Heterogeneity of Deoxyribonucleic Acid (DNA) 15 



the very brief report 2 of the solubility of only part (over 60%) of the 

 DNA of liver nuclei in strong sucrose solution. 



Under defined conditions, the DNA's of calf thymus and of wheat 

 germ yield dialyzable fragments and small non-dialyzable "cores" 

 (about 7% of the total) following prolonged treatment with deoxy- 

 ribonuclease. 3, 4 It has not yet been decided whether this result is due 

 to the presence in these DNA's of more than one DNA or whether 

 the nucleic acids are composed of molecules possessing regions differing 

 in susceptibility to the enzyme. The type of heterogeneity those ex- 

 periments reveal may be elucidated if the same technique is applied 

 to the various DNA fractions which are now available (vide infra). 



Heterogeneity with respect to the sites of binding of positively 

 charged dyes to DNA has been described. 5 These results may arise 

 from identical molecules whose linear structure is discontinuous or may 

 be due to mixtures of dissimilar molecules, each possessing its own set 

 of binding characteristics. 



Evidence of an inhomogeneous distribution of DNA within the 

 nucleus has also come from studies 6 on the susceptibility to deoxy- 

 ribonuclease. Depending upon the species examined, only 40 to 89% 

 of the DNA of isolated nuclei can be removed with the enzyme. The 

 resistance of some of the DNA to the action of the nuclease is not 

 due to the same phenomenon as the resistance of the non-dialyzable 

 "cores" referred to above, since removal of the basic protein with dilute 

 HC1 renders the resistant DNA fraction in nuclei susceptible to 

 digestion. 6 



The DNA of Streptococcus faecalis is present in that organism in 

 two forms ; one is soluble in dilute sodium hydroxide solution, whereas 

 the other is not and is apparently bound to polysaccharide. 7 



These various findings are reminiscent of our early studies 8 on the 

 heterogeneity of DNA in mammalian tissue. It was found that two 

 gross fractions could be obtained by subjecting the total DNA (ex- 

 tracted with strong salt solution) to high-speed centrifugation in 0.87% 

 NaCl. In this fashion, an insoluble (DNAi) and a soluble (DNA 2 ) 

 fraction were obtained. With the exception of the normal livers, a 

 number of organs of the adult rat yielded the two fractions in varying 

 ratios 9 depending upon the organ (Table 1). Normal liver contains 

 DNA 2 , but little if any DNAi. During regeneration following partial 

 hepatectomy, DNAi appears in large amounts but the DNA 2 content 

 remains constant. It is not known whether the high ratios for small 

 intestine and for regenerating liver are due to the high mitotic activity 

 of these tissues. 



