A TRINUCLEOTIDE REPEAT-ASSOCIATED INCREASE IN THE LEVEL OF ALU RNA-BINDING PROTEIN OCCURRED DURING THE SAME PERIOD AS THE MAJOR ALU AMPLIFICATION THAT ACCOMPANIED ANTHROPOID EVOLUTION

Nearly 1 million Alu elements in human DNA were inserted by an RNA-med iated retroposition-amplification process that clearly decelerated abo ut 30 million years ago. Since then, Alu sequences have proliferated a t a lower rate, including within the human genome, in which Alu mobili ty continues to generate genetic variability. Initially derived from 7 SL RNA of the signal recognition particle (SRP), Alu became a dominant retroposon while retaining secondary structures found in 7SL RNA. We previously identified a human Alu RNA-binding protein as a homolog of the 14-kDa Alu-specific protein of SRP and have shown that its express ion is associated with accumulation of 3'-processed Alu RNA. Here, we show that in early anthropoids, the gene encoding SRP14 Alu RNA-bindin g protein was duplicated and that SRP14-homologous sequences currently reside on different human chromosomes. In anthropoids, the active SRP 14 gene acquired a GCA trinucleotide repeat in its 3'-coding region th at produces SRP14 polypeptides with extended C-terminal tails. A C --> G substitution in this region converted the mouse sequence CCA GCA to GCA GCA in prosimians, which presumably predisposed this locus to GCA expansion in anthropoids and provides a model for other triplet expan sions. Moreover, the presence of the trinucleotide repeat in SRP14 DNA and the corresponding C-terminal tail in SRP14 are associated with a significant increase in SRP14 polypeptide and Alu RNA-binding activity . These genetic events occurred during the period in which an accelera tion in Alu retroposition was followed by a sharp deceleration, sugges ting that Alu repeats coevolved with C-terminal variants of SRP14 in h igher primates.