What is DNA?
Deoxyribonucleic Acid (DNA) is the language used for the blueprint of an organism. It is a digital code, in some ways similar to the sequence of 0s and 1s used in binary computer code. For example, in binary coding, the sequence 0-1-0-0-0-0-1-0 represents the letter “B” whereas 0-1-0-0-1-1-0-1 represents the letter “M”. DNA, on the other hand, makes use of 4 different chemicals called nucleotides, which code for a vast multitude of organic compounds which make us.
What is DNA made of? How is DNA structured?
The nucleotides in DNA are chemical compounds of carbons, nitrogens and phosphate groups. Adenine, Thymine, Guanine and Cytosine are the 4 nucleotides which comprise the DNA code abbreviated by A, T, G and C. A’s bind with T’s and G’s bind with C’s making the DNA sequence complementary. The DNA is structured in a double helix which allows a process of unravelling. Taken together, this structural arrangement, immediately indicates a mechanism for DNA’s potential for duplication and therefore heritability.
What does the DNA code produce?
The sequence of As, Ts, Gs and Cs along the DNA double helix determines which amino acid is produced, and subsequently which protein is produced in response to chemical cues and cellular messengers. For example, the DNA sequence T-A-T codes for the production of the amino acid Tyrosine and T-G-G codes for the amino acid Tryptophan. Amino acids are biological compounds composed of carbon, hydrogen, oxygen and nitrogen. In humans there are 20 amino acids coded by various 3-letter combinations of As, Ts, Gs and Cs and are the building blocks of proteins. A linked chain of amino acids is what forms proteins.
What is the function of these proteins?
There are hundreds of thousands of proteins in the human body which are folded into precise 3D shapes. Proteins perform a huge array of functions in the human body. They play a major role in the scaffolding and structure of all cells. Most enzymes (biological molecules which aid biochemical reactions) are made of proteins. A few other functional roles of proteins include the formation of hair cells, muscle fibers, neurotransmitters and are the single constituents of ion channels and receptors found in nerve cells.
What is a gene? What is the genome?
A sequence of DNA which is heritable and performs a particular function, producing a particular protein, is termed a gene. There are approximately 20,500 protein coding genes in humans. The totality of genes in an organism is termed the genome. The genome is densely packed with information on how the body and its various organs and individual cells grow and function. In humans, the genome contains roughly 700mb of data weighing about 0,000,000,000,006 grams and if unravelled and stretched out, is about 2.5 metres long.
How is DNA packaged?
Because DNA is incredibly small and tightly bound this allows the complete DNA of the organism to be contained in each cell of your body. It is housed in the nucleus of a cell and repeatedly wrapped in a fractal like pattern allowing for its tiny footprint. The wrapping begins around molecules known as histones, together the DNA and histones make up nucleosomes. The nucleosomes are packaged into a thread and form a fibre known as chromatin. Chromatin is coiled and looped again leading to the final shapes known as chromosomes. Chromosomes are formed around the time two copies of the cells DNA are separated.
How is DNA copied among cells?
Humans, begin as a single cell – a sperm-fertilised-egg containing half the genetic information from the father and half from the mother. As development proceeds, cellular division takes place. The DNA is first duplicated in the parent cell before dividing into 2 daughter cells. These daughter cells themselves divide into 4 and so on. The DNA is duplicated through biochemical nanomachines. Helicase unwinds the DNA into two strands fast as a jet engine. One strand is copied continuously, the other needs to be copied in reverse.
How does a cell differentiate into a neuron or a cardiac cell?
Once the DNA has been copies, the cells then divide and they may subsequently differentiate into specialised cells and migrate to particular locations according to which genes in the cell are expressed. The activation or expression of genes within the cell is dependent on the chemical environment and messengers which surrounds the cell. Different cells divide at different rates, and cell death takes place to control cell number and dispose of dysfunctioning cells.
How are genes expressed?
The expression of genes, in our computer metaphor, is equivalent to the running of the code. The genes housed in the nucleus of a cell need to be interpreted for the production of proteins or functional Ribonucleic Acids (RNAs). This occurs through the processes of transcription and translation of DNA into RNA and subsequent production of proteins. RNA is chemical cousin of DNA made up of As, Us (not Ts), Gs and Cs and can be thought of as the major group of molecules involved with interpretation and communication of the primary DNA store.
Gene expression begins when a chemical signal derived inside or received from outside the cell triggers a cascade of intracellular signalling and events. The “transcription” phase of gene expression begins with “initiation”. Intracellular signalling in the form of transcription factors bind to and regulate an enzyme called DNA polymerase which itself attaches to a specific promoter region of DNA dependent on the transcription factors. Once attached “elongation” begins where the RNA polymerase complex, acts like a zipper, and slides along the DNA and unwinds the DNA making a copy of the template strand of DNA. This occurs through free-roaming As, Us, Gs and Cs which bind to the coding strand and create the messenger RNA (mRNA) in the process. As the DNA polymerase slides along the DNA, it unwinds the DNA at the front and stitches up the DNA at the back, until it reaches the specific terminating region and detaches from the DNA completing the “termination” phase. The RNA produced here, may be subject to further processing such as “splicing” where some introns (non-amino-acid coding regions of DNA) may be removed placing the exons (amino-acid coding regions of DNA) adjacent to each other.
Once the mRNA has been completed it travels outside the nucleolus and through a pore in the nuclear envelope where it binds with ribosomes. Ribosomes are the protein making machinery found in cells. The mRNA is fed through the ribosomes like ticker-tape and the process of “translation” begins. Free roaming transfer RNA (tRNA) are 3-letter RNA molecules which attach to the coded amino-acid. While the mRNA is being fed through the ribosome, when the correctly corresponding tRNA / amino acid complex binds to the currently processed mRNA code section, the tRNA disperses, and the amino acid is sequentially added to the linked amino acid chain forming the protein. Once the protein is made it is chaperoned to a machine where the protein is folded into a particular shape. The protein is then released into the cell and potentially transported in vesicles to its intended destination. This process is happening in billions of your cells at any given moment.
The central dogma of molecular biology
These described processes form the central dogma of molecular biology as suggested by Francis Crick in 1970. DNA replicates to make more DNA –> RNA is produced through transcription of the DNA –> RNA is translated into protein –> Proteins make us.
I have now explained the fundamental tenets of molecular biology. It’s remarkable how a set of signaling, encoding, decoding, manufacturing and logistic operations are able to explain our fundamental biological workings. However, these operations are special in that they take place at an unimaginably tiny scale with vast amounts of detail and depth. Perhaps the most remarkable aspect of this system is that what it assembles, has come to understand it.
I highly recommend watching these videos for a fuller and added dimension of understanding.
References and Image Sources:
- “Cell and Molecular Biology” course, University of Otago, 2009
- “The Central Dogma of Molecular Biology”, Crick, 1970
- “Direct Imaging of DNA Fibers: The Visage of Double Helix”, Gentile et al., 2012
- “The Structure of DNA”, Watson & Crick, 1953
- “Transcription regulation and Animal Diversity”, Levin & Tijan, 2003
- “The sequence of the Human Genome”, Venter et al., (2001)