hearts, our guts and even out winds.  Our DNA is responsible for designing every single protein our cells produce, but not all DNA will create proteins.

 

Mr. DNA brought genomics to the world, but at a cost 

                   … he got it wrong.

 

The BluePrint Fallacy . . .

 

The term ‘Junk DNA’ was used to describe DNA that is not being used by the cell.  It is also a term that deeply confused me when I first learned to think of DNA as a Blueprint.  These sections do not unravel to share their genetic information, they do not produce mRNA, and they do no result in the creation of proteins.   

 

A blueprint is a set of instructions, guidelines and measurements for the construction of a building or, in this case, an organism.  But in a blueprint every detail, every note, every single peice of information is used. If I were to ignore entire sections of a blueprint, then the resulting structure might be missing a wall, or the roof, or it may crumble all together.  

 

Blueprints also code for very specific construction.  A blueprint will only ever make the one building it is designed for.  You cannot use the same blueprint for houses, hospitals and shopping malls.  You would need seperate blueprints for that.  

 

Your heart cells, brain cells and muscle cells are all working off the EXACT same genetic code.  The exact same ‘blue print’. And yet each one of these cell types is drastically different from the other.

 

Blueprints also fail to account for recessive genes, where a trait is written in the genetic code but not expressed.  Or how some traits can seemingly skip between the generations.

The process of DNA -> RNA -> Protein is the Central Dogma of molecular biology.

To be fair to Mr. Spielberg, the Human Genome project had launched only three years prior to the release of Jurassic Park.  The project would not be completed until 2003, thirteen years after it launched and exactly ten years after Jurassic Park first premiered. Mr. DNA brought genomics to the world but the explanation he provided was incomplete.

 

The Blueprint model fails to account for;

    •   Cellular Types
    •    Junk DNA
    •    Recessive Traits
    •    Skipped Generations

 

The solution, as it happens, lies not in the fields of either Genetics or Genomics … 

… rather, it lies in Epigenetics.

The Genetic Cook Book . . .

DNA is not a Blueprint – it is a Cook Book.

In any given cook book you will find hundreds of recipes, some relatively simple and some incredibly complex, some pair well together and others do not. Some you will make a thousand times over, while others you may never use.

Each and every single one of your cells, whether it be heart, skin, brain or lung, carries the same exact set of genetic instructions. And yet these cells are vastly different from one another.

 “Epigenetics – the study of changes in organisms caused by modification of gene expression

rather than alteration of the genetic code itself.”  

Your cells are using the same cook book, but they are creating different recipes from within that book depending on their cell type and what they need.  For example;

    • Heart cells produce the protein fibronectin, which promotes healthy cardiac function. 
    • Brain cells produce neurotransmitters. 
    • Skin cells, as every teenager knows, secrete oil, some cells more than others. 

Even down to the proteins that make up the cells themselves. Cells use different recipes from the same shared genetic cookbook, the same genome. But how do our cells decide which protein recipes to use and which to ignore?

 

One way is histone modification, which changes how the DNA coils into tight bundles.  We can think of this as two pages in the genetic cookbook sticking together, making it difficult to read the recipes. 

 

The other way is very similar to how we might use notes in the margins to mark recipes of interest in our own cookbooks.  In your cells, however, these notes indicate which recipes NOT to make, and rather than pencil, they are composed of a small molecule consisting of one carbon atom and three hydrogen atoms called methyl.  Methyl molecules attach to the backbone of DNA, blocking the creation of RNA.  These patterns of methyl molecules (methylation patterns) block out the ‘JUNK’ DNA for that cell, leaving the rest.

 

Just like with pencil marks in the margins of a cookbook, methylation patterns on DNA can change and be changed.

Before you panic, your liver cells are not likely to forget they are liver and suddenly become your heart cells.  Some things are harder to erase than others.  However, a liver cell, for example, might erase the pencil marks (methyl) stopping replication.  That cell may then grow and reproduce uncontrollably creating a large mass within your liver – otherwise known as a Tumor.  Likewise, just as changes in methylation patterns could result in cancer formation, methylation can turn cancer genes OFF.

 

Say for example that you have recently learned you are a carrier of the BRACA gene, a known cause for breast cancer..  You do not have cancer right now, the gene is inactive, but there is a very high likely hood that you will in the future.  

Some patients, faced with this information, may end up choosing a radical double mastectomy, or surgical removal of all breast tissue, rather than risk not only an eventual cancer diagnosis but years of uncertainty with this looming over them.

 

Now instead imagine a future in which, having been diagnosed with this gene, or one day even with active cancer, a patient is able to completely bypass invasive surgeries, extensive chemotherapy, and radiation treatments.  Instead, imagine simply being able to take a small pill.  Perhaps just once or maybe twice a day for a week, and simply turning the responsible cancer gene OFF.  

 

Epigenetic changes may contribute to a significant portion of cancer cases, but cancer is not the only possible outcome.  Changes in methylation patterns of cells shift over time, with exposure to certain stimuli, chemicals, diseases, even COVID.

 

“Epigenetic rewiring of pathways related to odour perception in immune cells exposed to SARS-CoV-2 in vivo and in vitro”

 

One study recently found that the prolonged lack of smell and taste common in long covid patients showed a strong link to changes in methylation patterns.  The patterns of methyl molecules in their DNA have been changed by exposure to the virus, limiting their sense of taste and smell.

  

We see similar things in research all the time. There are recorded changes in the lung cells of smokers and tuberculosis patients. Going back to the liver, we see similar patterns in chronic alcoholics.

 

Methylation patterns change over time and in response to environment exposures like chemicals and disease, but also diet and exercise. Perhaps more importantly, these patterns can also change back.

As we get better at understanding the science behind epigenetic changes, we also get closer to being able to manipulate them.  Drug trials for epigenetic modifiers have been ongoing since the 1940s, with clinical availability in cancer research, Huntington’s, Parkinson’s, and more.

 

Our understanding of Genomics has evolved from the days of Mr. DNA.  We know now that we are not operating off a blueprint, but a vast and ever-changing cookbook, one full of post-it notes and stuck-together pages and pencil scribbles.  And as we get closer to understanding the procedures and recipes more fully, we get closer to closing the page on cancer, perhaps forever.

Key Terms

 

DNA  – Deoxyribonucleic Acids, the double helix of genetic information stored in all cells.

RNA – Ribonucleic Acids, the single stranded molecules made from DNA in all cells.

Genetics – the scientific study of genes and heredity, of how certain qualities or traits are passed from parents to offspring as a result of changes in DNA sequence

Genomics – Genomics is the study of all of a person’s genes (the genome), including interactions of those genes with each other and with the person’s environment

Epigenetics –  the study of how your behaviors and environment can cause changes that affect the way your genes work.

Genes – Segments of DNA instructions for building one or more proteins that help the bodywork

Chromosome / Chromatin – tightly bundled coils of DNA that form during cell division, DNA ‘pack’

Methyl/Methylation – CH3 molecules attached to DNA which inhibit gene transcription

Nucleotide – The chemical ‘Letters’ that make up DNA; Adenine, Guanine, Cytosine, Thymine

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