Genetics – Origins 🧬


29 minute read

Science-fiction has always been fascinating. Growing up watching Sci-fi has ensured that I am always excited about the future. From Smartphones to Smart homes, voice-enabled AI to driverless cars. While not all of Science fiction has come true, at least not yet, we seem to be making progress.

An area of Science fiction that has seen relatively much less action in real life, the superheroes. Is that never going to be possible? So it got me interested to read more about what is currently going on in the world of Genetics.

Genetics is the study of genes. Genes are the software that runs a biological organism. Genetic engineering has indeed made progress over the last 2 decades, we have just not seen superhumans yet. But we are on the path.

Given my fascination with the future, I wanted to understand, what lies ahead. I have been keeping an eye on the developments over the last few years. And suddenly it seems we are very close to a major shift in what we know about Genes and what can we do with them.

Even without following the field of genetics, a lot of you would have heard about CRISPR recently. The latest technology we have to edit genes or the Human Genome Project, where Scientists across the world are trying to understand the genes inside a human.

I started researching more to write a piece on Genetics. But as I researched more, I understood that the story of Genetic Engineering is incomplete without properly understanding genes themselves. Before we can talk about Genetic Engineering, we need to talk about how did we reach here.

The small piece became a larger piece and then an even larger one. This is a 3 part series on Genetic Engineering.

  1. Story of life – Origin of Gene
  2. Genes and Evolution
  3. Genetic engineering

This is the first part of the series.

I also realized there is just a lot of side information I would like to share, so I added this. If you click on the highlighted text, you will get some side information. Try it out.

Emergence

The story of gene editing is the story of who we are and how did we evolve into such complex species in the first place. Complex Genetics that we see all around us, is the result of the continuous increase in the complexity of chemicals.

Emergence is a concept that tries to explain how simple things become smarter when they act together.

Emergence is the story of increasing complexity in the universe. At some point in time, there was literally nothing. But a few billion years later, here we are, mildly intelligent species.

Over the last couple of centuries, we have made progress in understanding what happened in the past. A human lifespan is too short in the context of the Universe, or even life. But over generations, we have got more answers and more clarity on the origins.

The earliest elements worked together to become part of complex compounds. The complex compounds came together to form a human cell. Cells worked together to form more complex biological organisms.

Ladder view of Emergence in Biochemistry

When atom joins together to form a molecule, the properties they display are vastly different from their individual properties. Just adding an atom to a molecule completely changes the properties of the molecule or the form in which they come together. Whenever things come together they exhibit properties that those things individually do not have.

To understand genetics, we need to zoom out and understand what genes are, how they came into existence, and what is their significance to life.

The Big bang

To get the context of most things, you need to go back to the starting point and if you trace back enough everything starts with one event, The Big Bang – the beginning of everything. If you zoom out far enough, every event has been triggered by the first event of the universe.

At the beginning of time, T0, there is total darkness. There is no light, no space. Nothing exists at this point in time. A sand grain is about 2mm. A naked eye can see an object as tiny as 0.1 millimeters. An atom is about 0.1 nanometer. The universe is currently less than a trillionth of the atom at this point.

All of a sudden, it explodes. The universe has begun its expansion. We have a lot of energy expanding outwards. The temperature at the 1st Plank Time is close to 100 million billion trillion °Kelvin. Matter and energy are not that different. They are pretty much the same stuff. The big bang explodes to create matter and anti-matter. And as soon as matter and anti-matter touch each other, they annihilate.

From all of the matter and antimatter created in The Big Bang, almost all of it combines and annihilates. Just a billionth (1/1000000000) of the matter somehow survives. From a size of less than an Atom, the Universe has expanded to a diameter of more than a billion kilometers. From the empty darkness a fraction of a second ago, we have light all around. This light will remain visible billions of years in the future as Cosmic Radiation.

This remaining matter from The Big Bang makes up the Sun, Earth, our bodies, the food we eat, the air we breathe and the stars you see in the night sky.

From a small spec of nothing, the Universe has quickly expanded to billions of kilometer in diameter. The temperature of the Universe is extremely hot. Even subatomic particles can’t survive in the current conditions. decreasing with the increasing dimension and expanded space. The only things that can survive right now are quantum particles, the level at which matter and energy merge. We have gluons and quarks zooming across the universe.

