Mutations with multiple independent origins in surface antigens mark the targets of biological selective pressure

Abstract

This manuscript documents the existence and importance of a small subset of mutations in Plasmodium falciparum genes that continually reoccur in separated populations. Here we describe how to identify recurrent mutations using a novel application of pre-existing computer programs designed to trace genealogy. Perhaps the most striking example of this phenomenon occurs in the cytotoxic T-cell epitope of a malaria surface antigen, the circumsporozoite (CS) protein of P. falciparum, where identical sequence types clearly have multiple independent origins. The importance of this observation is that it conclusively demonstrates selective pressure on these sequences and indicates that there is a significant natural mechanism relating to the circumsporozoite protein that affects the success of malaria sporozoites.