U.S. Department of Health and Human Services
Research Summary/In Plain Language

Research in Plain Language

L1 retrotransposons are genetic parasites that are integrated into the DNA of all organisms studied to date, with the exception of strictly asexual organisms.  Because L1, like a virus, can replicate independently of its host, it can make multiple copies of itself and cause harm.  Consequently, natural selection will favor host processes that weaken L1 activity, but natural selection acting on L1 will also favor variants that can escape host defenses.  Eventually, L1 and its host should be in balance, but it may not last.  In fact, very early in mammalian evolution, this balance changed dramatically.  Unlike in nonmammalian species, where L1-generated DNA represents approximately 5 percent of genomic DNA, in mammals it accounts for approximately 50 percent of the DNA!  This actuality prompts a number of questions:  What happened to either L1 or its host to account for the success of mammalian L1?  How did this event change the biological properties and evolutionary history of both mammals and, in turn, L1 itself?

We carry out two types of studies on L1 elements.  The first one is aimed at understanding the biochemical properties and role in L1 replication of the L1-encoded ORF1 protein, which is essential for L1 replication.  The second one uses the L1 insertions laid down by now-extinct L1 families to study factors that affect the mutation rate.  This work resulted in the startling conclusion that DNA repair itself can cause mutations in nearby normal, undamaged DNA.  We have now demonstrated this experimentally and are intensively studying this process.​​