The one about Genetic Code
Offspring clearly resemble their parents, and this fact alone means that there must be some biological mechanism of inheritance. The starting point for our modern understanding of that mechanism is provided by experimental crosses between strains of garden pea. The experiments were conducted by Austrian monk, Gregor Mendel.
Mendel began with two pea strains, differing in an observable characteristics such as flower color (one strain had purple, other white, flowers). He crossed them, and the offspring were all purple. He then crossed the offspring among themselves, and found that the second generation had purple and white flowers in 3:1 ratio. He explained the result by suggesting that coloration is controlled by two kinds of ‘factor’; a pea plant inherited one factor from each parent. The purple factor was ‘dominant’ to the white factor, and all the first-generation plants were purple. But a quarter of second-generation plants inherited two white factors and were white.
In Mendel’s peas, the gene responsible for color translates to a protein that directly or indirectly controls the color. In this blog post I hope to explain how this genetic code works. The translation of genetic code from DNA to protein is known as the Central Dogma. Towards the end I will also briefly discuss interesting genetic components like telomeres that determine how much life we have left, Miller-Urey experiment that shows how life can spontaneously form, and epigenetics that show how consequences of our behavior can be passed on to generations.
Proteins are among the most abundant and most diverse organic molecules. Everything in our cells from enzymatic action that break and build other biomolecules to providing structure that give cells shape to signaling between cells and to acting as hormones is carried out by proteins. A single cell can contain thousands of proteins, each with a unique function. Whenever a cell needs a specific protein to perform a job, it transcribes the gene for that protein from DNA to messenger RNA(mRNA) inside the nucleus. mRNA unlike DNA is able to leave the nucleus. Once outside, the mRNA can be translated into a string of amino acids. The chain of amino acid makes a polypeptide which folds into a 3d model of the required protein. For example, Mendel’s flower color gene provides instructions for a protein that helps make colored pigments in flower petals. Some genes also code for functional RNAs(construction workers that build protein from mRNA) like transfer RNA(tRNA), ribosomal RNA(rRNA) etc.This flow of information from DNA to protein is known as the central dogma. Most important point is that the genetic code is universal. Virtually all species use the same genetic code to translate their genes into protein.
DNA is one of the key macromolecules needed to sustain life as we know it. Other macromolecules include protein, carbohydrates, and lipids(fat). DNA bears the hereditary information that is passed down from parents to children. A DNA has the complete set of instructions for building that specific organism.
DNA is composed of a sugar (turquoise pentagon) and phosphate (green circle) backbone with nitrogenous bases (A,C,G,T) sticking out. Together the three molecules make one nucleotide. All the elements needed to build DNA are carbon, oxygen, hydrogen, nitrogen, and phosphorous. Base A always binds to T and C always bind to G. The two strands of helix run in opposite directions(5' →3' and 3' →5'). Having direction is important to ensure DNA is always translated in the same direction or you will get a completely different protein or some gibberish crap.
The Human Genome
The genome is the complete set of genes or instructions needed to make a certain organism(this is you entire DNA). The human body contains approximately 100 trillion cells. Inside each cell is a nucleus and inside each nucleus are two complete sets of human genome(one set from mom and one set from dad). Two exceptions to this are sex cells which have only one copy and red blood cells which have none because they have no nucleus. The human genome contains about 25,000 genes which come packaged in 23 separate pairs of chromosomes(so imagine your entire DNA chopped up in 23 parts). The number 23 is of no significance. Many less complex species have more chromosomes than us. In 2003, the Human Genome Project successfully mapped all genes found on human DNA.
If I read the genome out to you at the rate of one word per second for eight hours a day, it would take me a century. This gigantic document fits inside the microscopic nucleus of a tiny cell that fits easily upon the head of a pin.
The Genetic Code
Cells decode mRNA by reading nucleotides in groups of 3 called codons. The relationship between codons and amino acids is the genetic code. Most codons specify an amino acid(notice there are several ways to code one amino acid). There is also one start codon — AUG , which codes for methionine(all proteins start with this amino acid) and 3 stop codons — UAA, UAG, UGA which indicates where to stop translation.
THE PROCESS
Transcription = DNA →mRNA
The DNA sequence of a gene is transcribed into RNA. In eukaryotes(cells with nucleus), this RNA must undergo further processing to become mature RNA (mRNA). There are two complementary strands of DNA in a double helix. The non-coding strand acts as a template for the synthesis of a complementary RNA strand. This process is initiated by an enzyme called RNA polymerase. Once the RNA polymerase attaches to the promoter site, translation can proceed. This RNA strand has the same information as the coding strand. One important difference is that in RNA nucleotide T is replaced with U. In bacteria, protein can be translated from this RNA but in eukaryotes RNA is converted to mRNA by adding a cap at the start and tail at the end of the strand. Genes also have junk sequence called introns inserted between the coding sequences known as exons. During the mRNa maturing process the introns are spliced and exons are stitched together. If the introns are not removed, they’ll be translated along with the exons, producing a “gibberish” polypeptide.