As the 1st second passes, the universe has started to cool. The temperature is still about 10 billion °Kelvin or still extremely hot. By the end of the 1st minute, the temperature has reduced to about 1 billion °Kelvin and it allows the formation of more complex particles. The universe now has subatomic particles: neutrons and protons. Over the next few minutes, Nuclei is formed and suddenly from everything happening in seconds time is going to slow down heavily.

It takes between 300,000 to 700,000 years for the temperature to cool down to about 10000 °K or very hot, instead of extremely hot. This allows for formation of more complex matter. The first Hydrogen and Helium atoms are now the most abundant matter in the universe and will remain so throughout the next few billion years. It will take a few hundred million years for the first galaxies and stars to start forming. While time seems to have frozen, the Universe is rapidly expanding in space.

The formation of newer, more complex forms of matter is the story of how the universe is always working to increase the complexity. Quantum particles create Subatomic particles, which in turn create Atoms ⚛️. And Atoms, in turn, combine to form molecules.

Over the next few billion years, the universe expands at an even faster rate to form larger galaxies 🌌 , stars ✨ , and more empty space. While Helium and Hydrogen have now been around for a while, this phase helps in the creation of Heavier Elements. These elements here are your greatmillion grandparents.

Click for larger image

It will take 9 billion years after The Big Bang for the Solar System, Sun, and Earth to come around. The formation of the solar system, in itself, is a fascinating journey. Our Sun 🌞 is most likely a second-generation star, which was formed from a Supernova explosion. 💥

The explosion throws away all kinds of elements, including the heavy elements that were formed inside the core of the star that exploded. 99.9% of all the matter thrown away is pulled back in the center of our Solar System. This makes up our Sun. Due to extremely high gravitational pull, the core of the sun is under extremely high pressure. The pressure is looking for a release. The fusion of hydrogen and helium inside the core of the Sun begins, lighting up the Sun.

The remaining matter just orbits around the sun for a few thousand years, and slowly starts to come together. Initially, the matter is attracted to each other due to electrostatic forces that pull the tiny atoms towards each other. As smaller matter sticks together to form larger bodies, the gravitational force starts becoming stronger. The collisions between these larger bodies become even more devastating. Once large enough bodies are formed, their gravitational pull will pull all the smaller bodies in their orbits. The largest of these in every orbit will become planets, swallowing all the other smaller bodies in their orbit.

Early Solar System

The dust that is floating around constantly gets heat from the sun. This helps in increasing the complexity to a higher degree. Minerals and heavier elements are formed. The heat and energy from the sun, throw gases towards the outer side of the solar system. The end result, we have small dense rocky planets close to the sun, and large balls of gases towards the outer side of the solar system.

These collisions and the formation of the planets take a few million years. During this process, there is an abundance of energy all around. The energy of the mini planets 🪐 colliding with asteroids ☄️converts massive kinetic energy to heat energy. There is also an abundance of radioactive materials.

The heat from the sun and radioactive materials, all combine to make the Earth like a ball of molten lava. This allows the Earth to go through the process of differentiation- where the heavier elements sink to the bottom to form the core of the Earth and lighter elements float to the surface.

The lighter material like gases of Hydrogen, Helium, Methane, Water Vapor, Nitrogen bubble up to form the early atmosphere of the earth. The silicates float up to the top of the surface and form the crust of the Earth. The hot gases of Methane and others, form Carbon dioxide and trap the heat from the sun to form a red sky. Then over the next few hundred million years, the earth cooled, the water vapor condensed and we had oceans. This Era on Earth is called the Hadean Eon.

Throughout the process from the starting of the formation of our Solar System, the formation of the earth, and multiple asteroid hits, there was a chance formation of Goldilock conditions for life. The conditions for life on earth were just right. This includes the distance of the planet from the sun, the right chemicals at the right temperature to create the first building blocks of life.

Thinking about the Goldilock conditions is necessary to imagine life itself. This has helped scientists to identify other planets where life may exist. There are estimated about 40 billion planets in Milky way that may satisfy the Goldilock conditions. But does this mean that it is easy to create life? Well, it does significantly improve the chances of life being formed when you have billions of other options. But as we will go further, we would realize, life and more specifically intelligent life as we know it has to be able to study genetics 🧬, need much more than just the right distance from the Sun.

Since the creation of the universe matter has organized itself to form more complex compounds. 9 billion years after The Big bang, we have the Earth. The journey that started with gluons and quarks, over billions of years has self-organized for the formation of mineral, heavy metals, and complex chemical compounds. In one way the underlying components of these still remain Atoms, Subatomic particles, and even below the quantum particles. Earth has now existed for more than 500 million years but it is yet to be seeded with life.

