G. W. BEADLE 



urged that the two fields have much in common and that each stands 

 to profit through contact with the other. Through the eff"orts of these 

 individuals and others of like mind there are many instances known 

 in which the relation of genetics to biochemistry is so clear that it can 

 no longer be disregarded by intelligent investigators in either field. In 

 fact, from this relation there tends to emerge a new interest, known as 

 biochemical genetics, which promises to tell us what the genes do and 

 how they do it, on the one hand, and to lead us to further knowledge 

 in the ways of biosynthesis on the other. In both directions there 

 obviously lie many opportunities. 



One of the earliest instances in which a Mendelian trait could 

 be interpreted in terms of specific chemical reactions is that involving 

 the human disease known as alcaptonuria. In individuals homo- 

 zygous for the mutant gene responsible for this character, 2,5-di- 

 hydroxyphenylacetic acid (homogentisic acid or alcapton) is excreted 

 in the urine instead of being broken down to carbon dioxide and 

 water, as it is in persons receiving the normal form of the alcaptonuric 

 gene from one or both parents (15). Homogentisic acid is oxidized 

 to a black pigment on exposure to air and it is this process that is re- 

 sponsible for darkening of the urine, the most striking symptom of the 

 disease. According to Gross (cited by Garrod), alcaptonurics lack a 

 specific enzyme found in the blood of normal persons which catalyzes 

 the degradation of homogentisic acid. Alcaptonuria therefore repre- 

 sents the first recorded instance in which it could be said that a par- 

 ticular chemical reaction is controlled by a known gene through the 

 mediation of a specific enzyme. 



Within the past dozen years, additional examples have become 

 known in which organisms unable to carry out specific reactions differ 

 in a single gene from their chemically more successful relatives. In 

 flower pigment synthesis, for example, the formation of carotenoids, 

 anthocyanins, anthoxanthins, chalcones, and fiavocyanins is known 

 to be genetically controlled in one plant or another (7,24). Specific 

 oxidations of pelargonidin derivatives to cyanidin analogues and of 

 cyanidin compounds to delphinidin counterparts are dependent on 

 the activities of specific genes. The addition of sugars to anthocyani- 

 dins through glycosidal linkages and the transformation of the an- 

 thoxanthin quercetin-3-glucoside to the corresponding cyanidin-3- 

 glucoside are likewise unable to proceed if specific genes are modified. 



