270 Raphael Falk
staggered. Whitehouse suggested that the rejoining of the DNA molecules took
place not by an end-to-end association of broken chains but by lateral association
of complementary segments from homologous regions, to give — when exchange
of chromatids took place — shorthybrid DNAsequences [Whitehouse, 1965, 318].
Holliday [1964] proposed a different model, according to which the initial sever-
ance in DNA was enzyme-induced in one chain of the same polarity in each of the
chromatids involved. According to this and later more sophisticated models, het-
eroduplexes — discordances of one or more nucleotide bases in paired strands of the
DNA — could occur in such hybrid-DNA segment, which calls for the involvement
of DNA-repair mechanisms. Such repair, when in the “right” direction, would
reconstitute the 2:2 relationship between the products of this meiosis. However, in
the “wrong” direction it would end up in a 3:1 segregation, i.e., in gene-conversion
(suppose that an A-T nucleotide base pair in one chromatid is confronted by a G-C
pair in the other, in otherwise identical sequences in both chromatids. If the hy-
brid DNA segment includes the above mentioned discordance, mispaired A-C and
G-T heteroduplexes would occur. If one heteroduplex is repaired to become A-T
and the other to become G-C, the 2:2 segregation at that site will be reconstituted.
If, however, both heteroduplexes are repaired to become A-T, a 3:1 segregation
ensues). Thus gene conversion was interpreted as a misrepair in an interaction
between chromatids at meiosis. This interaction between two chromatids, involv-
ing a hybrid DNA segment formation (with or without heteroduplexes) may be
resolved as an exchange between chromatids, or no-exchange. Once these notions
were introduced, the mechanical breakage-rejoining model of recombination was
replaced by recombination as an enzyme-driven process, amenable to biochemical
analysis (see Stahl [1979]).
The insight gained from “the novel feature”, namely the property of single
chains of nucleotides to pair by the matching of purine (adenine – A, guanine –
G) and pyrimidine (thymine – T – replaced by U – uridine in RNA, cytosine – C)
bases, DNA with DNA or RNA, was now extended to become not only a powerful
analytic tool of the mechanics of the chromosomal phenomena of heredity, but also
a major instrument of genetic engineering. Genetic analysis and its application
has become the science of hybridization at the molecular level.
5 GENES — THE ATOMS OF HEREDITY: FROM MULLER TO WATSON
AND CRICKIn 1956, in the Brookhaven Symposium, Herman J. Muller succinctly put up “two
basic questions, both as old as genetics but still warmly disputed”.
First, have we the right to speak of individual genes as separate bodies
rather than only as convenient mental isolates, conceptually cut out of
an uninterrupted genetic material, or chromosome, of dimensions far
larger than they? Second, if the expression “the individual gene” does
correspond to a material reality..., do we have a right to regard any,