Calvin Bridges
and the Development of
Classical Genetics

The Fly Room is usually identified with Thomas Hunt Morgan and his students Calvin Bridges, Alfred Henry Sturtevant, and Hermann Joseph Muller. I was too young to have met Bridges and Morgan, but I did my Ph.D. with Muller, and I had opportunities to meet Sturtevant at genetics meetings and when I visited Caltech. I also knew Edgar Altenberg, Muller's high school chum, who was an active discussant in the Fly Room findings. Later I met Katherine Brehme Warren at Cold Spring Harbor and when she visited Muller's laboratory at Indiana University.

To my mind, Calvin Bridges made three major contributions to the development of classical genetics. The first – his analysis of nondisjunction – is probably his most famous and remarkably it was also his Ph.D. thesis. Bridges had coined the term "nondisjunction" earlier in a 1913 paper. Nondisjunction is the failure of a pair of chromosomes to separate during cell division. In his 1916 publication “Non-disjunction as Proof of the Chromosome Theory of Inheritance,” Bridges used both the sex chromosomes and the white-eyed mutation to illustrate the fate of those eye colors in various offspring from females who carried a Y chromosome or males who were sterile because their X chromosome-bearing sperm encountered an egg lacking any sex chromosomes. The correlations were striking, and one of the features of Bridges’ dissertation is its exhaustive examination of every possible combination that could arise and the predictions he could make for any given cross. This paper, along with his earlier 1913 and 1914 papers, proved the experimental proofs for the linkage, or relationship, between genes and chromosomes.

Bridges’ second most famous work was the balance theory of sex determination. It was early recognized that the Y chromosome in fruit flies was not male determining. XO flies were sterile males, identical in sexual appearance and sexual behavior to XY males. XXY flies were females and fertile. XXX triploid females were fertile females and that led to offspring that were XXY triploids or XX triploids that were intersex flies (i.e., they had a complex mixture of male and female parts). Flies that were XXX, but otherwise diploid, were females but somewhat bedraggled from the excess production of the extra X chromosome. Bridges proposed a ratio of X chromosomes to autosome status. Thus 1 X:2A is a male at 0.5 and 2X:2A is a female at 1.0. The flies that are 2X:3A are intersex at 0.67 and flies that are 3X:2A at 1.5 are “super females” as he (not so accurately) described them. The 3X:3A, of course is 1.0 again and a perfectly fertile female. In the 1960s sex determination in humans and other animals was shown to be different. In these cases, the Y chromosome is male determining and thus XXY humans are sterile males with Klinefelter syndrome and XO humans are sterile females with Turner syndrome.

Bridges’ third major contribution to genetics was his evolutionary interpretation of the salivary chromosome bands associated with larvae. Theophilus S. Painter had found them, and Bridges quickly began correlating gene mutations to salivary band locations using deletions, duplications, and translocations of chromosomes. He noted that some mutations, like bar eyes, were associated with duplications of a band. He called these repeats. Muller had independently found this duplication for bar eyes, and he called these tandem duplications associated with unequal crossing over. Bridges and Muller in 1935 and 1936 independently extended this finding to the evolution of genes. Bridges died in 1938 before the field of pseudoallelism opened up. But Nobelist Edward B. Lewis recognized the importance of Bridges’ repeat hypothesis and used it to generate his own theory of pseudoallelism at the bithorax locus and to construct the evolution of homeotic mutations associated with wing, leg, and thorax formation.

Ironically, fruit fly geneticists today know of Bridges for his book, The Mutants of Drosophila melanogaster (1944), completed by his student Katherine Brehme Warren and published after his death. Bridges had taken on the job of mapping each new mutation found and constructing the maps for all four pairs of chromosomes, using the mapping methods worked out by Sturtevant (the linear linkage that he initiated) and by Muller (the coincidence and interference corrections for mapping of nearby genes). “Bridges and Brehme” was the geneticist’s encyclopedia, a constant resource for the next 20 years for the map location, phenotype, alleles, and major initial publications on every known mutation in
fruit flies – and the precursor to today’s FlyBase.

Elof Axel Carlson

↑ Morgan’s Lab