514 ANNUAL REPORT SMITHSONIAN INSTITUTION, 1961 



In the last 10 years many more biochemical systems under simple 

 genetical control have been found in man. Most conveniently for 

 practical purposes, the majority of them are expressed in some way in 

 the blood, and so they can be investigated by using portions of speci- 

 mens obtained for blood grouping. The number of known systems of 

 this kind is rapidly increasing. Those who discover them are usually 

 aware immediately of their possible anthropological significance and 

 soon carry out surveys of a number of different populations, between 

 which, as a rule, significant differences in gene frequency are found. 

 Many of the substances involved have known physiological functions : 

 among these are the haptoglobins and the transferrins, classes of 

 plasma proteins involved in different stages of iron metabolism. 

 Genetically determined variations in the control mechanisms of such 

 important vital processes are likely to be subject to intense natural 

 selection, and hence perhaps to be relatively short-term population 

 markers, but the details of the mechanisms of selection are in most 

 cases not yet known. 



One system where something is known of the selective mechanism 

 is that involving a genetically determined deficiency of the enzyme 

 glucose-6-phosphat6 dehydrogenase (sometimes called G6PD). The 

 normal biochemistry of this enzyme has long since been well estab- 

 lished, and empirically, though the chain of biochemical events is not 

 entirely clear, a deficiency of it is found to cause a liability to hemolytic 

 or blood-destructive anemia following the consumption of certain 

 drugs or of the common broad bean, Vicia faha, leading in the latter 

 case to f avism, a condition long familiar in Mediterranean populations. 

 The gene involved is unique, or nearly so, among those known to give 

 rise to human polymorphisms, in being sex-linked, or carried on the 

 female-determining X chromosome. Thus the male, with only one X 

 chromosome, either has the condition fully developed or not at all. 

 Unlike some other sex-linked genes, such as those for hemophilia and 

 color blindness, this one is readily recognizable in female heterozygotes, 

 but there is a quantitative overlap with homozygotes. Thus surveys 

 of gene frequency can be reliably carried out only on males. Rather 

 surprisingly, population studies leave little doubt that this apparently 

 harmful gene is, like those for sickle-cell hemoglobin and for thalas- 

 saemia, in some way protective against malaria. It may be that the 

 protected persons are the female heterozygotes. 



This large and growing class of known genetical systems with a 

 biochemical expression will thus almost certainly prove to include some 

 with gene frequencies fluctuating readily in response to changes in 

 external conditions, but it may be expected, like the blood-group 

 class, also to include others with gene frequencies stable over very long 

 periods. 