Origins of life

Before we discuss the origins of life, we need some boundaries to define what is life? Here I am not referring to life as our thoughts, or in the context of humans. And while yes, you only live once, but so does each of the other species that created this environment. So we will be looking at life, not from a philosophical point of view, but rather strictly from a Biochemistry point of view.

A regime that contains a hereditary program for defining and directing molecular mechanisms that actively extract matter and energy from the environment, with the aid of which, matter and energy are converted into building blocks for its own maintenance, and if possible, reproduction.

Fred Spier, a biochemist, genetic engineer and later a cultural anthropologist

When we discussed the coronavirus, we put the virus on the edge of a living being. The reason, it could not without a host or independently perform all the functions to be categorized as a living-being. We categorize something as living if it had the ability to do the following.

  • Metabolism – the ability of an organism to produce the substances and energy it needs to sustain itself. Catabolism is the break down of materials to provide the building materials, heat, and energy, and anabolism is the build-up of more complex compounds for growth and maintenance of the organism.
  • Homeostasis – the ability of an organism to regulate its internal conditions, such as the chemical composition of its body, so as to maintain health and functioning, regardless of outside conditions
  • Reproduction – the process by which organisms produce offsprings of the same kind. Organisms belonging to the same species can interbreed and produce fertile offsprings.
  • Adaptation – a change in structure, function or behavior by which a species improve its chance of survival in a specific environment. 

When we look at early life, there is a possibility that it did not satisfy all the conditions, just before it did. Formation of life, as with other things like the Solar System, did not happen in an instant but was rather a gradual evolutionary process.

We briefly touched upon the Goldilock conditions that favored earth during the whole process of the creation of life. Some of the fundamental conditions, that Scientists currently believe are the three Goldilocks Conditions, needed to be satisfied for life to emerge:

  • Variety and abundance of chemical elements
  • Energy (not too much and not too little)
  • Water environment. 

Where did life originate?

There is hard fossil-based evidence that life existed on Earth 3.5 billion years ago. But our best estimates today put life existed on earth as far back as 3.8-4.1 billion years ago.

Panspermia is the hypothesis that life exists throughout the Universe, distributed by space dust, meteoroids, asteroids, comets, planetoids. Distribution may have occurred spanning galaxies, and so may not be restricted to the limited scale of solar systems. In this theory, life was not born on earth but was seeded to Earth by an asteroid.

Iso-propyl cyanide, the most complex compound has been detected in a star-forming cloud 27,000 light-years from Earth. The discovery suggests the building blocks of life may be widespread throughout our galaxy. This theory has recently started getting more acceptable, as we realize that life molecules or molecules that are the building blocks of life have been found in space and on asteroids.

When we sent out Voyager, we inevitably sent out life in the form of microbes and bacteria. If the planet, in the end, crashes at a planet with the Goldilock conditions, can that planet be seeded with life? Well, we will not know that in our lifetimes, given that all such planets are many light-years away from Earth. But we have sent life out in the space, and if it can adapt and survive the journey, we may be seeding life to another planet.

But that does not really answer anything about the origin of life, so let’s try to work with theories that put the origin of life on Earth itself.

For the scientists that agree the birth of life happened on earth, the debate is small given the Goldilock conditions for the formation of life. The 2 most prominent theories put the origin of life on the surface of the oceans and on the ocean floor, deep underwater.

The most widely accepted theory today is that life originated near the volcanic vents on the ocean floor.

Volcanic Vents on the ocean floor are rich in biodiversity

Components of life

While there are multiple theories around where life was first created, there is also a large consensus around what it would have taken to create life. Early Earth, had conditions in which life could emerge.

A pool of chemicals in water pushed by external forces would have formed the first organic chemical compounds. Early oceans were a soup of chemicals rich with complex molecules, produced by natural chemical reactions. This soup had chemical reactions happening everywhere and the complexity kept increasing, till eventually, we had living cells.

At this point in time, free Oxygen levels on earth were negligible, and that is a good thing. Oxygen is a highly reactive element and the birth of life, would not have been possible in an oxygen-rich environment. Rather early life on earth gave the oxygen that we all breathe today.

How do we know life is just a different kind of molecular mechanism and not something more profound?

Well as mentioned in the beginning, this view is a biochemical view of life. It does not respond to the philosophical questions around life. While the ancient view of life has always been that life in itself, is different in composition from the non-living. Without proof, it was probably the most valid theory we had around the composition of life.

