Cracking the genetic code

In the same way that Alan Turing decoded Enigma, the encryption machine used by the German army in World War II, several scientists managed to decipher the genetic code. The solution to this framework has allowed us to understand how cells work and make genetic manipulation possible.

INTRODUCTION

A code is a system of replacing the words in a message with other words or symbols, so that nobody can understand it unless they know the system. For example the genetic code.

Although it seems to be a lie, all living beings (except for some bacteria) biologically work in the same way. And it is that Jacques Monod already said, everything that is verified as true for E. coli must also be true for elephants.

From the cells of the blue whale, the largest animal on the planet, to the cells of a hummingbird, passing through humans, are the same. This is thanks to the genetic code, which allows the information of each gene to be transmitted to the proteins, the executors of this information.

This flow of information was named by Francis Crick, in 1958, as the central dogma of molecular biology (Figure 1). In it he claimed that information flows from DNA to RNA, and then from RNA to proteins. This is how genetic information is transmitted and expressed unidirectionally. However, later modifications were added. Crick claimed that only DNA can be duplicated and transcribed to RNA. However, it has been seen that the replication of its RNA also occurs in viruses and that it can perform a reverse transcription to generate DNA again.

Figure 1. Central dogma of molecular biology. Red arrows: Francis Crick’s way. Grey arrows: later modifications (Source: Quora)

THREE LANGUAGES OF CELLS

Inside the cells three different languages ​​are spoken, but they can be related through the genetic code.

The one we already know is the language of deoxyribonucleic acid (DNA), wound in a double chain and composed of 4 letters that correspond to the nitrogenous bases: adenine (A), thymine (T), cytosine (C) and guanine (G).

Another language very similar to the latter is that of RNA. It differs from DNA mainly in three aspects: (i) it is composed of a single chain instead of being double-stranded, (ii) its sugars are ribose instead of deoxyribose (hence the name of ribonucleic acid) and (iii) it contains the base uracil (U) instead of T. Neither the change of sugar nor the substitution of U by T alters the pairing with base A, so that RNA synthesis can be performed directly on a DNA template.

The last language that remains for us to know is that of proteins, formed by 20 amino acids. The amino acids constitute each and every one of the proteins of any living organism. The order of the amino acids that form the chain of the protein determines its function (Figure 2).

Figure 2. Table of 20 amino acids (Source: Compound Interest)

THE GENETIC CODE

As we have been saying, the genetic code is the rules that follow the nucleotide sequence of a gene, through the RNA intermediary, to be translated into an amino acid sequence of a protein. There are several types of RNA, but the one that interests us is the messenger RNA (mRNA), essential in the transcription process.
The cells decode the RNA by reading its nucleotides in groups of three (Figure 3). Since mRNA is a polymer of four different nucleotides, there are 64 possible combinations of three nucleotides (4³). This brings us to one of its characteristics: it is degenerate. This means that there are several triplets for the same amino acid (synonymous codons). For example, proline is coded by the triplets CCU, CCC, CCA and CCG.

Figure 3. The genetic code with the table of 20 amino acids (Source: BioNinja)

The genetic code is not ambiguous since each triplet has its own meaning. All triplets make sense, either encode a particular amino acid or indicate read completion. Most amino acids are encoded by at least two codons. Methionine and tryptophan are the only amino acids that are codified only by a codon. But each codon codes only for an amino acid or stop sign. In addition, it is unidirectional, all triplets are read in the 5′-3′ direction.
The AUG codon serves as the start codon at which translation begins. There is only one start codon that codes for the amino acid methionine, while there are three stop codons (UAA, UAG and UGA). These codons cause the polypeptide to be released from the ribosome, where the translation occurs.
The position of the start codon determines the point where translation of the mRNA and its reading frame will begin. This last point is important because the same nucleotide sequence can encode completely different polypeptides depending on the frame in which it is read (Figure 4). However, only one of the three reading patterns of a mRNA encodes the correct protein. The displacement in the reading frame causes the message no longer to make sense.

Figure 4. Possible frameshifts (Source: marcoregalia.com)

 

As we said at the beginning, one of the main characteristics of the genetic code is that it is universal, since almost all living beings use it (with the exception of some bacteria). This is important because a genetic code shared by such diverse organisms provides important evidence of a common origin of life on Earth. The species of the Earth of today probably evolved from an ancestral organism in which the genetic code was already present. Because it is essential for cellular function, it should tend to remain unchanged in the species through the generations. This type of evolutionary process can explain the remarkable similarity of the genetic code in present organisms.

