Page 144 - Genetics_From_Genes_to_Genomes_6th_FULL_Part2

8.5 The Effects of Mutations on Gene Expression and Function 303

A striking example of a neomorphic allele that ex­ Consider, for example, a gene encoding a polypeptide
Ns
presses a normal protein ectopically is the Antp mutant that associates with three other identical polypeptides in a
allele of the Drosophila gene Antennapedia. Flies that are four­subunit enzyme. All four subunits are products of the
Ns
Antp /Antp heterozygotes have legs on their heads in same gene. If a dominant mutant allele D directs the synthesis
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place of antennae (Fig. 8.32a). The Antp gene encodes a of a poison subunit whose presence in the multimer—even as
protein that promotes leg development; accordingly, the one subunit out of four—abolishes enzyme function, then
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wild­type allele Antp is transcribed in tissues that will be­ active tetramers composed solely of functional wild­type d
come the fly’s legs. A mutation within the transcriptional subunits are only 1/16 of all tetramers produced (Fig. 8.33a).
control region of the gene instead causes the Antp allele to As a result, total enzyme activity in D/d heterozygotes is far
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Ns
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express normal protein in tissues destined to become the less than that seen in wild­type d /d homozygotes. The
antennae (Fig. 8.32b). Antp is dominant because the Kinky allele of the Axin gene in mice, which results in a mal­
Ns
Antp allele does not prevent the ectopic expression of Antp formed (kinky) tail, is an example of a dominant negative
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protein in the cells normally destined to become antennae. mutation with such a mechanism of action (Fig. 8.33b).
Antimorphic alleles Figure 8.33 Why some dominant mutant alleles are
Some dominant mutant alleles of genes encode proteins that antimorphic. (a) With proteins composed of four subunits encoded
by a single gene, a dominant negative mutation may inactivate 15 out
not only fail to provide the activity of the wild­type protein, but of every 16 multimers. (b) The Kinky allele of the mouse gene Axin
also prevent the normal protein from functioning. Such alleles (Axin Kinky ) is a dominant negative mutation that causes a kink in the
are called dominant-negative, or antimorphic, alleles. tail. The Axin protein is a subunit of a protein complex; the protein
encoded by Axin Kinky prevents the complex from working.
b: © Tom Vasicek
Figure 8.32 Neomorphic alleles can express a normal (a) The antimorphic allele D encodes a mutant poison subunit
Ns
protein ectopically. (a) A neomorphic dominant mutation (Antp )
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in the fly Antennapedia gene produces flies with two legs growing d / d + D /d +
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out of the head (right); a normal fly head is shown at left. (b) Antp
has a mutant transcriptional control region that results in ectopic
expression of the leg-determining Antp protein in cells normally
destined to become antennae.
a.1: © Eye of Science/Science Source; a.2: © Juergen Berger/Science Source Functional
Ns
(a) The dominant neomorphic allele Antp causes enyzme
antenna-to-leg transformation
Normal
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Ns
Antp /Antp + Antp /Antp + subunit
encoded
by d +
allele
Mutant
subunit
encoded
by D
allele Functional
enyzme
(b) Phenotypic e ect of the poison subunit encoded by the
antimorphic allele Axin Kinky
Ns
(b) Antp expresses Antp protein ectopically
Axin Kinky /Axin +
Leg
enhancer
Antp +
mRNA in leg
precursor cells
Antp Protein in leg
precursor cells
Antenna
enhancer
Antp Ns
mRNA in antenna
precursor cells
Antp Protein in antenna
precursor cells