510 ANNUAL REPORT SMITHSONIAN INSTITUTION, 1961 



frequent as the conquest of the environmental diseases brings into 

 prominence, and exposes to investigation, the hard and therapeutically 

 intractable residue of the congenital abnormalities. 



It should be mentioned that, largely as a result of the attention 

 paid to tlie sickling problem, several dozen other abnormal hemo- 

 globins are now known, a number of which are sufficiently common 

 in particular regions of the world to serve as valuable anthropological 

 markers. Their frequencies are probably also maintained in a state 

 of balanced polymorphism, but the mechanisms have not been worked 

 out. The chemical constitution of normal adult hemoglobin has 

 now been worked out almost completely, and that of many of the 

 abnormal varieties nearly or quite as fully. The chemical abnormali- 

 ties consist in the substitution of one amino-acid residue for another 

 in the molecule of this protein. The molecule is composed of two parts 

 (or rather, two pairs of identical parts), and substitution in each part 

 is controlled by a separate set of allelomorphic (or alternative) genes. 



HEMOGLOBINS AND NATURAL SELECTION 



In the relationship between normal and sickle-cell hemoglobins we 

 have the clearest example yet worked out of natural selection acting 

 upon the human species, but the fact that we are within reach of 

 being able to measure directly the effects of the selective process 

 implies that the frequencies of the genes concerned are labile, and 

 they can scarcely be used as long-term anthropological markers. 

 While, however, high frequencies of the abnormal or sickle-cell hemo- 

 globin gene are liable to rapid change from generation to generation, 

 low frequencies may persist for a very long time, as indicators that a 

 modern population is descended, at least in part, from an ancestral 

 one which possessed it and which was probably exposed to endemic 

 infection with malignant tertian malaria. In most cases this cer- 

 tainly means African ancestry, but the distribution of the sickling 

 condition in southern Asia and Europe as well as in Africa has led 

 Lehmann to suggest that its original center of dispersion lay in 

 southwest Asia. An alternative possibility is that mutation from 

 the normal to the sickle-cell hemoglobin gene has taken place inde- 

 pendently in a number of places, the new gene persisting and spread- 

 ing wherever malignant tertian malaria has been endemic. 



We are bound to assume the existence of selective forces favoring 

 the spread of other hemoglobins, especially hemoglobin C in West 

 Africa, and hemoglobin E in southeast Asia ; we do not know whether 

 these forces have operated as rapidly as that involving sickle-cell 

 hemoglobin, but the indications are that the gene for hemoglobin 

 E, at any rate, is a fairly stable part of the genetical picture of 

 southeast Asia. The gene or genes for thalassaemia are found in 

 the Mediterranean area as well as parts of Africa and Asia, and 



