478 DANIEL MAZIA 



adduce convincing visual evidence for it (e.g. [(S]). The electron micro- 

 scopists present us with evidence of a still higher level of multiplicity, 

 though not with innnense numbers (e.g. [9, 10]). 



There is still a third level at which the complexity of the chromosome 

 must be considered; this involves elements which are not "genie" in the 

 usual sense, but may be consistent functional parts of a given chromosome. 

 One is the nucleolus (and nucleolar substance). In manv cells, there are 

 compact nucleolar bodies, associated with definite regions of given chromo- 

 somes. In addition, it has recently been shown that a nucleolar substance 

 is associated A\ith other regions of the chromosomes [i i]. Functionally, the 

 nucleolar equipment may be regarded as that part of the chromosome which 

 operates at the RNA stage of the DNA-RNA-protein relationship. (A 

 more specific statement would be difficult to make, and need not concern 

 us here.) A second functional eonipoiient of the chromosome, and the 

 one that is ot crucial importance for cell di\ision, is the kinetochore or 

 centromere. This is a distinct body, associated with each chromosome, 

 which is absolutely essential for its movements in ceM di\ ision. N'isually it 

 appears as the point at which the chromosome is engaged by the mitotic 

 apparatus; more crudely put, it is the "motor" of the chromosome. It is 

 not only essential but, if lost, is irreplaceable. In short, it meets one of the 

 fundamental recpiirements of a reproducing element. We know nothing 

 about its chemistry nor about any of its mechanisms, but its beha\ iour is 

 as exact and reproducible as that of any element of the cell. 



It has been necessary to summarize the evidence tor a chemical com- 

 plexity of the chromosome in order to raise an important biochemical 

 question of cell di\ ision ; when can we say that the whole chromosome has 

 reproduced and how does it reproduce } We are asking a question with 

 which Molecular Biology is bound to be confronted : how does a complex 

 and^ — on a molecular scale "three dimensional" body reproduce ? 



I ha\e recently suggested [i] that the reproduction of the whole chromo- 

 some is carried out by a "generati\e " method. Starting with a complete 

 chromosome, its DNA first reproduces by a genuine replication mechanism. 

 This is the exent ot concepfion of a new chromosome. We now have a 

 complete chromosome plus an additional allotment of DNA. The 

 "daughter" DNA now serves as the seed or centre for the development of 

 a complete daughter chromosome. This takes time, and will not be 

 completed, according to our fragmentarv e\idence, until the time of the 

 next following di\ ision. 



This picture ot a generati\e reproduction of the chromosome is more 

 easily understood from a diagram than from a \erbal description (Fig. i). 

 It gi\es us a sinifile reason why the chromosome is fundamentally a duplex 

 structure. In any system reproducing bv a generative scheme, where a 

 period ot dexelopment is required between conception and parturition, we 



