Evolutionary selection against change in many Alu repeat sequences interspersed through primate genomes

Abstract

Mutations have been examined in the 1500 interspersed Alu repeats of human DNA that have been sequenced and are nearly full length. There is a set of particular changes at certain positions that rarely occur (termed suppressed changes) compared to the average of identical changes of identical nucleotides in the rest of the sequence. The suppressed changes occur in positions that are clustered together in what appear to be sites for protein binding. There is a good correlation of the suppression in different positions, and therefore the joint probability of absence of mutation at many pairs of such positions is significantly higher than that expected at random. The suppression of mutation appears to result from selection that is not due to requirements for Alu sequence replication. The implication is that hundreds of thousands of Alu sequences have sequence-dependent functions in the genome that are selectively important for primates. In a few known cases Alu inserts have been adapted to function in the regulation of gene transcription.