In this article Dr. Anant Jani explains some of the concepts behind the common-used (and often only vaguely understood) language in the study of genetics – and explores some of the fascinating questions that we still need to answer.
Anant is studying for a Bachelor’s degree in Medicine and Surgery at Somerville College, University of Oxford. He has a Ph.D. from Yale University (School of Medicine) and specialises in Immunobiology. At Greene’s, he teaches the U.S. SATs and A levels in Biology and Chemistry.
Genes, genetics, DNA, mutations – these terms are ubiquitous in the media but do we really know anything about them? In this article I hope to take the reader along on a journey to explore what these terms mean, why they are relevant, and why they are fascinating.
Let’s start by going over some basic definitions:
DNA is a chemical; its name stands for DeoxyriboNucleic Acid. Deoxyribose is the sugar component of DNA that lends stability to the overall DNA structure; the nucleic acid is the component that serves as part of the code that specifies what protein a particular gene encodes for.
Nucleic Acid: there are four nucleic acid subtypes used in DNA: Adenine (A), thymine (T), guanine (G), and cytosine (C). Various triplet combinations (called codons) of A, T, C and G code for different amino acids. For example, a DNA sequence that consists of the nucleic acids TGG arranged consecutively codes for the amino acid tryptophan (yes, that’s the stuff found in turkey meat that is supposed to make you sleepy). Dozens, usually hundreds, of codons arranged consecutively constitute a gene.
Gene: a combination of codons that code for different proteins.
Mutation: a change in the normal sequence of nucleic acids in a gene.
Genetics: the science of genes.
Gene regulation: how different genes are used to either actively produce proteins or prevent them from being produced.
Amino Acid: amino acids are chemicals, of which there are twenty different subtypes. Amino acids are the basic subunits that combine together to form proteins.
Proteins: there is the nutritional definition which focuses on the content of protein found in various foods but here we are more concerned with what the proteins found in those foods actually do. Proteins are versatile compounds that play many crucial roles in biology – e.g., providing structure, helping to drive chemical reactions, allowing cells to communicate with each other, fighting infections, etc. Proteins consist of dozens, usually hundreds, of amino acids linked together and then formed into different shapes that allow the protein to carry out its function.
With these definitions we can create a framework (outlined below) where we can arrange these components into the integrated process whereby DNA, in the form of genes, serves as the blueprint necessary to build proteins:
– Several nucleic acids linked together form DNA
– Three nucleic acids in a row form a codon, which codes for different amino acids
– Several consecutive codons form genes
– Genes code for a sequence of amino acids
– Several amino acids linked together form proteins
In the realm of physiology, proteins are one of the most critical components in determining how a cell functions. There are certain proteins that will be found in virtually every cell of the body. For example, the process by which energy is derived from glucose is relatively conserved across every cell; therefore, the machinery, largely in the form of proteins, involved in this process is also conserved. At the other end of the spectrum are highly specialized proteins that are only found in specific types of cells; these proteins are essential in giving a cell its identity. Examples include proteins in stomach cells that aid digestion, proteins in heart cells that drive the heart to contract (i.e. beat), proteins in cells of the immune system that allow these cells to fight infections, etc.
The integrity of the gene (i.e. the blueprint) that gives instructions on how to build these proteins is important in ensuring that the proteins that are produced can function properly. A mutation in a gene will change the blueprint of the protein, which means there is a high chance the protein will not be constructed properly and therefore may not function properly; this could have devastating consequences for normal physiological processes. An example of this is mutations that can cause cancer. Toxins, such as those found in cigarette smoke, can lead to DNA mutations, which can change the construction and therefore identity of proteins that regulate how cells respond to growth signals. With the appropriate combination of mutations, cells can override normal growth processes and become cancerous.
Decades of research have gone into understanding mutations and the structure and function of different proteins. Much work still needs to be done in this field to understand better disease processes that stem from mutations and give hope for those suffering from mutation-related diseases.
Inside your cells DNA is housed in a specialized structure called the nucleus. The nucleus has a diameter of about 6 microns (to give you an idea of how small this is, the thickness of human hair is about 60 microns – 10 times larger than the size of a cellular nucleus). Every cell that has DNA has about 6 billion nucleic acids. If you take the length of nucleic acids into account, 6 billion nucleic acids is equivalent to about 2 metres of DNA! Every nucleus inside every cell in your body has 2 metres of DNA crammed into a space about 10 times smaller than the thickness of your hair. Even taking into account how thin DNA is, one can appreciate that the nucleus is extremely crowded, especially when you consider that there will also be millions of proteins in the nucleus too. The extremely crowded cellular nucleus is certainly interesting but it isn’t the most interesting aspect of DNA and genes; that honour is reserved for gene regulation.
In the last section we established that specific proteins are essential in giving different cells their unique identity. If we take the “genes as blueprints” analogy further, it is important to realize that every cell in your body has the exact same DNA content – that means every cell in your body has the exact same blueprints. A heart cell will have the blueprints necessary to make proteins specific to heart cells and it will also have the blueprints necessary to make proteins specific to stomach cells, brains cells, kidney cells, etc. The same goes for kidney cells having blueprints for kidney proteins as well as heart proteins, stomach proteins, brain proteins, etc. This basic principle applies to every cell in the body. Now here comes the fascinating bit. If we take a heart cell as an example, despite having the blueprints for every protein in the human body, the heart cell will only produce heart cell proteins. In the extremely crowded nucleus, how does the heart cell know that it is a heart cell and that it should only produce heart cell proteins? What we know so far is:
– Different cells have unique developmental processes and these processes are important in programming cells to commit to becoming a specific cell type and produce proteins from only a certain subset of genes.
– The location of cells within the body helps to dictate what genes will be used to produce proteins. An interesting question related to this is:
– The location of genes within the three-dimensional nucleus plays an important role in determining whether a gene will be used to produce a protein; thus, in a heart cell, heart cell genes will be located in a location different from liver, kidney, brain, etc. genes. Interesting questions related to this concept are:
Unfortunately the exact mechanisms regulating genes are not fully understood despite being heavily studied within the scientific community. We are, however, slowly inching our way towards a better understanding of gene regulatory processes and hopefully the next generations of well-trained scientists will solve these beautiful and fascinating mysteries.