But now we now know that life is just molecules following a different mechanism. We know it because Scientists over the last few centuries have tested these claims.

A commonly held belief for the majority of human existence has been that matter in life is fundamentally different from the matter in non-living things. Living-beings contain some non-physical element or are governed by different principles. The belief that living-beings existed because of a Vital force or Vital Spark was called Vitalism. The chemical compounds that are found in living things were called Organic Compounds and the ones found in non-living things were called Inorganic compounds. Ancient healing practices had vitalism as a major influence in the medicinal approach. These healing techniques had the belief that disease results from an imbalance in the Vital force.

Urea!!

In 1828, Friedrich Wohler converted Ammonium Cyanate to Diamine Ketone commonly referred to as Urea. This was the first experiment that disproved the belief that organic compounds were special or they could only be gathered from living organisms. Till that day, there was no substantial proof that organic matter or the matter of living things was similar to the matter of non-living things or even that organic matter or compounds could be formed from non-organic compounds. Today organic chemistry is the field that looks at any compounds that contain Carbon.

Origin of Species

When Charles Darwin first wrote the Origin of Species in 1859, it literally sent shockwaves throughout the world. It was as radical as the laws of physics by Newton. It showed how all living-beings evolved from the same species. It changed the nature of work in biochemistry forever, and now scientists knew that at the core of the living-being there is a common component. This further strengthened Cell theory, which had been in discussion for over 2 centuries and had just decades ago been finally started to be accepted. But we will come to evolution later, his views on the birth of life are of interest here.

We could conceive in some warm little pond, with all sort of ammonia, phosphoric salts, light, heat, electricity present that a protein compound was chemically formed ready to undergo still more complex changes. 

Charles Darwin

Alexander Oparin in his book The Origin of Life that was published in 1924 also put forth the theory of gradual progression from simple chemistry to living cells.

Stanley Miller Experiment

Till the 1950s Darwin’s pond, Oparin’s Chemical soup, and other such theories were just speculative. While these theories were founded on a good fundamental understanding of Chemistry and Biology, they also had a relatively wide consensus, but they could not become a scientific hypothesis, as no one had been able to observe or test these hypotheses.

And then came Stanley Miller. In the 1950’s he started work on an experiment along with Harold Urey, his professor. The Miller-Urey experiment was to set up conditions similar to Earth at that time, inside his lab in a controlled environment.

Miller-Urey Experiment
  • Water would model the ancient ocean
  • The heat would boil water to mimic evaporation and form water vapor.
  • To model the atmosphere, they added gases Methane, Hydrogen, and Ammonia which were believed to be in abundance during that time period.
  • A condenser would cool the atmosphere, allowing water molecules to form drops and fall into the ocean as rain.
  • To mimic the forces that existed like lightning, geothermal, they added sparks to the atmosphere.

The goal of this experiment was not to create life but to test the first step in the creation of life. The first step in the Emergence ladder of life, can simple chemistry in the right conditions naturally, give rise to complex molecules of life naturally.

After a couple of days, the water turned pink, and just in a week, it became brownish-black. The result, many complex molecules had been produced. Among these were Amino Acid, which till this time was thought to be produced only inside the bodies of living organisms. That they could naturally occur under such conditions was an amazing discovery.

  1. It clearly simulated biomolecules, can be formed in ancient earth-like conditions.
  2. It moved the idea that life emerged from chemistry, at least in part, from speculation to legitimate testable Science.

Many experiments have since been done with different environmental conditions, different starting chemicals and different sources of energy. Multiple experiments have shown that molecules of life can form in a wide variety of environments. 

These experiments can not really tell us which of the conditions are true, but enough experiments can confirm that life can emerge from chemistry. Biomolecules could emerge from non-living chemicals.

Deep underwater

Robert Hazen then went on to create the conditions of the most commonly held theory, that life began inside a deep underwater oceanic floor around the volcanic vents.

He went on to create a high-pressure, high-temperature environment. He started grinding minerals and rocks to create the surroundings of the environment. He wanted to mimic deep ocean floor conditions. The experiment was a success. The simple atoms and molecules ended up producing organic molecules, and slowly they became stable and lasted longer in their state.

All of the above ended up giving us the field of Chemical evolution. While the exact conditions may not be known, what did become clear was that life could arise from non-living chemicals. It may not be the life we know now, but that is because of the part of Biological Evolution is still missing.

