The structural gene for xanthine dehydrogenase [XDH
(EC.126.96.36.199)]; it is a homodimer with subunit molecular
weight estimated from its DNA sequence as 146,898 daltons
(Keith, Riley, Kreitman, Lewontin, Curtis, and Chambers, 1987,
Genetics 116: 67-73). Enzyme level responds to dose of ry+
alleles (Grell, 1962, Z. Indukt. Abstamm. Vererbungsl.
93: 371-77). XDH is a molybdenum hydroxylase and requires
the activity of cin+, lxd+, mal+ for normal activity, though
not for normal levels of CRM (Glassman, Shinoda, Duke, and
Collins, 1968, Ann. N. Y. Acad. Sci. 151: 263-73). CRM
(cross reacting material) contains bound molybdenum in the
presence of mal; however, enzyme activity inhibited (Andres
1976, Eur. J. Biochem. 62: 591-600). Homozygotes for null
alleles lack XDH activity (Forrest, Glassman, and Mitchell,
1956, Science 124: 725-26; Glassman and Mitchell, 1959,
Genetics 44: 153-62; Hubby and Forrest, 1960, Genetics
45: 211-24) and have reddish brown eyes; accumulate enzyme's
substrates, xanthine and 2-amino-4-hydroxypteridine as larvae
plus hypoxanthine in the adult; precursors collect as solid
granules in Malpighian tubules (Bonse, 1967, Z. Naturforsch.
22B: 1027-29); lack enzyme products uric acid and isoxanthopterin (Mitchell, Glassman, and Hadorn, 1959, Science
129: 268-69). Mutant homozygotes are also sensitive to
administration of purine to the medium (Glassman, 1965, Fed.
Proc. 24: 1243-51); survival on purine supplemented medium
can be used to select for rare ry+ recombinants (Chovnick,
Ballantyne, Baillie, and Holm, 1970, Genetics 66: 315-29) and
unequal crossovers producing tandem duplications (Gelbart and
Chovnick, 1979, Genetics 92: 849-59). Hypomorphic alleles
that have normal eye color are also sensitive to appropriate
levels of purine supplementation; furthermore, both wild types
and hypomorphs can be made to display mutant eye color by
administration of appropriate levels of the XDH inhibitor, HPP
(allopurinol) [4-hydroxypyrazolo-(3,4-d) pyrimidine] (Glassman, 1965, Fed. Proc. 24: 1243-51; Boni, DeLerma, and Parisi,
1967, Experientia 23: 186-87; McCarron and Chovnick, 1981,
Genetics 97: s70-71); in vitro and in vivo complementation
between mal and ry products was demonstrated by Glassman
(1952, Proc. Nat. Acad. Sci. USA 48: 1491-97; Glassman and
McLean, 1962, Proc. Nat. Acad. Sci. USA 48: 1712-18). Pigmentation is nonautonomous in ry eye disks transplanted into wild-type hosts (Hadorn and Schwink, 1956, Nature
177: 940-41). Enzyme levels climb from low levels in the
zygote to a peak at puparium formation; the level then falls
but increases again to a maximum a few days after eclosion
(Chovnick, McCarron, Hilliker, O'Donnell, Gelbart, and Clark,
1978, Cold Spring Harbor Symp. Quant. Biol. 42: 1011-21).
Enzyme derived from the paternal genome appears during gastrulation; activity at time zero is low in ry+ zygotes produced
by ry/+ females but undetectable in those produced by ry
females (Sayles, Browder, and Williamson, 1973, Dev. Biol.
33: 213-17). Enzyme activity present in larval and adult fat
bodies, larval and adult Malpighian tubules, and, in smaller
amounts, in various regions of the larval and adult gut
[Ursprung and Hadorn, 1961, Experientia 17: 230-31; Munz,
1964, Z. Indukt. Abstamm. Vererbungsl. 95: 195-210; Reaume,
Clark, and Chovnick, 1989, Genetics 123: 503-09; Reaume
(unpublished observations)]. XDH is not synthesized in the
adult eye, but is transported there [Reaume et al., 1989].
Designation applied to the site at -1145 in ry+4
that is responsible for the higher than normal XDH CRM of that
allele (i.e., ry409H vs. ry409N, the normal alternative;
Curtis, Clark, Chovnick, and Bender, 1989, Genetics
122: 653-61). Enzyme activity two to three times that of
other ry+ alleles (Chovnick, Gelbart, McCarron, Osmond, Candido, and Baillie, 1976, Genetics 84: 223-55); large tissue-specific increase in specific activity observed in late
third-instar larval fat body, but not Malpighian tubules; mRNA
levels 3.2 times higher than normal (Covington, Fleenor, and
Devlin, 1976, Genetics 84: 211-32; see also Clark, Daniels,
Rushlow, Hilliker, and Chovnick, 1984, Genetics 108: 953-68).
Maps genetically to the right of ry1005 (Clark et al., 1984).
Designation applied to the site at -1701 in ry+10
that is responsible for the lower than normal XDH CRM of that
allele (i.e., ry1005L vs. ry1005N, the normal alternative)
(Curtis, Clark, Chovnick, and Bender, 1989, Genetics
122: 653-61). Enzyme levels 50% those of other normal alleles
(McCarron, O'Donnell, Chovnick, Bhullar, Hewitt, and Candido,
1979, Genetics 91: 275-93); mRNA levels 52% normal (Covington, Fleenor, and Devlin, 1976, Genetics 84: 211-32). Maps
genetically to the left of ry409 (Clark, Daniels, Rushlow,
Hilliker, and Chovnick, 1984, Genetics 108: 953-68).