L1 A-monomer tandem arrays have expanded during the course of mouse L1 evolution

LINE-1 (L1) is a family of highly repeated DNA sequences interspersed throughout the mammalian genome. Individual L1 elements are thought to be generated by a transposition mechanism involving reverse transcription of an RNA intermediate followed by insertion into a new genomic site. In mice, three major families of L1 elements, termed "A," "F," and "V," have been defined on the basis of the sequence found at the 5' terminus. Previous analyses of A-monomers have demonstrated sequence heterogeneity among individual A-monomers, variation in the length of A-monomer sequences, and the presence of transcriptional regulatory 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-monomers from 20 different mouse L1 elements. A-monomers can be classified into six different types according to shared-sequence length variations. Consensus sequences for the six types of A-monomers indicate conservation of possible transcription factor-binding sequences. Specific subgroups of A-monomers correlate with the relative dispersal time of a mouse L1 element. A phylogenetic analysis of A-monomers indicates that the length variants represent good diagnostic sites for phylogenetic subgroups of A-monomer sequences. These observations suggest a model for the evolution of A-monomer tandem arrays that involves stepwise mutation and array expansion in the 5' direction. Hybridization data provide a minimum estimate of 16,000 copies of the A-monomer sequence in the mouse haploid genome, with an average array length of 2.1 monomer units.