Synthetic Cell

In 2010, Craig Venter successfully created a synthetic cell. Till now we have been discussing the building blocks of living organisms. But almost a decade ago scientists were successful in creating a synthetic cell from scratch. A cell whose DNA had been printed by a computer.

Craig Venter and his team went on to create a synthetic bacteria. They isolated a cell and removed all of its genetic material. Then they used 4 bottles of chemicals, to create a new DNA, and insert it into the membrane. The cell booted to life and has reproduced a billion times.

They were even able to add watermarks inside the genetic code, use a different letter to mark the start and end of code that should be deemed as junk by the Bacteria, but can be read by the scientists. They put in an easter egg inside the code and left a website address. So if you happen to start reading DNA and come across this, you can send them an email saying “Hi, I found the synthetic species you created”.

Since then, Jason Chem and his team have been successful at creating the E.Coli genome from scratch.

We will come back to this experiment when we discuss Genetic Engineering, but let’s head back to the time of early Earth and get a life.

And then there was life…

Early life was closer to complex organic chemical compounds rather than the complex biological beings that we see around us today. Imagine a chemical compound that is always looking for an unstable atom, to become more stable itself. So at this time on Earth, a large variety of chemicals were reacting with different kinds of chemicals. They were forming new bonds, breaking old bonds, pushing out electrons from a chemical, latching on to electrons. Well, it was a mess.

The process of a chemical reaction resulting in a catalyst for the same chemical reaction is called Autocatalytic, and if a set of such chemical reactions form a chain, it is called an autocatalytic set. The chemical reactions that led to the origin of life are similar, that once started the reaction will continue till an external entity breaks the reaction.

Let’s take the example of a burning candle. If you have oxygen and you raise the temperature high enough by using an external source, the candle keeps burning, until oxygen gets over or the candle is over. In this case, the fire is using the candle and the oxygen to keep itself alive.

Just like once you are born, all the chemicals in your body will keep functioning and doing their job, till you die. If some chemicals are unable to keep up their job, due to lack of resources or an external force, the reaction stops and you are dead.

Protein World

So initially complex chemical molecules in the soup of chemical, start reacting with each other trying to break each other apart. But a few complex organic chemicals, Amino Acids or Ami get together. They realize that they can keep going longer if they form a team. If they can form a larger group of Amis, they will be able to defeat all the other simpler chemicals and manage to stay alive. They name their team Protein. There are enough chemicals to go around and each of the individual chemicals has a different goal. But they all have one common goal, to become stable and live longer. So they form a symbiotic relationship and decide to stick together. This gives them the opportunity to fight all the other chemicals and become stronger. As with any team, they need a bond to keep them together. They call this bond between different Amis as the Peptide Bond.

Amis forming teams to become Pros

So Proteins or Pros as they have become, realize that they can use different strategies to achieve their goals. Pros could use different players amongst the Amis, to create different formations like Soccer teams. So you have multiple different teams, coming together in different formations to win against simpler chemicals. They find out, some Amis hate water, while some have no problem being wet all the time. So they make formations in which outer Amis protect the inner Amis from water. This results in the creation of several different Pro Teams or different Proteins. The aim remains the same, survive and live long.

Different Types of Protein Structures

RNA World

On another side, some Nitrogen-based chemical molecules get together to try out a similar strategy. Can they together become more stable than alone? So a bunch of them decide to stick together and take collective action. These were Adenine, Uracil, Cytosine, and Guanine or simply AUCG. They want to have a cool nickname to indicate you are part of this group. They all agree, they will now be called Bases. So A, U, G, and C were happy being part of a team and started calling their cousins to form bigger teams and defeat the other chemicals.

Just like Amis, they needed a bond to keep them together. They figure out, everyone is close to Ribose and Phosphate. They ask Ribose and Phosphate to join their team. Ribose and Phosphate join and form the backbone for this team. So they started creating long chains of Sugar-Phosphate like Twizzlers. This also triggers the affection of sugar within living-beings. So they start assembling long Helix chains of Sugar adding Bases on the top and kept going. This process of organizing all of these separate molecules to come together in an organized structure is called Self-Assembly.

RNS Structure

Ribonucleic Acid or RNA molecules now have to keep fighting off different chemicals to stay alive and keep the team together. Other chemicals are constantly trying to break the team. RNA teams have to experiment every time, trying out different things to fight off chemicals. Even if they are able to defeat their enemies, they are in the same battle next time a cousin of that enemy comes to attack them.

