In Pursuit of the Gene

252 ¨ TRIUMPH OF THE MODERN GENE
dress, Curt Stern wrote that it was obvious that “before them stood a man
whose whole being was working to reach fundamental conclusions. Every
muscle in his face seemed to be thinking.” 25
While Muller touched on a variety of problems, his most penetrating
insight concerned the long-standing mystery of Bar, the eye-shape mutant
that had played a key role in determining the frequency of new lethals. As
first discovered by University of Illinois geneticist Charles Zeleny, around
1920, Bar mutants reverted to wild type at a strikingly high frequency (of 1
in 1,600 flies). Zeleny also noted that the high rate of reversion was found in
only females, and he inferred that the reversion might involve crossing
over, which was known to take place exclusively in females. Zeleny also observed
that homozygous Bar females occasionally gave rise to mutants with
extra-slitty eyes, which he called ultra-Bar, and these ultra-Bar mutants themselves
could revert either to normal Bar-eyed mutants or to wild-type flies.
Following up on Zeleny’s work in 1925, Sturtevant hypothesized that
the reversion and production of ultra-Bar from Bar was due to an unusual
type of recombination. As Sturtevant explained it, two homologous chromosomes
underwent crossing over at a point lying to the right of the Bar
locus in one chromosome and to the left of it in the other, producing one
chromosome that contained two Bar genes and one that contained neither.
According to Sturtevant, the chromosome with no Bar gene was the wild
type. At the same time, he cautioned that such a crossover seemed to defy
the normal mode of crossing over in which like genes were imagined to lie
side by side, and he was at a loss to explain how this could occur. 26
Muller had revisited Sturtevant’s idea about unequal crossing over in
1930, after his discovery that chromosomes were broken and rejoined with
a surprisingly high frequency and that, in the process, fragments were lost
or reattached to new chromosomes. In particular, he hypothesized that if a
chromosome broke into two (or more) fragments and, at the same time, a
nearby chromosome underwent a similar breakage into fragments, the
fragments might undergo a reattachment in a new configuration at their
broken ends. “In adopting this scheme,” Muller observed, “we accept the
principle that the rearrangements occur by a process which is virtually