Understanding Basis Of Evolution
Take a look at the person closest to you. Compare the color of their eyes, the texture of their hair, even the complexion of their skin to your own. Do you notice a lot of differences? Genetic variation accounts for the dissimilarities we observe between individuals—seemingly trivial ones such as the differences in eye, hair, and skin color; more profound (but not necessarily harmful) variances such as the differing blood groups A, B, AB, and O; and some medically significant differences such as susceptibilities to particular diseases and responses to various drugs.
Since I am on the road teaching this week, we will learn about the basis of evolution with excerpts from our book: The Biotech Primer: An Insider’s Guide to the Science Driving the Biotech and Pharma Industries. Find out why mutations are not only essential to genetic variation, but also how they play a role in evolution. Genetic variations impeding survival and reproduction are often wiped from the population, potentially leading to crucial changes in areas like appearance and biology.
Mutations: The Main Spice In Genetic Variation
The genetic differences we see today arose as a result of mutations in the DNA sequence. Mutations can occur by different means, and the outcome for the organism can vary. There are a number of mutations in each and every one of your cells. This is not necessarily cause for alarm—not all mutations are harmful. Mutations can have various effects on the function of a gene and its protein product.
Some mutations are deleterious, damaging the function of the protein encoded for by the mutated gene. However, many mutations turn out to be neutral and have no effect on gene function. How is this possible? Only 1.5% of the human genome actually codes for proteins—the rest of it is non-coding, known as junk DNA. Most of the time that a mutation occurs, it will occur in these non-coding regions and not affect a protein’s structure or function. Mutations may also be neutral due to the redundancy of the genetic code—sometimes slight changes in a gene sequence result in the same protein being produced. In some cases, even if a mutation occurs in a protein-coding region of the genome, the same protein gets made.
Very rarely, mutations can be adaptive and have a beneficial effect on gene function, conferring an advantage on the organism. This is the basis of Charles Darwin’s Natural Selection or “survival of the fittest” theory. Evolution is the natural selection of beneficial changes.
Some mutations are passed on from one generation to another, and some arise during an organism’s life span. Most mutations occur in somatic cells; that is, cells that are not gametes (eggs or sperm). These mutations are called somatic mutations and are not passed on to children. But mutations that do occur in sperm or egg cells, germ line mutations, will be inherited. If the mutation is so severe that an organism cannot survive, that organism does not pass it on to the next generation. Therefore, over time, deleterious mutations exit the gene pool.
Mutations At The Genetic Level
A substitution, or point mutation, results when one base is swapped out for another. If the DNA polymerase enzyme—the enzyme that copies DNA—accidentally places a C where a G should be during DNA replication, the substitution will alter the recipe.
Sometimes DNA polymerase may skip over a base, which is a deletion, or add an extra base to the sequence, which is an insertion. If a mutation goes unrepaired, it results in DNA sequence changes that will then be copied, becoming permanent. Changes in the DNA sequence as a result of errors by the DNA polymerase during DNA replication are rare, but they do happen. This is understandable when you consider the fact that every time a cell divides, it must copy all 3 billion base pairs of DNA in just a few hours! Fortunately, the DNA polymerase also has proofreading ability, so it is able to “catch” and correct most mistakes, but occasionally a mutation goes unrepaired, resulting in DNA sequence changes that will then be copied, becoming permanent.
In addition to errors made during DNA replication, mutations can also result from environmental factors, such as radiation from the sun or x-rays or from chemicals in cigarette smoke.
Monogenic Vs. Polygenic Disease
Mutations play a large part in disease. In a monogenic disease, changes in one gene cause the disease. Examples of monogenic diseases include sickle cell anemia, cystic fibrosis, and Huntington’s disease.
Polygenic diseases are caused by the interactions of many different genes. Polygenic diseases are more common than monogenic diseases and include cancer, heart disease, Alzheimer’s disease, and Parkinson’s disease. Polygenic diseases often have susceptibility genes associated with them that increase the likelihood of the person developing the disease, but do not absolutely predict its development—the ultimate disease outcome will depend on various other genes in the individual’s genome, as well as environmental factors. An example of susceptibility genes is the association of breast cancer with the BRCA 1 and BRCA 2 genes.
Cocktail Fodder: A Few Base Differences
Scientists estimate there is a single base difference per every 3000-5000 bases, which is what makes humans look so different from one another. In essence, all people are pretty much the same—genetically speaking, of course—minus a base difference here and there!
Emily Burke, PhD has worked in biopharma for 20 years, gaining science writing experience at The Scripps Research Institute and Ionis Pharmaceuticals. As a Ph.D. molecular biologist, she is passionate about advancing the public’s understanding of science. In addition to being a self-proclaimed “science geek,” she is regularly asked to speak at international scientific meetings. When not teaching and writing the WEEKLY for Biotech Primer, Dr. Burke swims with her swim club and performs regularly on the improv circuit in San Diego.