One time while daydreaming, an RNA molecule imagines, it would be fun if once, I have survived something, I can just write down. It does not have to always try out new things to fight off chemicals. If I decide how to kill chemical A, all their cousins can be defeated using the same method. It looks around but can not find a pen and paper. It also could not do much with it, given it has no hands. So RNA tries to look for ways to store information, that it can access later. It realizes it is good at creating helix chains using the Bases. It wonders, Why not create a language for itself to remember and pass instructions to itself at later times? Like morse code or binary language for computers. In the process, it creates the first language, the genetic language. It can now just read an RNA strand to retrieve the information. The letters of the language AUCG.

So it starts organizing small RNA strands into large super-chains that in part start acting like an encyclopedia of its knowledge.

RNA team also realizes that while they were forming the long helix chains using Sugar, some of their teammates or Bases had developed good bonding. They could form their own bonds by holding hands. A liked U, and C liked G. They were more than happy to form a bond between themselves. This gave RNA the power to create more complex structures than just a helix chain.

Now RNA molecules could do both functionalities, they could store information, and then use that information to synthesize organic compounds that help them survive in their surroundings and fight off other chemicals.

RNA Base bonds and folding

Once RNA learned this, it became a very cool molecule capable of doing a lot of things. RNA teams started trying to see what all they could do.

RNA at that point did not know that it would become the essence of life and become the single most important molecule for everything else to come in the future. But the bond of base-pairs would become a problem for RNA, that it had not yet realized.

Abiogenesis

Abiogenesis is the natural process from which life arose from organic chemicals.

Both the stories above talk about the different world hypotheses on the birth of life. We still do not know for certain, if we had the Protein world first, or the RNA world. In both the stories, it is not really one protein or one RNA that is trying to survive. Millions of such complex compounds came into being, RNA strands would break as soon as they were formed being in a pool full of chemicals. But eventually, some of the Protein teams and the RNA teams became fast enough to keep producing at a pace faster than their death. They became stable in that environment and started fighting off other chemicals together to survive themselves.

This is a chicken and egg problem. When we look at life today, it consists of both Genetic language and Cellular modules. Both have a co-dependent relationship and we will understand this better going forward.

While there is an edge towards the RNA world theory,

  • RNA acts both as an informational molecule and a biocatalyst, while Protein has almost limited ability to transmit information.
  • RNA can perform the chemistry required for self-replication
  • It is easier to imagine that only one of the complex organic compounds came into being and then evolved than to imagine that both Protein and RNA came into existence around the same place. Though from whatever I have read, for the duration of early Earth, I think both Protein and RNA could have independently formed. They may have then found each other or started to co-depend on each other.
  • Ribosome uses RNA catalysis in currently all known life-forms. It is expected that this process trace back to the Last Universal Common Ancestor(LUCA), or our first grandparent that started evolution.
  • A large number of activities for survival, that is not needed but were relevant 3.5 Billion years ago have been found in RNA.
  • RNA has the features of continuity, to evolve into the current biology

Scientists continue to search for evidence that shows where life emerged, which was the first living organism that satisfied all of the conditions laid down to be defined as life. but the story of how life can be formed is far more clear in the last couple of centuries. There is a good possibility that we may get closer to that answer within the span of our lives.

Non-Cellular Life

Let’s take a moment to talk about Viruses again. One of the reasons why a virus is considered on the borderline of a living-being is because of a couple of reasons. One, Science constantly updates the definitions of what we categorize as life. Two, we learn new information about the chemistry and biology of living-beings.

So a virus is a genetic material floating around inside a protein container, much like I keep the leftover noodles in a plastic container before putting it in the fridge.

But there are also Viroids, which are even missing the container. They are just noodle-like strands of Genetic material, that float around to infect an animal host. They are a blast from our RNA world, only genetic material. Even once inside the host, they have no code to demand the generation of a protein also, but they will capture the host and demand it generates more of its kind, just more RNA strands.

This is similar to how Pluto was earlier classified as a planet. Then as we observed for longer and got more information, we realized in some cases, it does not act as a planet. So either we change our definition of a planet or just stop classifying Pluto as a planet. We chose the easier option, and instead of redefining the definition of a planet, we chose to remove Pluto and have one less planet in our Solar System. Did anything really change? Pluto still orbits the Sun in the same amount of time. It is still physically present at the same place it earlier was. It still exists and is still a part of our Solar System. There has been no effect on Pluto, due to our change in definition.