Although the human being itself continues to be an enigma for science, the revolution of the deciphering of the genetic code has allowed us to delve into the functioning of our body, specifically that of our cells, and cross borders to genetic manipulation.

 

REFERENCES

• Alberts, B. et al. Biología molecular de la célula (2010). Editorial Omega, 5a edición
• Cooper, G.M., Hausman R.E. La Célula (2009). Editorial Marbán, 5a edición
• Gotta Love Cells
• BioNinja
• Main picture: eldiario.es

Tardigrades: animals with superpowers

The smallest bears in the world have almost superhero abilities. Actually, they are not bears: water bears is the popular name of tardigrades. They are virtually indestructible invertebrates: they can survive decades without water or food, to extreme temperatures and they have even survived into outer space. Meet the animal that seems to come from another planet and learn to observe them in your home if you have a microscope.

WHAT IS A TARDIGRADE?

Water bear (Macrobiotus sapiens) in moss. Colored photo taken with a scanning electron microscope (SEM). Photo by Nicole Ottawa & Oliver Meckes

Tardigrades or water bears, are a group of invertebrates 0.05-1.5 mm long that preferably live in damp places. They are especially abundant in the film of moisture covering mosses and ferns, although there are oceanic and freshwater species, so we can consider they live anywhere in the world. Even a few meters away from you, in the gap between tile and tile. In one gram of moss they have find up to 22,000 individuals. They are found in Antarctica under layers of 5 meters of ice, in warm deserts, hot springs, in mountains 6,000 meters high and abyssal ocean depths: they are  extremophiles. It is estimated that over 1,000 species exist.

MORPHOLOGY

Its popular name refers to their appearance, and the scientific name to their slow movements. Their bodies are divided into five segments: cephalic, with its tube-shaped mouth (proboscis) with two internal stilettos and sometimes simple eyes (ommatidia) and sensory hairs, and the remaining 4 segment with a pair of legs per segment. Each leg has claws for anchoring to the ground.

Bottom view of a Tardigrade where the five segments of the body are observed. Colored photo taken with a scanning electron microscope (SEM). Photo by Eye Of Science/Science Photo Library

Tardigrade (Echiniscus sp.) In which you can see the claws. Colored photo taken with a scanning electron microscope (SEM). Photo de Eye Of Science/Science Photo Library

Look at this video of Craig Smith to see tardigrade’s movements in more detail:

FEEDING

With its mouth stilettos, tardigrades perforate plants and absorbe the products of photosynthesis, but they can also feed absorbing the cellular content of other microscopic organisms such as bacteria, algae, rotifers, nematodes… Some are predators too and can eat whole microorganisms.

Their digestive system is basically the mouth and a pharynx with powerful muscles to make sucking motions that opens directly into the intestine and anus. Some species defecate only when they shed.

Detail of the mouth of a tardigrade. Colored image of scanning electron microscope (SEM). Photo by Eye Of Science/Science Photo Library

INTERNAL ANATOMY

They have no circulatory or respiratory system: gas exchange is made directly by the body surface. They are covered by a rigid cuticle which can be of different colors and is shed as they grow. With each moult, they lose oral stilettos, to be segregated again. They are eutelic animals: to grow they only increase the size of their cells, not their number, that remains constant throughout life

REPRODUCTION

Tardigrades generally have separate sexes (are dioecious) and reproduce by eggs (are oviparous), but there are also hermaphrodites and parthenogenetic species (females reproduce without being fertilized by any male). Fertilization is external and development is direct: they don’t have larval stages.

Tardigrade egg. Colored image of scanning electron microscope (SEM). Photo by Eye of Science/Science Photo Library

TARDIGRADE’S RECORDS

The tardigrades are incredibly resilient animals that have survived the following conditions:

• Dehydration: they can survive for 30 years under laboratory conditions without a single drop of water. Some sources claim that resist up to 120 years or have been found in ice 2000 years old and have been able to revive, although it is likely to be an exaggeration.
• Extreme temperature: if you boil one tardigrade survives. If you put it to temperatures near the absolute zero (-273ºC), survives. Their survival rate ranges from -270ºC to 150ºC.
• Extreme pressure: they are capable of supporting from vacuum to 6,000 atmospheres, ie 6 times the pressure in the deepest point on Earth, the Mariana Trench (11,000 meters deep).
• Extreme radiation: tardigrades can withstand bombardment of radiation at a dose 1000 times the lethal to a human.
• Toxic substances: if they are immersed in ether or pure alcohol, survive.
• Outer space: tardigrades are the only animals that have survived into space without any protection. In 2007 the ESA (European Space Agency) within the TARDIS project (Tardigrades In Space) left tardigrades (Richtersius coronifer and Milnesium tardigradum) for 12 days on the surface of the Foton-M3 spacecraft and they survived the space travel. In 2011 NASA did the same placing them in the outside of the space shuttle Endeavour and the results were corroborated. They survived vacuum, cosmic rays and ultraviolet radiation 1,000 times higher than that of the Earth’s surface. The project Biokis (2011) of the Italian Space Agency (ASI) studied the impact of these trips at the molecular level.

