Page 91 - Genetics_From_Genes_to_Genomes_6th_FULL_Part2

250 Chapter 7 Anatomy and Function of a Gene: Dissection Through Mutation

gene contains information that somehow encodes the struc- NH 2 –CHR–COOH (Fig. 7.28a). The –COOH component,
ture of an enzyme molecule. also known as carboxylic acid, is, as the name implies,
Although the analysis of the arginine pathway studied acidic; the –NH 2 component, also known as an amino
by Beadle and Tatum was straightforward, studies of bio- group, is basic. The R refers to side chains that distin-
chemical pathways are not always so easy to interpret. guish each of the amino acids (Fig. 7.28b). An R group
Some biochemical pathways are not linear progressions of can be as simple as a hydrogen atom (in the amino acid
stepwise reactions. For example, a branching pathway oc- glycine) or as complex as a benzene ring (in phenylala-
curs if different enzymes act on the same intermediate to nine). Some side chains are relatively neutral and nonre-
convert it into two different end products. If the cell re- active, others are acidic, and still others are basic.
quires both of these end products for growth, a mutation in In addition to the 20 common amino acids, two rare
a gene encoding any of the enzymes required to synthesize ones can be incorporated into proteins in specific cir-
the intermediate would make the cell dependent on supple- cumstances (Fig. 7.28c). A very few proteins (only 25 in
mentation with both end products. A second possibility is humans) are known to contain selenocysteine. Pyrroly-
that a cell might employ either of two independent, parallel sine is present only in the proteins of certain prokaryotic
pathways to synthesize a needed end product. In such a organisms.
case, a mutation in a gene encoding an enzyme in one of During protein synthesis, a cell’s protein-building
the pathways would be without effect. Only a cell with machinery links amino acids by constructing covalent
mutations affecting both pathways would display an aber- peptide bonds that join the –COOH group of one amino
rant phenotype. acid to the –NH 2 group of the next (Fig. 7.28d). A pair of
Even with nonlinear progressions such as these, care- amino acids connected in this fashion is a dipeptide; sev-
ful genetic analysis can reveal the nature of the biochemical eral amino acids linked together constitute an oligopep-
pathway on the basis of Beadle and Tatum’s insight that tide. The amino acid chains that make up proteins contain
genes specify proteins. hundreds to thousands of amino acids joined by peptide
bonds and are known as polypeptides. Proteins are thus
linear polymers of amino acids. Like the chains of nucleo-
tides in DNA, polypeptides have a chemical polarity. The
Genes Specify the Identity and Order end of a polypeptide synthesized first is called the N
of Amino Acids in Polypeptide Chains terminus because it contains a free amino group that is
Although the one gene, one enzyme hypothesis was a not connected to any other amino acid. The other end of
crucial advance in understanding how genes influence the polypeptide chain is the C terminus because it con-
phenotype, it is an oversimplification. Not all genes gov- tains a free carboxylic acid group.
ern the construction of enzymes active in biochemical
pathways. Enzymes are only one class of the molecules
known as proteins, and cells contain many other kinds of Mutations can alter amino acid sequences
proteins. Among the other types are proteins that provide
shape and rigidity to a cell, proteins that transport mole- Each protein is composed of a unique sequence of amino
cules in and out of cells, proteins that help fold DNA into acids. The chemical properties that enable structural
chromosomes, and proteins that act as hormonal messen- proteins to give a cell its shape, or allow enzymes to
gers. Genes direct the synthesis of all proteins, enzymes catalyze specific reactions, are a direct consequence of
and nonenzymes alike. Moreover, as we see next, genes the identity, number, and linear order of amino acids in
actually determine the construction of polypeptides, and the protein.
because some proteins are composed of more than one If genes specify proteins, then at least some muta-
type of polypeptide, more than one gene determines the tions could be changes in a gene that alter the normal
construction of such proteins. sequence of amino acids in the protein specified by that
gene. In the mid-1950s, Vernon Ingram began to estab-
lish what kinds of changes particular mutations cause in
the corresponding protein. Using techniques that had just
Proteins: Linear polymers of amino been developed for determining the sequence of amino
acids linked by peptide bonds acids in a protein, he compared the amino acid sequence
Proteins are polymers composed of building blocks known of the normal adult form of hemoglobin (HbA) with that
as amino acids. Cells use mainly 20 different amino acids of hemoglobin in the bloodstream of people homozygous
to synthesize the proteins they need. All of these amino acids for the mutation that causes sickle-cell anemia (HbS).
have certain basic features, encapsulated by the formula Remarkably, he found only a single amino acid difference