So definitions are made by humans, the physical world does not really change with the definitions. While it is easier to describe Earth 🌍 as a planet, Pluto is not the same case. Similarly, a virus has genetic material. Given a host, it can reproduce, but it can’t control metabolism inside its own body. It does not even have a cell, that classical biology used to describe as the basic building block of life.

But we can choose to recognize non-cellular genetic material also like life. It can’t produce proteins and can’t replicate without external help. But then, will we also apply the same definition to a computer printed RNA vaccine? Should we classify it as life?

These are hard questions, as they are as much philosophical as they are scientific. But no matter the definition, the fact that a virus has a genetic material without a cell, and can reproduce given the right external environment will not change.

Cellular Life

So somehow between the RNA world and the protein world, the viroids and the virus, an even more complex organism is created. We know it as Cell.

A cell is the smallest unit of life. They are called the building blocks of life. A human body has 200 different types of cells, Lego, on the other hand, has 2,350 different variants. While you can pretty much make the same things from Lego blocks, they don’t look as good.

Also, Lego people can’t make new lego people, or protect themselves, or need energy. They just sit there doing nothing, unlike our Batman which ventures out every night to protect Gotham.

So the Cell is a very complex organism. Much more complex than a protein, or an RNA, or a virus. The chemical teams that were trying to survive, managed to put aside their differences and formed a larger team. The RNA team and the protein team got together and made a pact to help out each other. This would help them fight other chemicals and become stronger.

But they still had problems. Simple chemicals would attack parts of the Cell which were unprotected and the entire machinery would break down. This meant that even though they were a team, each one had to constantly keep fighting off individual chemicals. Some of the Amino Acids were also scared of water. And given they were in deep underneath the surface of the ocean, they would die or just not be able to perform. Some had a problem with magnesium, others had a problem with acidic chemicals. Sometimes a protein would spend energy and break up a complex molecule, but before it could use it, it would either float away or some other chemical would grasp that molecule.

Also, it was hard to work as a team without having a space of their own. They were kind of living on the street, or rather in the ocean. But they were still looking for new teams to join them. They wanted to make a dent in the Universe and making a larger team was now part of their strategy. They had realized that working with teams was better than working alone. The more teams they could create or convince to join them, the stronger they would get.

They had noticed another complex molecule swimming around in the ocean. Earlier they used to ignore that molecule, as it looked Fat and did not seem very useful. They even had a nickname for it, Fatty Acid. They noticed that Fatty could take different shapes like them. They knew they had to get Fatty onboard with their plan to become the most complex and survivable team. They persuaded the Fatty Acid to join their team. They told Fatty, it would also get the molecules it requires to keep in shape. Working with the team will also ensure enough exercise for Fatty to be fit.

As the organism became more complex, it needed security. So it marked its territory and took the job of protecting all the chemicals inside so that they can keep doing their jobs. One day while gazing out in the ocean they saw a Fatty Acid form a circle-like shape. They asked Fatty if it can mark territory and create a border for the team. With Fatty Acid they now had a private place to live. Fatty created a border around the cell, Cell Wall.

Fatty Acid

But the cell used to get deflated due to the empty space inside. So it filled the entire area inside the boundary with water, salt and proteins. It helped in keeping the shape of the cell and also providing a gel-like atmosphere for all different components to move around. It called this the Cytoplasm.

They had also found that Sugar molecules, were helpful in the generation of energy. Given that Team Cell now looked more like a city, rather than a small house. The cell needed more energy to keep growing and to perform higher-level functions.

After assembling an extraordinary team, recruiting new members, and creating a safe space. They decided to take a team Selfie.

A cell

Proteins became specialists in everyday functions. They would take in complicated chemicals or macromolecules and break them into simpler parts, or monomers. Then you could form macromolecules of its own need, from these monomers. They would ensure the cell is kept in shape. They became experts at metabolism. They would build the Cell walls. Security was transferred to their domain.

In this entire process, there was also the formation of new Genetic material, the DNA. As both the RNA team and the Protein team came together, the responsibilities became more specialized. RNA became in charge of which proteins to be generated, and then the proteins would take care of the rest of the body.

Initially, RNA was storing all the information. But now it was put in charge of management and strategy. RNA suddenly had more work, and it chose to take a step back from some of its earlier functions that Proteins could perform better. It became in charge of storing the entire information. But there were complications. Remember the special bonds AU and CG. These were starting to become a problem. RNA would write down something and sometimes bonds would form between its individual bases, and that would make the older structure and thus the information illegible. It realized it can’t have such an unreliable method to store information. So it decided to start forming Double-Helix Chains. This meant every teammate already gets a partner. These partner pairs were named Base-Pair. The new chains were named as Deoxyribonucleic Acid or DNA.

