are joined in a long, single strand that pairs with a second, complementary strand. This second strand contains a mirror image of the DNA bases found in the first strand. Throughout the length of this long, doubled molecule, all As in one strand pair with Ts in the other strand, and all Gs in one strand pair with Cs in the other strand. The combination is referred to as a “base pair.” The two strands of the DNA molecule wind around each other, with the pitch determined by the angle of the molecular bonds between each base; hence, DNA is referred to as a “double helix.”
DNA replication
The two-stranded structure of DNA serves two functions. Firstly, the second strand is a mirror image of the first strand, and any damage to one strand can be repaired precisely using the alternate strand as a template. DNA repair enzymes constantly monitor DNA sequences and repair damage. Second, the two complementary DNA strands provide a remarkably simple system for the replication of the DNA molecule. The two stands separate from one another and enzymes, called DNA polymerases, create complementary strands using the original strands as templates. At the end of the process, there are two chemically identical DNA molecules.
The central dogma of genetics (DNA ≥ RNA ≥ protein)
One of the major roles of DNA is to encode proteins. This is important because the protein functions are determined by the composition and order of amino acids in the polypeptide chain. The process is basically the following: DNA contains a code within its sequence which is “transcribed” into another information molecule called ribonucleic acid (RNA). The process of transferring the information from DNA to RNA is called “transcription.” Transcription is sometimes referred to as “gene expression.” RNA is similar to DNA except that: (i) it is a single-stranded copy of one of the DNA strands; (ii) its structural backbone contains the sugar “ribose” rather than “deoxyribose”; and (iii) it substitutes the nucleic acid uracil (U) for thymidine (T) wherever thymidine would have occurred based on the sequence of the DNA molecule. In transcription, one of the DNA strands is used as a template to make a complementary RNA strand such that a sequence “ATTCGAAGG” of DNA, for example, is transcribed to an RNA strand with the sequence “UAAGCUUCC.” The transcribed RNA strand is only a section of the DNA representing the gene of interest. It is therefore short and moves easily through the cell to engage the protein-manufacturing complex called a ribosome. Ribosomes travel down the RNA molecule, reading each set of three nucleotides and adding 1 of 20 amino acids according to the instructions from the genetic code. The term “translation” denotes the process of reading the RNA molecule and producing the protein.
Amino acids are small molecules which can be joined in series to create longer molecules called polypeptides, more commonly referred to as proteins. Proteins are the linear arrangement of tens to thousands of amino acids from among the basic set of 20 different amino acids (Table 4.1). The differences between amino acids reside in the side chains attached to the amino and carboxyl core of the molecule. Some of the side chains repel water, some attract water, some are basic or acidic, others have the capacity to form attachments with other amino acids (disulfide bonds). Altogether, the combination of amino acids and their side chains causes the folding of the linear peptide and provides clefts, pockets, and receptor sites that make the protein biologically active as a structure or an enzyme. Examples of proteins include hemoglobin, immunoglobulin, and the diverse molecules making up muscle fibers, as well as the liver enzymes which detoxify blood and blood clotting enzymes which heal wounds. Mammalian genomes contain over 20,000 genes for proteins (Chapter 6).
Table 4.1. The genetic code based on RNA sequences read by the ribosome. The triplet codes for each of the 20 amino acids found in proteins are presented, as well as the codon signals that start and stop protein synthesis.
Genetic code
DNA is an information molecule. It contains all the information necessary to transform a single cell, specifically a fertilized egg, into a complex, multicellular individual. Scientists were initially surprised that a molecule with only four basic units—A, T, G, and C—could deliver sufficient information. However, the information was found to be contained in the precise order of bases along the molecule. Each DNA molecule is millions of base pairs long with any one of the four bases possible at each position. The number of possible, random permutations of base order for chromosomes exceeds the number of animals that have ever existed! However, this is an information molecule and the order of bases is not random.
The function of a protein is based on the precise number and order of amino acids in its composition. The DNA sequence specifies the order and composition of amino acids in a protein based on a three-nucleotide code. Each group of three nucleotides that specify a particular amino acid is called a “codon.” As ribosomes move down RNA molecules, they begin at a precise point, determined by multiple factors (including the start codon, AUG), read the DNA sequence as a set of three nucleotides, then jump to the next set of three. Codons do not overlap. Each set of three is read in sequence. The triplet codes of RNA bases for amino acids are shown in Table 4.1.
Because four possible bases are used to create codons of three bases, there are 64 possible codons (43). As shown in Table 4.1, the 64 codons are used to signal the 20 amino acids (listed in columns 1 and 3) as well as to provide a signal to start (START) or stop (STOP) protein production. As there are 64 possibilities for 20 amino acids and two signals (start and stop), most amino acids can be encoded by more than one codon. This is referred to as “redundancy of the genetic code.” For example, alanine, in the top left corner of Table 4.1, is encoded by four different codons. Only two amino acids, methionine and tryptophan, have a single codon. The amino acids with the largest number of possible codons are arginine, leucine, and serine with six each.
Identification of genetic variation at the DNA level for horses
One of the most common types of genetic variation detectable at the DNA level is called a single nucleotide polymorphism (SNP and pronounced “SNiP”). Fig. 4.1 illustrates a SNP. Recall that DNA is made up of billions of bases called nucleotides. When just one of them is mutated it may change from A to C, or G to T, or C to A, etc. When that happens, the DNA can exist in two forms at that site—essentially, it becomes polymorphic (derived from the Greek for “many forms”).
Fig. 4.1. Comparison of base sequences of DNA strands illustrating a single nucleotide polymorphism (SNP). A hypothetical sequence is shown for five horses. The bold letter denotes the presence of a SNP, a site at which two horses have a T and three horses have a C.
Other types of variation include rearrangements of DNA, such as inversions, duplications, and translocations from one site to another, as well as insertions and deletions of DNA, ranging from single bases to large sections with tens of thousands of bases.
Mutations and variants affecting proteins
Where does genetic variation come from? Sometimes DNA is altered. We know that some chemicals, UV light, and radiation can alter DNA. In addition, random errors may occur
