Hartl, Jones - Genetics. Principlers and analysis - 1998, страница 12

In the process on the left, the top strand is the template present in the parental molecule, and thebottom strand is the newly synthesized partner. InPage 11Figure 1.6Replication of DNA. (A) Each of the parental strands serves as a template for the production of a complementarydaughter strand, which grows in length by the successive addition of single nucleotides.(B) Replication in along DNA duplex as originally proposed by Watson and Crick.

As the parental strands separate, each parentalstrand serves as a template for the formation of a new daughter strand by means of A—T and G—C base pairing.the process on the right, the bottom strand is the template from the parental molecule, and the top strand is thenewly synthesized partner. How the process of replication occurs in a long duplex molecule is shown in Figure1.6B. The separation of the parental strands and the synthesis of the daughter strands take place simultaneously indifferent parts of the molecule.

In each successive region along the parental duplex, as the parental strands comeapart, each of the separated parental strand serves as a template for the synthesis of a new daughter strand.Page 121.4—Genes and ProteinsBy the beginning of the twentieth century, it had already become clear that proteins were responsible for most ofthe metabolic activities of cells. Proteins were known to be essential for the breakdown of organic molecules togenerate the chemical energy needed for cellular activities. They were also known to be required for the assemblyof small molecules into more complex molecules and cellular structures. In 1878, the term enzyme was introducedto refer to the biological catalysts that accelerate biochemical reactions in cells.

By 1900, owing largely to thegenius of the German biochemist Emil Fischer, enzymes had been shown to be proteins. Other proteins are keycomponents of cells; for example, structural proteins give the cell form and mobility, other proteins form pores inthe cell membrane and control the traffic of small molecules into and out of the cell, and still other proteinsregulate cellular activities in response to molecular signals from the external environment or from other cells.In 1908, the British physician Archibald Garrod had an important insight into the relationship between enzymesand disease:Any hereditary disease in which cellular metabolism is abnormal results from an inherited defect in an enzyme.Such hereditary diseases became known as inborn errors of metabolism, a term still in use today.

Although thefull implications of Garrod's suggestion could not be explored experimentally until many years afterward, thecoupling of the concepts of inheritance (gene) with enzyme (protein) was a brilliant simplification of the problemof biochemical genetics because it put the emphasis on the question "How do genes control the structure ofproteins?" How biologists pursued this question is summarized in the following sections.Transcription of DNA Makes RNAWatson and Crick were quite right in suggesting that the genetic information in DNA is contained in the sequenceof bases; it is encoded in a manner analogous to letters (the bases) printed on a strip of paper. However, learningthe details of the genetic code and the manner in which it is deciphered took about 20 years of additional work.

Thelong series of investigations showed that in a region of DNA that directs the synthesis of a protein, the genetic codefor the protein is contained in a DNA strand. The coded genetic information in this strand is decoded in a linearorder in which each successive "word" in the DNA strand specifies the next chemical subunit to be added to theprotein as it is being made. The protein subunits are called amino acids. Each "word" in the genetic code consistsof three adjacent bases.For example, the base sequence ATG in a DNA strand specifies the amino acid methionine (Met), TTT specifiesphenylalanine (Phe), GGA specifies glycine (Gly), and GTG specifies valine (Val). How the genetic information istransferred from the base sequence of a DNA strand into the amino acid sequence of the corresponding protein isshown in Figure 1.7.

This scheme, in which DNA codes for RNA and RNA codes for proteins, is known as thecentral dogma of molecular genetics. (The term dogma means a set of beliefs. The term dates from the time whenthe idea was first advanced as a theory; since then, the "dogma" has been confirmed experimentally, but the termpersists.)The main concept in the central dogma is that DNA does not code for protein directly but acts through anintermediary molecule called ribonucleic acid (RNA). The structure of RNA is similar, but not identical, to that ofDNA. The sugar is ribose rather than deoxyribose.

