Page 83 - Genetics_From_Genes_to_Genomes_6th_FULL_Part1

3.3 Extensions to Mendel for Multifactorial Inheritance 75

Figure 3.29 Genes E, A, and K control the switch between light and dark pigment synthesis in melanocytes. MCR1
is specified by gene E. (a) At left, Beta-defensin (specified by gene K) out-competes ASIP for MC1R binding and switches MC1R on;
melanocytes produce eumelanin (dark pigment). At right, melanocytes produce pheomelanin (light pigment) when ASIP (specified by gene
A) out-competes Beta-defensin for MC1R binding. When bound by ASIP, MCR1 does not signal. (b) At left, the version of Beta-defensin
b
made by the Labrador’s K alleles always binds MC1R because it out-competes the version of ASIP made by their a alleles. As a result,
eumelanin is synthesized and the dog is either black or chocolate (depending on its alleles of gene B). At right, the melanocytes of yellow
Labrador retrievers lack MC1R (their ee alleles are nonfunctional), and pheomelanin is made by default.
(a) The switch between eumelanin and pheomelanin in melanocytes
Eumelanin synthesis Pheomelanin synthesis

A protein A protein
MC1R Pheomelanin MC1R Pheomelanin
ASIP (E protein) ASIP (E protein)

-Defensin ASIP

Switch ON Switch OFF
-
-Defensin Defensin
Eumelanin Eumelanin
K protein K protein

(b) Control of the eumelanin/pheomelanin switch in Labrador retrievers
Black or chocolate Yellow
Inactive Inactive
A protein A protein
MC1R Pheomelanin Pheomelanin
(E protein)
a a

K b

Switch ON Switch OFF
K b K b
Eumelanin Eumelanin
K protein K protein

b b
b b
aa K K E- aa K K ee

w
lot of pheomelanin in addition to eumelanin. The a allele muzzle are most sensitive to the effects of this increased
(like the A allele in mice) gives the dogs an overall gray eumelanin.
(agouti) color. In an agouti dog (or mouse), the hairs are Three alleles of the K gene determine whether or not
mainly black with a single yellow stripe. In both species, the A gene markings are visible, and we consider two of
the a allele results in lighter hair on the belly and solid dark them here. The K allele present in Labradors specifies a
b
t
hairs on the back. version of Beta-defensin that is made in all melanocytes
t
w
The ee genotype is epistatic to A , a , and a because and can out-compete any of the different ASIP proteins
Y
these A gene phenotypes require the hair to have some dark made by gene A alleles. Thus in a K – dog, eumelanin is
b
pigment. Some dogs breeds have an allele of gene E called made all of the time, regardless of whether or not ASIP is
E that is dominant to both E and e and directs the forma- present. If an E– dog is also K – (like black or chocolate
b
m
m
tion of a dark mask (Fig. 3.30). The E allele specifies Labrador retrievers), the dog is solidly dark regardless of
a version of MC1R thought to cause more eumelanin its A gene alleles: K is epistatic to all alleles of gene A. In
b
y
production than normal, and the melanocytes around the contrast, the version of Beta-defensin made by the k allele