L1 A-MONOMER TANDEM ARRAYS HAVE EXPANDED DURING THE COURSE OF MOUSE L1 EVOLUTION

LlNE-1 (L1) is a family of highly repeated DNA sequences interspersed throughout the mammalian genome. Individual Ll elements are thought to be generated by a transposition mechanism involving reverse transcrip tion of an RNA intermediate followed by insertion into a new genomic s ite. In mice, three major families of L1 elements, termed ''A,'' ''F,' ' and ''V,'' have been defined on the basis of the sequence found at t he 5' terminus. Previous analyses of A-monomers have demonstrated sequ ence heterogeneity among individual A-monomers, variation in the lengt h of A-monomer sequences, and the presence of transcriptional regulato ry activity. To provide a detailed characterization of A-monomers as a foundation for studying their transcriptional regulatory activity, we have analyzed the sequences of 39 complete or partial length A-monome rs from 20 different mouse Ll elements. A-monomers can be classified i nto six different types according to shared-sequence length variations . Consensus sequences for the six types of A-monomers indicate conserv ation of possible transcription factor-binding sequences. Specific sub groups of A-monomers correlate with the relative dispersal time of a m ouse Ll element. A phylogenetic analysis of A-monomers indicates that the length variants represent good diagnostic sites for phylogenetic s ubgroups of A-monomer sequences. These observations suggest a model fo r the evolution of A-monomer tandem arrays that involves stepwise muta tion and array expansion in the 5' direction. Hybridization data provi de a minimum estimate of 16,000 copies of the A-monomer sequence in th e mouse haploid genome, with an average array length of 2.1 monomer un its.