40 MOLECUL-ES, VIRUSES, AND BACTERIA 



nucleic acid (DNA) of the chromosomes of a cell or a virus. Thus far 

 the only exceptions to this rule are the viruses containing ribonucleic 

 acid (RNA), and here it is the RNA that is presumed to carry the 

 genetic code. All heritable differences can be ascribed to differences in 

 the base sequence of the nucleic acids of cells. The base sequence of 

 genetic DNA or RNA is perpetuated during the replication of the 

 macromolecule. An ingenious mechanism for this replication was pro- 

 posed by Watson and Crick ( 1953 ) concommitantly with their formu- 

 lation of the structure of DNA. Considerable evidence suggests that 

 their proposal is correct (Levinthal, 1956; Meselson and Stahl, 1958; 

 Taylor, Woods, and Hughes, 1957 ) . 



The genetic phenomena of intrachromosomal recombination and 

 gene mutation are assumed to be due to alterations of base se- 

 quences by one of several possible processes. This theory implies 

 that any genetic unit of structure or function can be defined in terms of 

 a nucleotide sequence of a given quality or length. Clearly, many types 

 of units can be expected to be found. There may be a minimum length 

 of sequence which can undergo replication, or a minimum sequence for 

 determining the structure of a particular macromolecule. In the syn- 

 thesis of a protein, for example, there is reason to beheve that short 

 sequences determine the incorporation of each amino acid in a poly- 

 peptide chain; each such sequence is a small functional unit. The sum 

 of all these sequences, in proper order, determines the polypeptide 

 chain as a whole. Thus, the nucleic-acid code spells out "words" and 

 also fits those words together to make "sentences." In higher organ- 

 isms, in which differentiation and aging take place, there is a time 

 sequence of events which may also be, in part or totally, controlled by 

 the nucleic-acid code. To what kind of organization of sequences this 

 may be due, we cannot even guess as yet. 



The tool with which a geneticist dissects the genome of an or- 

 ganism is called recombination analysis. The first task of the molecular 

 geneticist is to understand recombination in terms of molecular struc- 

 ture. There is no mystery as to why genes situated on different, non- 

 homologous chromosomes are reasserted independently at meiosis: 

 each pair of homologous chromosomes is an independent physical 

 entity, and it is distributed independently at meiosis. The recombina- 

 tion that interests us is the one called crossing-over (reciprocal ex- 

 changes between a pair of homologous chromosomes), for this kind 

 of recombination informs us how the chromosome is organized and, 

 perhaps, how it is duplicated. Ten years ago, crossing-over was a dead 

 subject; the group of cytologists led by C. D. Darlington had offered a 

 complete explanation of the phenomenon. Their explanation was es- 

 sentially mechanical. At meiotic pairing, which is visible cytologically, 

 each homologue of a pair is already double, but the two strands do not 



