Cell Biology. Stephen R. Bolsover
biology is “DNA makes RNA makes protein.” That central concept defines the structure of this section of the book, which moves from DNA through RNA to the synthesis of proteins. Single‐celled organisms change their behavior by altering the spectrum of RNAs and proteins that they make, while the cells of an animal or plant differentiate into different cell types by selecting different RNAs and proteins to synthesize. We will therefore describe the control mechanisms that operate to allow selective synthesis and readout of RNA. We will describe the ribosome, the machine for making protein using the instructions on DNA, and then describe the many and varied structures and behaviors of proteins. Lastly, in Chapter 8, we will describe some of the techniques that have made molecular biology such a powerful technology for both manipulating and investigating cells and organisms.
Chapter 3: DNA Structure and the Genetic Code
Chapter 4: DNA as a Data Storage Medium
Chapter 5: Transcription and the Control of Gene Expression
Chapter 6: Manufacturing Protein
Chapter 7: Protein Structure
Chapter 8: Recombinant DNA Technology and Genetic Engineering
3 DNA STRUCTURE AND THE GENETIC CODE
Our genes are made of deoxyribonucleic acid (DNA). This remarkable molecule contains all of the information needed to make a cell and to pass on this information when a cell divides. This chapter describes the structure and properties of DNA molecules, the way in which our DNA is packaged into chromosomes, and how the information stored within DNA is retrieved via the genetic code.
Deoxyribonucleic acid is an extremely long polymer made from monomeric units called deoxyribonucleotides (dNTPs), which are often simply called nucleotides. Nucleotides are made up of three components: a base, a sugar, and a phosphate group. Figure 3.1 shows a deoxyribonucleotide, deoxyadenosine triphosphate, on the left. On the right is the corresponding ribonucleotide, adenosine triphosphate or ATP. As mentioned in Chapter 2, ATP is the cell's primary energy currency. As we will see in Chapter 5, ATP also plays a critical role as one of the four nucleotides in RNA, taking the place of the deoxyadenosine triphosphate in DNA. Note that deoxyribose, unlike ribose, has no hydroxyl (OH) group on its 2′ carbon.
Four bases are found in DNA; they are the two purines guanine (G) and adenine (A) and the two pyrimidines thymine (T) and cytosine (C) (Figure 3.2). The lines represent covalent bonds formed when atoms share electrons, each seeking the most stable structure.
The combined base and sugar is known as a nucleoside to distinguish it from the phosphorylated form, which is called a nucleotide. Four different nucleotides are used to make DNA. They are 2′‐deoxyguanosine‐5′‐triphosphate (dGTP), 2′‐deoxyadenosine‐5′‐triphosphate (dATP), 2′‐deoxythymidine‐5′‐triphosphate (dTTP), and 2′‐deoxycytidine‐5′‐triphosphate (dCTP).
DNA molecules are very large. The single chromosome of the bacterium Escherichia coli is made up of two strands of DNA that are hydrogen‐bonded together to form a single circular molecule comprising 9 million nucleotides. DNA molecules in eukaryotes are even larger: the DNA molecules in humans comprise on average 260 million nucleotides, and a cell has 46 of these massive molecules, each forming one chromosome. We inherit 23 chromosomes from each parent. Each set of 23 chromosomes encodes a complete copy of our genome and is made up of 6 × 109 nucleotides (or 3 × 109base pairs – see below).
Figure 3.3 illustrates the structure of the DNA chain. As nucleotides are added to the chain by the enzyme DNA polymerase (Chapter 4), they lose two phosphate groups. The last (the α phosphate) remains and forms a phosphodiester bond between successive deoxyribose residues. This bond is formed between the hydroxyl group on the 3′ carbon of the deoxyribose of the last nucleotide in the DNA chain and the α‐phosphate group attached to the 5′ carbon of the nucleotide that the polymerase will add to the chain. The linkage gives rise to the sugar‐phosphate backbone of a DNA molecule. A DNA chain has polarity because its two ends are different. In the first nucleotide in the chain, the 5′ carbon of the deoxyribose is phosphorylated but otherwise free. This is called the 5′ end of the DNA chain. At the other end is a deoxyribose with a free hydroxyl group on its 3′ carbon. This is the 3′ end.
IN DEPTH 3.1 WE HAVE A SECOND GENOME IN OUR CELLS
The set of 23 chromosomes that we inherit from each parent encodes a complete copy of our nuclear genome that resides in the nucleus of our cells. We have a second genome that resides in our mitochondria – the energy‐producing organelles inside our cells. Unlike our large nuclear genome, which is organized in linear chromosomes, our mitochondrial genome is circular and only 16 569 base pairs in length. The mitochondrial genome contains 37 genes but only 13 of these encode proteins. These proteins are all involved in mitochondrial energy production. While nuclear genomes are inherited from both parents, our mitochondrial genome is always inherited maternally. This has allowed a prediction of “mitochondrial Eve,” the most recent female ancestor from whom all living humans descend in the matrilineal line, estimated to have lived between 165 000 and 190 000 years ago.