Biochemistry and Evolution 51 



here and there all over the animal kingdom, in many members of 

 many invertebrate groups as well as in vertebrates generally. Keilin 

 suggested many years ago that the formation of hemoglobin is due to 

 modifications (presumably mutational) in the enzymatic machinery 

 ordinarily involved in the production of the cytochromes. Presumably 

 b or c are the components concerned, since their hemes are very 

 closely related to that of hemoglobin itself. This seems to be con- 

 firmed by the comparable fact that chlorocruorin, which occurs only 

 in a small group of so-called chlorhemid worms, carries a heme very 

 similar to and possibly identical with that of cytochrome a. 



According to all available evidence, different hemoglobins possess 

 a common heme, and the species-specific differences existing between 



Pantoic acid 



. A 



OH CH, OH ^-Alanine 



.A_ 



= P 0CH 2 C CHCO NHCH 2 CH 2 CO NHCH 2 CH 2 SH 



OH CH 3 



v r J 



Pantothenic acid 



Pan tetheine-4 1 — phosphate 

 FIG. 1. Requirements for coenzyme A synthesis by bacteria l see also Table 2). 



them reside entirely in the globin part of the molecule, But this may 

 be too narrow a view, for there may well be mutant forms of globin 

 as indeed there are among humans. About two dozen or so human 

 variants are now known ( Prankerd, 1961) and what seem to be quite 

 trivial differences from the purely chemical standpoint may have im- 

 portant physiological results: sickle-cell hemoglobin differs from nor- 

 mal in only one of the 300 amino acid units in each half molecule 

 (Hunt and Ingram, 1959). In sickle-cell hemoglobin, valine replaces 

 glutamic acid, while in hemoglobin C the place of glutamic acid is 

 taken by lvsine. These and other differences are summarized in 

 Table 3. Small though the chemical differences between the normal 

 and sickle-cell hemoglobins may seem on the surface, individuals 

 carrying two sickle genes commonly die, often in infancy, from the 

 .consequent anemia. Here we have what was originally an advanta- 