RNA is usually single-stranded (not a duplex), and RNAcontains a base, uracil (U), that takes the place of thymine (T) in DNA (Chapter 5). In the synthesis of proteins,there are actually three types of RNA that participate and that play different roles:• A messenger RNA (mRNA), which carries the genetic information from DNA and is used as a template forprotein synthesis.• The ribosomal RNA (rRNA), which is a major constituent of the cellular parti-Page 13Figure 1.7The "central dogma" of molecular genetics: DNA codes for RNA,and RNA codes for protein. The DNAand the RNARNA step is transcriptionprotein step is translation.cles called ribosomes on which protein synthesis actually takes place.• A set of transfer RNA (tRNA) molecules, each of which incorporates a particular amino acid subunit into thegrowing protein when it recognizes a specific group of three adjacent bases in the mRNA.Why on Earth should a process as functionally simple as DNA coding for protein have the additional complexity ofRNA intermediaries? Certain biochemical features of RNA suggest a hypothesis: that RNA played a central role inthe earliest forms of life and that it became locked into the processes of information transfer and protein synthesis.So it remains today: The participation of RNA in protein synthesis is a relic of the earliest stages of evolution—a"molecular fossil." The hypothesis that the first forms of life used RNA both for carrying information (in the basesequence) and as catalysts (accelerating chemical reactions) is supported by a variety of observations.

Twoexamples: (1) DNA replication requires an RNA molecule in order to get started (Chapter 5), and (2) some RNAmolecules act to catalyze biochemical reactions important in protein synthesis (Chapter 10). In the later evolutionof the early life forms, additional complexity could have been added. The function of information storage andreplication could have been transferred from RNA to DNA, and the function of RNA catalysis in metabolism couldhave been transferred from RNA to protein by the evolution of RNA-directed protein synthesis.The manner in which genetic information is transferred from DNA to RNA is straightforward (Figure 1.8).

TheDNA opens up, and one of the strands is used as a template for the synthesis of a complementary strand of RNA.(How the template strand is chosen is discussed in Chapter 10.) The process of making an RNA strand from a DNAtemplate is transcription, and the RNA molecule that is made is the transcript. The base sequence in the RNA iscomplementary (in the Watson-Crick pairing sense) to that in the DNA template, except that U (which pairs withA) is present in the RNA in place of T. The base-pairing rules between DNA and RNA are summarized in Figure1.9. Like DNA, an RNA strand also has a polarity, exhibiting a 5' end and a 3' end determined by the orientation ofthe nucleotides.

The 5' end of the RNA transcript is synthesized first and, in the RNA—DNA duplex formed intranscription, the polarity of the RNA strand is opposite to that of the DNA strand.Page 14Figure 1.8Transcription is the production of an RNA strand that is complementaryin base sequence to a DNA strand. In this example, the DNA strand at thebottom left is being transcribed into a strand of RNA. Note that in an RNAmolecule, the base U (uracil) plays the role of T (thymine) in that it pairswith A (adenine).

Each A—U pair is marked.Figure 1.9Pairing between bases in DNA and in RNA. The DNA bases A, T, G, and Cpair with the RNA bases U, A, C, and G, respectively.Translation of RNA Makes ProteinThe synthesis of a protein under the direction of an mRNA molecule is translation. Although the sequence ofmRNA bases codes for the sequence of amino acids, the molecules that actually do the "translation" are the tRNAmolecules. The mRNA molecule is translated in groups of three bases called codons.

For each codon in themRNA, there is a tRNA molecule that contains a complementary group of three adjacent bases that can pair withthose in the codon. At each step in protein synthesis, when the proper tRNA with an attached amino acid comesinto line along the mRNA, the incomplete protein chain is attached to the amino acid on the tRNA, increasing thelength of the protein chain by one amino acid. When the next tRNA comes into line, the protein chain is detachedfrom the previous tRNA and attached to the amino acid of the next in line, again increasing the length of theprotein chain by one amino acid. A protein is therefore synthesized in a stepwise manner, one amino acid at a time.By way of analogy, the process of protein synthesis by the addition of consecutive amino acids is like theconstruction of a chain of pop-together plastic beads by the addition of consecutive beads.The role of tRNA in translation is illustrated in Figure 1.10 and can be described as follows:The mRNA is read codon by codon.