EVOLUTION OF THE CRYPTIC FMR1 CGG REPEAT

We have sequenced the 5' untranslated region of the orthologous FMR1 g ene from 44 species of mammals. The CGG repeat is present in each spec ies, suggesting conservation of the repeat over 150 million years of m ammalian radiation. Most mammals possess small contiguous repeats (mea n number of repeats = 8.0 +/- 0.8), but, in primates, the repeats are larger (mean= 20.0 +/- 2.3) and more highly interrupted. Parsimony ana lysis predicts that enlargement of the FMR1 CGG repeat beyond 20 tripl ets has occurred in three different primate lineages. In man and goril la, AGG interruptions occur with higher-order periodicity, suggesting that historical enlargement has involved incremental and vectorial add ition of larger arrays demarcated by an interruption. Our data suggest that replication slippage and unequal crossing over have been operati ve during the evolution of this repeat.