HOW DO THEY DO THAT?

The tardigrades are able to withstand such extreme conditions because they enter cryptobiosis status when conditions are unfavorable. It is an extreme state of anabiosis (decreased metabolism). According to the conditions they endure, the cryptobiosis is classified as:

• Anhydrobiosis: in case of environmental dehydration, they enter a “barrel status” because adopt barrel shaping to reduce its surface and wrap in a layer of wax to prevent water loss through transpiration. To prevent cell death they synthesize trehalose, a sugar substitute for water, so body structure and cell membranes remain intact. They reduce the water content of their body to just 1% and then stop their metabolism almost completely (0.01% below normal).

  

  Tardigrade dehydrated. Photo by Photo Science Library

• Cryobiosis: in low temperatures, the water of living beings crystallizes, it breaks the structure of cells and the living being die. Tardigrades use proteins to suddenly freeze water cells as small crystals, so they can avoid breakage.
• Osmobiosis: it occurs in case of increase of the salt concentration of the environment.
• Anoxybiosis: in the absence of oxygen, they enter a state of inactivity in which leave their body fully stretched, so they need water to stay perky.

Referring to exposures to radiation, which would destroy the DNA, it has been observed that tardigrades are able to repair the damaged genetic material.

These techniques have already been imitated in fields such as medicine, preserving rat hearts to “revive” them later, and open other fields of living tissue preservation and transplantation. They also open new fields in space exploration for extraterrestrial life (Astrobiology) and even in the human exploration of space to withstand long interplanetary travel, ideas for now, closer to science fiction than reality.

ARE THEY ALIENS?

The sparse fossil record, the unclear evolutionary relatedness and great resistance, led to hypothesis speculating with the possibility that tardigrades have come from outer space. It is not a crazy idea, but highly unlikely. Panspermia is the hypothesis that life, or rather, complex organic molecules, did not originate on Earth, but travelled within meteorites in the early Solar System. Indeed, amino acids (essential molecules for life) have been found in meteorites composition, so panspermia is a hypothesis that can not be ruled out yet.

Photo by Eye Of Science/Photolife Library

But it is not the case of tardigrades: their DNA is the same as the rest of terrestrial life forms and recent phylogenetic studies relate them to onychophorans (worm-like animals), aschelminthes and arthropods. What is fascinating is that is the animal with more foreign DNA: up to 16% of its genome belongs to fungi, bacteria or archaea, obtained by a process called horizontal gene transfer. The presence of foreign genes in other animal species is usually not more than 1%. Could be this fact what has enabled them to develop this great resistance?

DO YOU WANT TO SEARCH TARDIGRADES BY YOURSELF AND OBSERVE THEM IN ACTION?

Being so common and potentially livIng almost anywhere, if you have a simple microscope,  you can search and view living tardigrades by yourself:

• Grab a piece of moss of a rock or wall, it is better if it is a little dry.
• Let it dry in the sun and clean it of dirt and other large debris.
• Put it upside down in a transparent container (such as a petri dish),  soak it with water and wait a few hours.
• Remove moss and look for tardigrades in the water container (put it on a black background for easier viewing). If lucky, with a magnifying glass you’ll see them moving.
• Take them with a pipette or dropper, place them on the slide and enjoy! You could see things like this:

REFERENCES

• Pequeños pero invencibles
• Revelan más secretos del indestructible tardígrado
• Meet the miniature water bear: nature’s ultimate survivor or an alien from another planet?
• Tardígrados, los animales que desafían toda preconcepción biológica
• Tardigrada.es
• Los tardígrados, ositos de agua
• Tiny animal survive exposure to space
• Anhydrobiosis in invertebrates
• “Alien” water bears amaze scientists
• Tardigrada (Astronoo)
• La criptobiosis en el phylum Tardigrada
• El animal “más resistente de la Tierra” se prueba en el espacio
• Cover photo by Oliver Meckes