88 J. HERBERT TAYLOR 



a variable amount of exchange characteristic for each type of genetic 

 organization occurs in those forms with the smalh-st chi-oniosomos as 

 well as those with the largest ones. 



V. Sequences of Replication of DNA in Chromosomes 



As already noted, DNA replication is a discontinuous process during 

 the cell cycle. In cells of higher forms the period of synthesis may be 

 6 to 8 hours or perhaps longer in some cells. Even in cells where replica- 

 tion is completed in much less time, the period is long compared to the 

 time required to synthesize most large molecules. Therefore, the ques- 

 tion of the sequence of replication and its control has often been 

 raised. Evidence at the molecular level is very scarce. The mechanism 

 in which nucleotides are added at the 3' OH ends by DNA polymerase 

 (Chapter I) would appear to require a sequential addition. In addition, 

 the failure to find particles with the whole range of densities when a 

 density label is introduced into a replicating system has led to the sug- 

 gestion that there are few growing points at any moment during the S 

 period. However, the only direct evidence relating to the sequence of 

 replication has been obtained at the level of the chromosome by use of 

 tritium-labeled DNA. These studies now clearly indicate that there are 

 control mechanisms that operate to control the replication among 

 chromosomes within a single nucleus as well as the sequence or order 

 of replication within a single chromosome. This type of control probably 

 has a structural basis (see Section VII on chromosome models). 



The first indication of asynchronous replication within chromosomes 

 was the observation that the regions around the centromeres were repli- 

 cated late in root cells of Crepis (Taylor, 1958b). Later Lima-de-Faria 

 (1959) found that the X-chromosome of a grasshopper continued its 

 replication longer than the autosomes. Taylor (1960c) reported a rather 

 complex control in cells of Chinese hamster involving both sex chromo- 

 somes and autosomes. Lima-de-Faria (1959) had suggested that the late 

 replicating DNA was located in heterochromatin, but the two X-chro- 

 mosomes of the Chinese hamster female were different in their replica- 

 tion. These observations suggested that the pattern of replication was a 

 genetic trait, and like other genetic factors could mutate. If late replica- 

 tion was a characteristic of heterochromatin, this state was also mutable 

 or subject to change at certain stages of differentiation (Lyons, 1961 ; 

 Morishima et al., 1962). Recent studies (Morishima et al., 1962) have 

 shown that the heterochromatic X-chromosome of the female human 

 complement is late in completing its replication compared to its homol- 

 ogous mate and to most of the autosomes. 



