Learning About Your Genes

The following sections are included:

• Dedication
• Contents
• About the Author
• Acknowledgments

While once chatting with one of my grandchildren I was faced with a probing question. “Grandpa” he asked, “where did you come from? Not just your father and mother and your grandparents, but before them?” Surprised, but gratified that one of my grandchildren was interested in his genealogy I informed him that while I had no immediate answer to his question, I’d try my best to find one…

The first documentation of the existence of genes came from studies carried out about 160 years ago by Gregor Johann Mendel, a monk at St. Thomas Abbey in the city of Brono, Czechoslovakia. Mendel was born in I822 with the Christian name Johann. The more familiar name Gregor was added when he joined St. Thomas Monastery years later.

Most studies of biology ultimately seek an understanding of the biology of humans — of you and me! However, many biological experiments are technically challenging and frequently involve procedures that result in death of the organism under study. For these and other cogent reasons the use of human subjects for many biological studies is forbidden by most if not all agencies that provide financial support for biological research. Consequently, molecular biologists, biochemists, geneticists and other members of the biological research community have for many years explored the biology of organisms that are inexpensive to maintain and house, multiply quickly, and are easy to handle and store in the laboratory. Organisms ranging from simple bacteria to flies to rodents and even primates such as monkeys have over the years served as the mainstay of biological research and are referred to as model organisms. Bacteria are frequently used model organisms for the study of genes, particularly a bacterium called Escherichia coli (E. coli for short), a generally harmless organism present in the intestines of many animals, including humans.

In order to understand genes and their role in instructing cells to synthesize (manufacture) proteins, it’s important to understand the structure of DNA, a structure elucidated in 1953 by an American scientist James (known to the scientific world as Jim) Watson and an English colleague Francis Crick; legendary names you may be familiar with, who were awarded Nobel Prizes in 1962. The elucidation of the structure of DNA by Watson and Crick is considered by many as one of the most momentous and far-reaching discoveries in biology.

The precise number of genes in the human genome (a word that describes your entire complement of genes) is not known since they are difficult to count. Presently the number of known human genes that carry an instructional code for making proteins is believed to be somewhere around 20,000. Other genes are known to regulate the genes that specify proteins. But the total number of genes known to instruct cells to make proteins, plus those that are known to regulate this function only occupy about 2% of the DNA in a cell. The remaining stretches of DNA in our cells have no known function at this time! Clearly there is still much to learn about DNA.

As already mentioned, the frequency and order of the bases A, T, C and G in the DNA of our genes embodies a code, referred to as the genetic code; a code that instructs the synthesis (manufacture) of the multiple proteins in the cells of living organisms. Proteins are made up of multiple small chemical units called amino acids of which there are 20. Each protein consists of different amino acids linked in different orders in chains called polypeptides, in much the same way that DNA consists of chains of four bases in different orders and lengths. Proteins may be comprised of a single polypeptide or multiple polypeptide chains. Once a polypeptide is completed it folds in a specific manner that generates a fully formed and functional protein (Fig. 6-1).

You will presumably be surprised to learn that your DNA does not consist of a long uninterrupted sequence of bases that exclusively code for the synthesis of chains of amino acids that become proteins. Non-coding regions of DNA called introns interrupt the coding regions, which are called exons. During transcription to generate messenger RNA (mRNA) the entire gene is first transcribed to pre-mRNA, which includes both exons and introns. During a process called RNA splicing, introns are removed from the genome and the exons are joined to form contiguous coding sequences. The mature mRNA is then available for translation.

You might reasonably believe that the DNA in your cells is well protected in its cocoon of chromosomes, snuggly buried in the nuclei of your cells. Regrettably, such is not the case. DNA is a highly reactive biological compound that sustains various types of damage and alterations by interacting with chemicals that are generated during normal metabolic processes or by interaction with man-made chemicals that enter our bodies. Some of the chemicals that arise during metabolic processes are referred to as Reactive Oxygen Species (ROS). ROS are the products of normal oxygen-consuming metabolic process in the body that are highly reactive with DNA. You may be shocked to learn that in humans, naturally occurring oxidative DNA damage has been calculated to occur at least 10,000 times per cell per day. That’s a lot of DNA damage!

As you now hopefully comprehend, when synthesizing new DNA the enzyme DNA polymerase “knows” that the base A must always be placed opposite T, and C must be placed opposite G. As mentioned in the previous chapter, DNA polymerase (that like all enzymes is not perfect in its function) sometimes incorporates an incorrect nucleotide during DNA synthesis — thankfully very rarely. For example, instead of the base A being incorporated opposite T in a growing chain of DNA, the incorrect base C or G or even another T may be added to the growing chain. Incorrect or unrepaired damaged bases in genes can generate mutations that may interfere with the normal function of affected genes, sometimes leading to serious diseases — such as cancer.

Recent decades have witnessed the emergence of a number of technologies that have facilitated deeper insights about genes and DNA.

Early in this book, I informed you that the great majority of the DNA in your cells is found in chromosomes in the nuclei of cells. The reason that I did not offer that all the DNA in your cells is located in chromosomes stems from the fact that 57 years ago several research teams independently discovered that tiny structures in the cytoplasm of our cells called mitochondria (Fig. 3-2) also contain DNA (mtDNA). A huge surprise! Nuclear and mitochondrial DNA are thought to be of separate evolutionary origin.

Svante Pääbo, a Swedish biologist and a recognized authority on evolutionary genetics, is one of the founders of the discipline of paleogentics, a discipline that deploys the methods of genetics and genomics to study early humans and other ancient populations. Pääbo has been director of the Department of Genetics at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany since 1997. In 2014 he published a book entitled Neanderthal Man: In Search of Lost Genomes, in which he relates the history of the research efforts in his laboratory.

When and how did DNA with its large complement of genes arise as the bearers of life? This question has been around for a long time, but there is no definitive answer. The succeeding paragraphs are intended to give the reader a sense of the complexity of this question and some of the thoughts and suggestions that have emerged…

The sequence of the bases A, T, C and G in a stretch of DNA can be determined using techniques that are now standard in research laboratories in most if not all academic institutions. However, such laboratories do not have the capacity to handle sequencing the genome of organisms such as humans, which is estimated to contain about 25,000 genes as well as many more bases that are not part of any gene.

I hope that you enjoyed reading this book and did not experience too much difficulty understanding most, if not all of its content; and more importantly, that you learned something about your genes and how they function.

The following sections are included:

• Glossary
• Index