8 CELL HEREDITY 



orgiuiisms. For example, in the DNA of eertain bacterial viruses, all of 

 the cytosine is replaced by S-hydroxymethy! cytosine; in the DNA of 

 some plants, 5-methyl cytosine replaces a part of the cytosine; and in 

 certain cells, DNA is found to contain small amounts of other bases. 

 With respect to sugars, only ribose (in RNA) and deoxyribose (in DNA) 

 have been found, except for glucose which is present in addition to 

 deoxvribose in the DNA of some bacterial viruses. 



Each polynucleotide chain has a sugar-phosphate backbone, built of 

 phosphodiester linkages which connect the phosphate of one nucleotide 

 to the sugar of the next. The nitrogen bases project out from this back- 

 bone at angles of about 50°, differing slightly from base to base. 



The precise linear order of nucleotides in the polynucleotide chain is a 

 matter of great importance to the geneticist. If nucleic acids are hered- 

 itary material, they must be capable of a tremendous diversity of form in 

 order to carry all the genetic information of the cell. The most apparent 

 basis for such diversity between different nucleic acid molecules lies in 

 the nucleotide sequence, which can be thought of as a code. If each of 

 the four nucleotides of DNA, for instance, represents a different symbol, 

 or letter of a four-letter alphabet, then words or messages can be com- 

 posed on the basis of nucleotide sequence along the polynucleotide 

 chain. At present, it seems very likelv that nucleotide sequence provides 

 a basis for individuality among the nucleic acid molecules of the cell. 

 The available chemical evidence is consistent with this view. 



Ideally, one would like to determine the actual linear order of bases in 

 a nucleic acid molecule, but, if each cell contains a great variety of 

 different types of molecules, the first problem is that of isolating one kind 

 of molecule from the others. Until this feat is accomplished, total se- 

 quence analysis would be pointless. On the other hand, some indirect 

 approaches to the question have been very revealing. Certain regularities 

 in base composition have been established, as shown in Table 1.2. In all 

 samples of DNA and RNA thus far analyzed (except the NAs of some 

 viruses), the number of 6-keto groups equals the number of 6-amino 

 groups. Adenine and cytosine each contain an amino group in the 6- 

 position; and guanine, uracil, and thymine each contain a 6-keto group. 

 The total number of adenines plus cytosines equals the total of guanines 

 plus thymines in DNA, and of guanines plus uracils in RNA. There is a 

 further regularity observed in DNA samples which is not found in most 

 RNA's, namely, the molar ratio of adenine to thvmine is one, and 

 that of cytosine to guanine is one. Consequentlv, the sum of the 

 purines equals the sum of the pvrimidines. However, the amount of 

 adenine plus thymine relative to guanine plus cvtosine varies con- 

 siderably from species to species, as can be seen in Table 1.2. 



