Microbiology and Immunology

Genetic code WORLD OF MICROBIOLOGY AND IMMUNOLOGY

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no longer the nebulous units described by Mendel purely in

terms of their visible expression (phenotypic expression). It is

now possible to understand their molecular structure and func-

tion in considerable detail. The biological role of genes is to

carry, encode, or control information on the composition of

proteins. The proteins, together with their timing of expression

and amount of production are possibly the most important

determinants of the structure and physiology of organisms.

Each structural gene is responsible for one specific protein or

part of a protein and codes for a single polypeptide chain via

messenger RNA (mRNA). Some genes code specifically for

transfer RNA (tRNA) or ribosomal RNA (rRNA) and some

are merely sequences, which are recognized by regulatory pro-

teins. The latter are termed regulator genes. In higher organ-

isms, or eukaryotes, genes are organized in such a way that at

one end, there is a region to which various regulatory proteins

can bind, for example RNA polymerase during transcription,

and at the opposite end, there are sequences encoding the ter-

mination of transcription. In between lies the protein encoding

sequence. In the genes of many eukaryotes this sequence may

be interrupted by intervening non-coding sequence segments

called introns, which can range in number from one to many.

Transcription of eukaryotic DNA produces pre–mRNA con-

taining complementary sequences of both introns and the

information carrying sections of the gene called exons. The

pre–mRNA then undergoes post–transcriptional modification

or processing in which the introns are excised and exons are

spliced together, leaving the complete coding transcript of

connected exons ready to code directly for the protein. When

the central dogma of genetics was first established, a “one

gene–one enzyme” hypothesis was proposed, but today it is

more accurate to restate this as a one to one correspondence

between a gene and the polypeptide for which it codes. This is

because a number of proteins are now known to be constituted

of multiple polypeptide subunits coded for by different genes.

See alsoBacterial artificial chromosome (BAC); Chromo-

somes, eukaryotic; Chromosomes, prokaryotic; DNA

(Deoxyribonucleic acid); Evolution and evolutionary mecha-

nisms; Gene amplification; Genetic code; Genetic mapping;

Genotype and phenotype; Immunogenetics; Microbial genet-

ics; Molecular biology, central dogma of; Molecular biology

and molecular genetics

GENE CHIPS•seeDNACHIPS AND MICROARRAYS

GENETIC CAUSES OF IMMUNODEFICIENCY

• seeIMMUNODEFICIENCY DISEASE SYNDROMES

GGenetic codeENETIC CODE

The genetic code is the set of correspondences between the

nucleotide sequences of nucleic acids such as DNA (deoxyri-

bonucleic acid), and the amino acid sequences of polypep-

tides. These correspondences enable the information encoded

in the chemical components of the DNA to be transferred to

the ribonucleic acidmessenger (mRNA), and then to be used

to establish the correct sequence of amino acids in the

polypeptide. The elements of the encoding system, the

nucleotides, differ by only four different bases. These are

known as adenine (A), guanine, (G), thymine (T) and cytosine

(C), in DNA or uracil (U) in RNA. Thus, RNA contains U in

the place of C and the nucleotide sequence of DNA acts as a

template for the synthesis of a complementary sequence of

RNA, a process known as transcription. For historical reasons,

the term genetic code in fact refers specifically to the sequence

of nucleotides in mRNA, although today it is sometimes used

interchangeably with the coded information in DNA.

Proteins found in nature consist of 20 naturally occur-

ring amino acids. One important question is, how can four

nucleotides code for 20 amino acids? This question was raised

by scientists in the 1950s soon after the discovery that the

DNA comprised the hereditary material of living organisms. It

was reasoned that if a single nucleotide coded for one amino

acid, then only four amino acids could be provided for.

Alternatively, if two nucleotides specified one amino acid,

then there could be a maximum number of 16 (4^2 ) possible

arrangements. If, however, three nucleotides coded for one

amino acid, then there would be 64 (4^3 ) possible permutations,

more than enough to account for all the 20 naturally occurring

amino acids. The latter suggestion was proposed by the

Russian born physicist, George Gamow (1904–1968) and was

later proved correct. It is now well known that every amino

acid is coded by at least one nucleotide triplet or codon, and

that some triplet combinations function as instructions for the

termination or initiation of translation. Three combinations in

tRNA, UAA, UGA and UAG, are termination codons, while

AUG is a translation start codon.

The genetic code was solved between 1961 and 1963.

The American scientist Marshall Nirenberg (1927– ), working

with his colleague Heinrich Matthaei, made the first break-

through when they discovered how to make synthetic mRNA.

They found that if the nucleotides of RNA carrying the four

bases A, G, C and U, were mixed in the presence of the enzyme

polynucleotide phosphorylase, a single stranded RNA was

formed in the reaction, with the nucleotides being incorporated

at random. This offered the possibility of creating specific

mRNA sequences and then seeing which amino acids they

would specify. The first synthetic mRNA polymer obtained

contained only uracil (U) and when mixed in vitrowith the pro-

tein synthesizing machinery of Escherichia coliit produced a

polyphenylalanine—a string of phenylalanine. From this it was

concluded that the triplet UUU coded for phenylalanine.

Similarly, a pure cytosine (C) RNA polymer produced only the

amino acid proline so the corresponding codon for cytosine had

to be CCC. This type of analysis was refined when nucleotides

were mixed in different proportions in the synthetic mRNA and

a statistical analysis was used to determine the amino acids

produced. It was quickly found that a particular amino acid

could be specified by more than one codon. Thus, the amino

acid serine could be produced from any one of the combina-

tions UCU, UCC, UCA, or UCG. In this way the genetic code

is said to be degenerate, meaning that each of the 64 possible

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