BEXZER 



region in the wild-type "chromosome" 

 were to control the production of a 

 substance or substances needed for 

 reproduction of this phage in K cells. 



The phenotv'pic test for "pseudo- 

 allelism" leads to the division of the 

 region into two functionally distin- 

 guishable segments. These could be 

 imagined to affect two necessary 

 sequential events or could go to make 

 up a single substance the two parts of 

 which must be unblemished in order 

 for the substance to be fully active. 

 For example, each segment might 

 control the production of a specific 

 polypeptide chain, the two chains later 

 being combined to form an enzyme. 

 While it is not known whether this 

 sort of picture is applicable, a model 

 of this kind is capable of describing 

 the observed properties of the rll mu- 

 tants. The map position of a mutation 

 would localize a change in the region 

 (and also in the "enzyme" molecule), 

 the reversion rate would characterize 

 the type of change involved in the 

 genetic material, and the degree of 

 phenotypic effect would be an ex- 

 pression of the degree of resultant 

 change in the activity of the enzyme. 

 A "leaky" mutant would be one where 

 this latter effect was small. While no 

 obvious correlation has yet been ob- 

 served among these three parameters 

 of rll mutants, gne may well show up 

 upon more exhaustive study. 



"Clustering" of similar mutants sep- 

 arable by crossing-over has been ob- 

 served for several characters in phage 

 by Doermann and Hill and appears to 

 represent the rule. This may well be 

 the rule in all organisms, simply be- 

 cause functional genetic units are com- 

 posed of smaller recombinational and 

 mutational elements. One would ex- 

 pect to see this effect more readily in 

 phage because the probability of 

 recombination per unit of hereditary 

 material is much greater than for 

 higher organisms. 



281 



By extension of these experiments to 

 still more closely linked mutations, 

 one may hope to characterize, in mole- 

 cular terms, the sizes of the ultimate 

 units of genetic recombination, muta- 

 tion, and "function." Our preliminary 

 results suggest that the chromosomal 

 elements separable by recombination 

 are not larger than the order of a dozen 

 nucleotide pairs (as calculated from 

 the smallest non-zero recombination 

 v^alue) and that mutations involve vari- 

 able lengths which mav extend over 

 hundreds of nucleotide pairs. 



In order to characterize a unit of 

 "function," it is necessary to define 

 what function is meant. The entire rll 

 region is unitary in the sense that mu- 

 tations anywhere within the region 

 cause the rll phenotype. On the basis 

 of phenotype tests of trans configura- 

 tion heterozygotes, this region can be 

 subdivided into two functionally sep- 

 arable segments, each of which is esti- 

 mated to contain of the order of 4 X 

 10^ nucleotide pairs. If one assumes 

 that each segment has the "function" 

 of specifying the sequence of amino 

 acids in a polypeptide chain, then the 

 specification of each individual amino 

 acid can as well be considered a uni- 

 tary function. It would seem feasible, 

 with this system, to extend genetic 

 studies even to the level of the latter 

 functional elements. 



Swmnary .—\t has been discovered 

 that the mutations in the rll region of 

 phage T4 have a characteristic in com- 

 mon which sets them apart from the 

 mutations in all other parts of the 

 map. This characteristic is a host-range 

 reduction, namely, a failure to produce 

 plaques on a host (K) lysogenic for 

 phage ^. The mutant phage particles 

 adsorb to and kill K, but normal lysis 

 and phage release do not occur. 



All mutants with this property are 

 located within a sharply defined por- 

 tion of the phage linkage map. Within 

 that region, however, their locations 