It also decided to add a new member to its team, Thymine or T. It went and had an awkward chat with Uracil. It told Uracil, that Thymine will be part of the new DNA team. It would still need Uracil to be a part of the RNA team. Uracil was having a lot of fun now that the cell was so big and luxurious. It did not want to go back alone in the dark volcanic vents. It accepted the decision and decided to hang around with others.

The Cell members got together and decided it was time to more clearly define their new roles and responsibilities. It was getting very confusing and they decided to call a Cellhall meeting. A copy of the minutes is being shared for everyone to read

  • It is decided that each of the important chemical teams will now be called Biomolecules. We have passed the stage when we were just chemicals like the rest and the field of study should be called Biology.
  • Carbohydrates or Sugars
    • Sugar has the primary responsibility to produce energy.
    • Create short-time energy storage. While we will refill your supplies but we may need energy at odd times.
    • Help in building other Macromolecules like Ribose and DNA
    • Energy is extremely important, do not let us run out.
  • Lipids or Fats
    • Lipids will be responsible for ensuring long term storage of energy. In case Carbs is slacking, you become the source of energy. We can not run out of energy, or else the whole city will die.
    • Responsible for maintaining a perimeter around the Cell. Create borders, setup walls and ensure passage in and out only after checking papers.
    • Ensure the structural integrity of the Cell.
    • You will be assigned more responsibility as we go forward.
  • Proteins
    • Proteins have been the backbone of our Cell. You have got a good team of different Amino Acids going. Given the versatile team, you are going to be the primary worker.
    • When we get new complex compounds, break them down into simpler compounds. Use those simpler compounds to build back complicated ones we need.
    • If some invader enters the city, take care of it.
    • Reflect the pulse of the city if it is sad or happy.
    • We will discuss more specialized roles for each type of worker based on their ability in the next meeting.
  • Nucleic acid or Genetic Material
    • RNA and DNA are now in charge of information storage for the entire city. Ensure that the information is never lost.
    • Store all the minutes of the meeting when important decisions are made, including this one.
    • Create and store manuals on the creation of proteins. Ensure that instructions of the manual are followed.
    • Keep a record of experiments, which ones were successful and which ones failed.
    • Pass the manuals to the Ribosome when we need to create new proteins. Lend a hand and pass on amino acids to create proteins.
    • More specialized responsibilities will be detailed out in the next meeting.
  • Ribosome
    • Ribosome will produce more workers or proteins. Ensure we are never short.
    • Give a shout out the Genetic material, if you need any information or raw material.
  • Everyone else, you will get your instructions from the Genetic Material. If new and important developments take place, we will do another Townhall.
  • This meeting is over. Go team Cell!!
Prokaryotic Cell

A cell remains the basic building block of life as we know it. The cell is an extremely complex organism, making sure each of the biomolecules inside keeps doing its job.

Life did not emerge one day out of thin air. It has been an evolutionary process. Where we stop and say life has started is upon us to choose. Would a strand of RNA, that relies on another host be considered life? What is that RNA strand could change shape to survive in the environment? Would a Cell, which relies on just eating chemicals be considered life? Based on the definition we choose, the point of origin of life changes.

Since the formation of the first cell, the Genetic material has tried millions of experiments to evolve. Some experiments of the genes were successful and it got a chance to build upon the previous experiments. In most cases, experiments failed and that marked as the death of that species.

And over this period, chemicals learned to produce more of themselves and pass on valuable information to the next generation. Just as humans had a hard time and were able to make little progress without having a language, biomolecules had a hard time before Genetic language. But we have seen that progress in generations is exponential.

In this part, we looked at the story of the formation of genes, from a spec of nothing. How chemicals in the universe have been increasing their complexity since the start of the Universe. But this is just the beginning of the story. DNA is one of the most complex and the longest molecule in existence and it is just getting started.

In the next part, we will dive deeper into Genes, Reproduction, Mutation, and Evolution. How a single cell, produces all the biodiversity that is around us? How different configurations of Proteins, can help a species adapt to its environment? What can gene editing achieve? This is Genetic Engineering by nature.

The last part will focus on the field of Genetic Engineering, driven by humans. The Human Genome Project and CRISPR. How far are we from superhumans? How Gene editing can help eradicate hereditary diseases and give immunity to humans from common diseases?

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