Springer Online Journal Archives 1860-2000
Summary The problem of non-randomness of point mutations was reexamined using three sources of information: (1) Amino acid replacements in phylogenetically related proteins; (2) Hemoglobin variants observed in the present-day human population; (3) Base replacements in related RNA species. All the three approches give prima facie evidence for a higher incidence of transitions as compared with their expectation, if the direction of mutation would be random. In phylogenetically related proteins, this can hardly be explained by a selective advantage of these replacements (selection for maintenance of function). In hemoglobin variants, it seems to be caused neither by known functional restraints of the molecule conformation, nor by preferential ascertainment of polar replacements. A specific predominance of C ⇋ T (Cytosine ⇋ Thymine) as compared with A ⇋ G (Adenine ⇋ Guanine) transitions in phylogenetically related proteins can only partially be explained by closer “similarity” of the corresponding amino acid replacements. In present-day hemoglobin variants, however, most of the difference between C ⇋ T and A ⇋ G transitions can be accounted for by a higher expected proportion of polar replacements among C ⇋ T transitions. In the examined RNA species, transitions in general are more frequent than expected; however, there is no difference between C ⇋ T and A ⇋ G substitutions. On the basis of these combined data, it is concluded that transitions in general occur more frequently than expected, if the direction of mutation would be random. However, the higher frequency of observed C ⇋ T compared with A ⇋ G transitions can probably be caused by closer average similarity of the corresponding amino replacements in the phylogenetically related proteins, and by preferential ascertainment of polar replacements among present-day hemoglobin variants. As a side result, an apparently higher involvement of the G ≡ C base pair as compared with the A T base pair was observed in the related RNA species. At present, it cannot be decided whether this is due to some unknown selection factor, or to nonrandomness of the mutation process itself.
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