L1 retrotransposable elements account for at least 30% of all mammalian genomes. L1 transposition is active in present day mammals and causes up to 0.2% of the genetic defects in humans. Full length mammalian L1 elements are 6-7 kb and all share the same organization: a 5' UTR which includes a regulatory sequence; ORF I, which encodes a protein of unknown function; ORF II which encodes a reverse transcriptase; and a 3' UTR that contains a G-rich polypurine:polypyrimidine tract and terminates in an A-rich sequence. Most of what is known about the mechanism of L1 regulation, replication, and transposition has been derived from evolutionary studies carried out by us and others. These studies have generated to two kinds of information: First, comparisons between different L1 families or L1-like elements has identified and assigned possible functional significance to the various L1 structural components. Second, it is now clear that L1 evolution is a paradigm for a novel evolutionary process that is taking place within the """"""""ecosystem"""""""" of the mammalian genome and that l1 evolution is quite dynamic, with novel L1 variants continually emerging over relatively short periods of time. As a consequence, L1 evolution has generated a rather complex family structure and we have exploited this feature of L1 DNA evolution to examine the phylogenetic history of their mammalian hosts. Over the past year we have extended our knowledge on the properties of the L1 regulatory sequence, on the evolutionary dynamics of l1 elements and more fully developed the use of l1 DNA as a phylogenetic tool. We previously showed that the regulatory region of the rat L1 element strongly stimulates the activity of a gene fused to it which was the first evidence that L1 DNA is not just some non-functional """"""""junk"""""""" DNA. We now know that the l1 regulatory region is not a typical transcriptional activator sequence but may stimulate gene activity by acting as an activator of protein translation. We have identified a hypervariable region in the part of the ORF I sequence that encodes glutamine motifs, suggesting that this motive is important for the function of ORF I> We also found that closely related L1 subfamilies may compete with each other and that L1 families may retain some transpositional activity for millions of years. And, finally, we have used L1 DNA as a phylogenetic tool to determine the phylogeny of Rattus sensu strictu a group that so fa has been refractory to standard taxonomic techniques.