Translation = mRNA →Protein
During translation, the nucleotide sequence of an mRNA is translated into the amino acid sequence of a protein. Translation takes place inside the polypeptide building molecular machine called ribosomes. Once a ribosome latches on to an mRNA and finds the “start” codon, it will travel rapidly down the mRNA, one codon at a time. The right amino acid is brought to the ribosome by tRNA. Imagine tRNA as the key to the specific codon and once it fits, tRNA lets go of the amino acid which gets added to the chain. This process repeats many times, with the ribosome moving down the mRNA one codon at a time and new tRNAs bringing the completmentary amino acid. Translation ends when the ribosome reaches a stop codon and releases the polypeptide.
PROTEIN FOLDING
Once the polypeptide is finished, it will be folded into a 3D protein then shipped to a specific destination inside or outside the cell(the shipping machines are made out of proteins as well!). Ultimately, it will perform a specific job needed by the cell or organism — perhaps as a signaling molecule, structural element, enzyme, or hormone. For example, insulin is a protein whose 3 d structure allows it to open cell doors for glucose. The folding of peptide into a 3d protein is an extremely complex task that our body does with great ease. In fact a peptide sequence had more ways it can fold than number of stars in the known universe. Protein folding has been a problem that computers have been trying to solve for decades. Until this year when Google’s artificial intelligent computer, Alpha fold had a huge breakthrough! Did you know until today insulin for medical use is produced by injecting e.coli with the gene for insulin. Then we hijack its genetic machinery to fold the final product in the right 3d structure.
DNA REPLICATION
This is the process by which a cell makes an identical copy of the entire genome during cell division. This is done when you need brand new cells and not just component proteins. This is no easy task considering you are trying to accurately copy 3 billion base pairs. So, many enzymes are involved in making this process as smooth and errorless as possible.
Here are some of the key players:
DNA helicase — it’s an enzyme that starts off the process by unzipping the double helix by breaking the hydrogen bonds joining two nucleotides.
Topoisomerase — this enzyme prevents the double helix in front of the helicase from being too wound up (supercoiling) by releasing the tension.
DNA polymerase — The main player that actually adds new complementary neucleotides to each opened up strand. But it only adds in 5' →3' direction. What this means that is one strand is able to be formed continuously but the 3' →5' strand is made in bits called Okazaki Fragments.
MORE INTERESTING STUFF!!!!
TELOMERES
All DNA begin and end with the same sequence repeated thousands of times. This repeated sequence of TTAGGG is called telomere. These sequences act like caps that protect the internal information. Some information on tips of DNA is lost during each replication. So telomeres are there to ensure that we only loose insignificant code when we replicate. Once you run of telomeres, you can’t safely divide your cells anymore. Cells don’t generally need to divide unless you are growing or have damaged your cells (accidents, smoking, UV radiation). On average cells will divide about 60 times before they run out of telomeres. This usually indicates end of life. Older people will have shorter telomeres than younger people. By studying someone’s telomeres we can calculate their age and lifetime. There’s an enzyme called telomerase that adds telomeres back to DNA. It’s present in stems cells that can divide forever. But the enzyme is turned off in adults. It’s an evolutionary compromise that stops cells growing out of control and turning into cancer. In 2010, Harvard scientists were able to reverse aging in mice by injecting them with telomerase. If injections are given periodically to humans and given at a younger age when they are at less risk for developing cancer, this would reverse aging
EPIGENETICS
Genes in chromosomes are rolled up in histones like threads on a spool. If a gene is read more often than others then it will be loosely packed compared to other genes. A gene can also be turned on or off by adding certain molecules on it. How often a gene is translated depends on your behavior and environment and not just your actual genetic code. DNA stores memory of these “modifications” to your genetic code made by you lifestyle and environment. It’s not a change in your genetic code, but a change in how a gene is read. And these changes can be passed on to next several generations. This means consequences of our diet and effects of pollution can be passed on to our children. This is called Epigenetics. Essentially epigenetics is turning on/off of genes. Since all our cells have all our DNA, epigenetics is important because we wouldn’t want our muscle cells to make bone cells. But unfortunately this also means that the cigarette you smoke is causing an epigenetic change silencing the tumour suppressor gene. And this can be passed down generations.
DNA as a Hard Drive
DNA acts as the ideal hard drive that can store more information in its tinyyyyyy body than any other current storage devices. And it can be preserved for millions of years. This is not a theory anymore but a fact made possible by scientists across the globe. The first successful attempt at this was when a team of researchers stored a gif of a galloping horse on an E.Coli DNA.
Abiogenesis — 1952 Miller-Urey experiment
Abiogeneis is a theory that life arrived spontaneously from nonliving organic matter. In the famous Miller-Urey experiment, scientists recreated the environment when first life may have formed in the hydrothermal vents of earth’s oceans. By adding energy to a constituent of early earth’s molecules(H2O, CH4, NH4, N2) Miller’s experiment resulted in spontaneous formation of building blocks of life including amino acids, sugars, and lipids. Life starting spontaneously seems farfetched to some people but when given millions of years of molecules joining in different combinations, forming the building block of life is just a matter of time and probability.
And that’s all the important things we need to know to about our genetic code. Hope you found it informative and interesting. Until next time :)
References: Figures — khancademy .org ; Numbers — Genome by Matt Ridley
