264 Raphael Falk
bands of the stained vertebrate chromosomes (Q bands produced by quinacrine
hydrochloride, G bands produced by Giemsa, etc.).
Sensitive physical methods applied to the chromosomes of wild-type and large-
chromosomal aberration Drosophila stocks, established that eukaryotic chromo-
somes are composed of continuous DNA molecules running from one telomere,
through the centromere, to the other telomere [Kavenoff and Zimm, 1973]. Such
immense long molecules, it turned out, are replicated by multiple sites of replication-
initiation distributed along the DNA molecule [Huberman and Riggs, 1968].
Molecular analysis identified the fundamental unit of the basic strand of the
dense structure of the chromosome that is the relevant genetic structure. It has
the same type of design in all eukaryotes, the DNA molecule∼200 base pairs of
which are wrapped at intervals around octamers of histone-proteins as nucleosomes
[Kornberg, 1974]. The density of these nucleosomes changes with chromosomal
region and with the segment’s activity.
Centromeres turn out to be specific DNA segments that are controlled by genes
which ensure their properties of binding specific proteins for spindle attachment
and the suppression of any “normal” genes activity. The telomeres, on the other
hand, are regions of single-strand DNA that are maintained and replicated by a
complex of RNA-telomerase enzymes. These enzymes systems do fulfill significant
cell functions in controlling the length of the chromosome ends, that is essential
for cell longevity, and hence for controlling both senescence and tumorogenesis
[Blackburn, 1991; Cech, 2004].
4 GENETIC LINKAGE AS AN ANALYTIC STRATEGYNotwithstanding the cytogenetic evidence for the chromosomal theory of inher-
itance, the major support for the theory was derived from the phenomenon of
genetic linkage. Although linkage was not necessarily evidence for a chromosomal
theory, orvice versa, the notions mutually supported each other.
Already early on, when researchers probed the extension of Mendel’s rule of
independent segregation ofFaktorenin different species and for a variety of traits,
it became obvious that often there were significant deviations from the expected
independent segregation of traits. Was this due to some functional or developmen-
tal dependence of different traits on some common factor, or to an association of
the factors themselves? In more modern terms: were these cases of developmen-
tal or physiological pleiotropy, in which the same factor is involved in more than
one trait characteristic, or were Mendelian factors proper sometimes linked rather
than always segregating independently of each other? Note that the very term
“pleiotropy” (see Riegeret al. [1976]), like those of “penetrance” and “expres-
sivity” (see Falk [2000a]; Sarkar, [1999]) invented later, was primarily a semantic
technique to neutralize “disturbing” deviations from the dogma, even when even-
tually they may have served as handles to reach beyond the narrow essentialist
and reductionist notion of basic Mendelism.