Biological Physics: Energy, Information, Life

88 Chapter 3. The molecular dance[[Student version, December 8, 2002]]

b

2 μm

0.25μm

d

200 μm

Figure 3.14:(Optical photomicrograph; schematic.) (a)Apolytene chromosome of the fruitflyDrosophila.Each
chromosome consists of 1000–2000 identical copies of the cell’s DNA, all laid parallel and in register; it is about
4 μmthick. Each visible band is a stretch of DNA about 100 000 basepairs long. Copyrighted figure; permission
pending.Koltzoff’s view of the structure of a polytene chromosome (bottom) as a bundle of straightened filaments,
each of diameterd.The normal chromosome seen during mitosis (top) consists of just one of these filaments, tightly
coiled.

Thus by a tour de force of statistical inference, Morgan and Sturtevant (together with C. Bridges
and H. Muller) partially mapped the genome of the fly, concluding that

• The physical carriers of genetic information are indeed the chromosomes, and


• Whatever the chromosomes may be physically, they are chains, one-dimensional
  “charm bracelets” of sub-objects—the genes—in a fixed sequence. Both the indi-
  vidual genes and their sequence are inherited.^6

By 1920 Muller could assert confidently that genes were “bound together in a line, in the order
of their linkage, by material, solid connections.” Like Mendel before them, Morgan’s group had
applied quantitative, statistical analysis to heredity to obtain insight into the mechanism, and the
invisible structural elements, underlying it.
There is a coda to this detective story. One might want to examine the chromosomes directly,
in order to see the genes. Attempts to do this were unsuccessful: Genes are too small to see with
ordinary, visible light. Nevertheless, by an almost unbelievable stroke of serendipity, it turned out
that salivary-gland cells ofDrosophilahave enormous chromosomes, with details easily visible in
the light microscope. N. Koltzoff interpreted these “polytene chromosomes,” arguing that they are
really clusters of over a thousand copies of the fly’s usual chromosome, all laid side by side in register
to form a wide, optically resolvable object (Figure 3.14). After treatment with an appropriate stain,
each polytene chromosome shows a characteristic pattern of dark bands. T. Painter managed to
discern differences in these patterns among different individuals, and to show that these were
inherited and in some cases correlated with observable mutant features. That is, at least some
different versions of a genome actuallylook different. Moreover, the observed linear sequence
of bands associated to known traits matched the sequence of the corresponding genes deduced
bygenetic mapping. The observed bands are not individual genes (these are still too small to
see under the light microscope). Nevertheless, there could be no doubt that genes were physical
objects located on chromosomes. Genetic factors, originally a logical construct, had becomethings,
the genes.

(^6) Later work by Barbara McClintock on maize would show that even the order of the genes along the chromosome
is not always fixed: Some genes are “transposable elements,” that is, they can jump. But this jumping is not caused
bysimple thermal motion; we now know that it is assisted by special-purpose molecular machines, which cut and
splice the otherwise stable DNA molecule.