Page 96 - Genetics_From_Genes_to_Genomes_6th_FULL_Part2

7.6 A Comprehensive Example: Mutations That Affect Vision 255

contrast, more than one kind of polypeptide makes up the site. Some kinds of amino acid substitutions, such as re-
protein (Fig. 7.31b). The different polypeptides in these placement of an amino acid having a basic side chain with
multimers are specified by different genes. an amino acid having an acidic side chain, would be more
Alterations in just one kind of subunit, caused by a likely to compromise protein function than would substitu-
mutation in a single gene, can affect the function of a mul- tions that retain the chemical characteristics of the original
timer. The adult hemoglobin molecule, for example, con- amino acid.
sists of two α and two β subunits, with each type of subunit Some mutations do not affect the amino acid composi-
determined by a different gene—one for the α chain and tion of a protein but still generate an abnormal phenotype.
one for the β chain. A mutation in the Hbβ gene resulting in As will be discussed in Chapter 8, such mutations change
an amino acid switch at position 6 in the β chain causes the amount of normal polypeptide produced by disrupting
sickle-cell anemia. the biochemical processes responsible for decoding a gene
Similarly, if several multimeric proteins share a com- into a polypeptide.
mon subunit, a single mutation in the gene encoding that
subunit may affect all the proteins simultaneously. An
example is an X-linked mutation in mice and humans that essential concepts
incapacitates several different proteins all known as
interleukin (IL) receptors. Because all of these receptors • Most genes specify the linear sequence of amino acids
are essential to the normal function of immune system in a polypeptide; this sequence determines the
cells that fight infection and generate immunity, this one polypeptide’s three-dimensional structure and thus its
mutation causes the life-threatening condition known as function.
X-linked severe combined immune deficiency (XSCID; • A missense mutation changes the identity of a single
Fig. 7.31c). amino acid in a polypeptide.
The polypeptides of complex proteins can assemble • Multimeric proteins include two or more polypeptides
into extremely large structures capable of changing with (subunits). If these subunits are different, they must be
the needs of the cell. For example, the microtubules that encoded by different genes.
make up the spindle during mitosis are gigantic assem-
blages of mainly two polypeptides: α-tubulin and β-tubulin
(Fig. 7.31d). The cell can organize these subunits into very
long hollow tubes that grow or shrink as needed at different
stages of the cell cycle. 7.6 A Comprehensive Example:
Mutations That Affect Vision
One gene, one polypeptide
Because more than one gene governs the production of learning objectives
some multimeric proteins and because not all proteins are
enzymes, the one gene, one enzyme hypothesis is not broad 1. Describe the functions of the four photoreceptor
enough to define gene function. A more accurate statement proteins in human vision.
is one gene, one polypeptide: Each gene governs the con- 2. Outline how the genes encoding the photoreceptors
struction of a particular polypeptide. As you will see in evolved through duplication and divergence of an
Chapter 8, even this reformulation does not encompass the ancestral gene.
function of all genes, as some genes in all organisms do not 3. Explain how mutations in the photoreceptor genes
determine the construction of proteins; instead, they spec- result in different vision defects.
ify RNAs that are not translated into polypeptides.
Knowledge about the connection between genes and
polypeptides enabled geneticists to analyze how different Researchers first described anomalies of color perception
mutations in a single gene can produce different pheno- in humans close to 200 years ago. Since that time, they
types. If each amino acid has a specific effect on the three- have discovered a large number of mutations that modify
dimensional structure of a protein, then changing amino human vision. By examining the phenotype associated
acids at different positions in a polypeptide chain can alter with each mutation and then looking directly at the DNA
protein function in different ways. For example, most en- alterations inherited with the mutation, they have learned a
zymes have an active site that carries out the enzymatic great deal about the genes influencing human visual per-
task, while other parts of the protein support the shape and ception and the function of the proteins they specify.
position of that site. Mutations that change the identity of Using human subjects for vision studies has several
amino acids at the active site may have more serious conse- advantages. First, people can recognize and describe varia-
quences than those affecting amino acids outside the active tions in the way they see, from trivial differences in what