Chapter 32 



GENE ACTION 

 AND POLYPEPTIDES 



D 



k URING interphase, the nucleus 

 plays a very active and es- 

 sential role in the normal 

 metabolism of the cell. Let us make the 

 oversimplified assumptions that chromosomal 

 genes are the only nuclear components es- 

 sential for normal metabolism, and that all 

 of the features of metabolism unique to cells 

 are the consequence of gene action. On this 

 basis, then, all aspects of the phenotype that 

 are genetic in origin result from biochemical 

 effects of the genes. Because a cell contains 

 a great variety of chemical substances, we 

 expect one gene-initiated biochemical reac- 

 tion to lead to others which, in turn, will 

 lead to still others, forming a kind of tree 

 whose branches represent successive chemi- 

 cal reactions. Since all the branches would 

 be affected by the initial, gene-caused bio- 

 chemical change, we should find many differ- 

 ent chemical, physiological, and morphologi- 

 cal consequences of the initial change in the 

 fully-developed cell or individual. It is not 

 surprising, therefore, that a given genetic 

 change usually has many different effects 

 upon the phenotype and that most, if not 

 all, mutants have manifold or pleiotropic ef- 

 fects (Chapter 6). In tracing these pleio- 

 tropic effects back toward their origin, we 

 would expect the many different end effects 

 to be the consequence of fewer earlier-pro- 

 duced effects. Moreover, we would expect 

 their more primary causes to be based up- 

 on metabolic changes — changes sometimes 

 identifiable with modifications of particular 

 404 



chemical substances such as hemoglobin or 

 pituitary hormone (Chapter 6). 



With this orientation in mind, we can be- 

 gin a study of the biochemical basis of gene 

 action — biochemical genetics. Information 

 regarding the biochemical basis of gene ac- 

 tion may be gained by studying a trait such 

 as pigmentation, which, because it is describ- 

 able in chemical terms, may require rela- 

 tively few steps back to arrive at or near the 

 primary, gene-caused biochemical changes. 



Alcaptonuria 



In man, a rare condition detectable at birth 

 affects the color of urine. Though normal 

 in color when passed, it soon darkens on 

 contact with air and turns from light to dark 

 brown and finally to black. This character- 

 istic persists throughout the life of the indi- 

 vidual. 



Family, pedigree, and population studies 

 reveal that normal parents can have affected 

 children of either sex, and that affected chil- 

 dren appear with a much higher incidence 

 when their parents — both normal — are re- 

 lated. From the frequency of those affected 

 within families, and the finding that the 

 blackening of the urine is expressed fully 

 or not expressed at all, we can conclude that 

 affected individuals are homozygous for a 

 single pair of completely-recessive, auto- 

 somal genes. 



The blackening is due to the oxidation of 

 a substance in urine called alcapton or 

 homogentisic acid whose chemical descrip- 

 tion is 2,5-dihydroxyphenylacetic acid (Fig 

 urc 32-1). The disease is called alcapto- 

 nuria ' and affected individuals, alcaptonu- 

 rics. It should also be noted that several 

 pedigrees have been found in which appar- 

 ently the same phenotype is attributable to 

 the action of a single, dominant gene. Since 

 biochemical studies of dominant alcaptonura 

 have not been extensive, our attention is 



1 The account following is based upon the work of 

 A. E. Garrod and subsequent investigators. 



