ALIGNMENT OF 700 GLOBIN SEQUENCES - EXTENT OF AMINO-ACID SUBSTITUTIONAND ITS CORRELATION WITH VARIATION IN VOLUME

Seven-hundred globin sequences, including 146 nonvertebrate sequences, were aligned on the basis of conservation of secondary structure and the avoidance of gap penalties. Of the 182 positions needed to accommo date all the globin sequences, only 84 are common to all, including th e absolutely conserved PheCD1 and HisF8. The mean number of amino acid substitutions per position ranges from 8 to 13 for all globins and 5 to 9 for internal positions. Although the total sequence volumes have a variation similar to 2-3%, the variation in volume per position rang es from similar to 13% for the internal to similar to 21% for the surf ace positions. Plausible correlations exist between amino acid substit ution and the variation in volume per position for the 84 common and t he internal but not the surface positions. The amino acid substitution matrix derived from the 84 common positions was used to evaluate sequ ence similarity within the globins and between the globins and phycocy anins C and colicins A, via calculation of pairwise similarity scores. The scores for globin-globin comparisons over the 84 common positions overlap the globin-phycocyanin and globin-colicin scores, with the fo rmer being intermediate. For the subset of internal positions, overlap is minimal between the three groups of scores. These results imply a continuum of amino acid sequences able to assume the common three-on-t hree alpha-helical structure and suggest that the determinants of the latter include sites other than those inaccessible to solvent.