Severe Distortion by 5-Bromouracil of the Sequence Characteristics of a Bacterial Deoxyribonucleic Acid

THE statement is often encountered in the literature that one or another purine or pyrimidine analogue, not found in the cell normally, can, when it is incorporated into a deoxy- or ribo-nucleic acid, partly replace one of the natural nucleic acid constituents. For example, 5-bromouracil is said to replace some of the thymine in deoxyribonucleic acid, or 5-fluorouracil some of the uracil of ribonucleic acid ; and this view is even applied to minor constituents occurring in Nature, 5-methylcytosine replacing some of the cytosine, pseudouridine some of the uridine. Such statements are derived, implicitly, from the complementariness principles formulated in this laboratory for deoxyribonucleic acid 1 and ribonucleic acid 2 . But what actually is meant by replacement ? If, as is the case, the molar sum of the 6-aminopyrimidines cytosine and 5-methylcytosine equals the molar concentration of the 6-ketopurine guanine in the deoxyribonucleic acid of rye germ 3 , does this signify that every cytosine molecule along the polymer chain has an equal chance of being ‘replaced’ by a methylcytosine molecule ? We have recently discussed the evidence for this not being the case 3 .