Research in my laboratory is focused on eukaryotic mobile DNA, or transposable elements (TE). These elements may cause insertional mutations and are also known as junk DNA, selfish DNA, or genomic parasites, although this unfavorable view has recently been challenged by emergence of their role as drivers of genome evolution and important contributors to formation and function of heterochromatic chromosome compartments such as centromeres and telomeres. Genomic DNA may contain only a few TE copies, or, at the other extreme, may primarily consist of TEs (80-90%), with our own genome somewhere in between (~45%). Two major categories of TEs inhabit eukaryotic genomes: retrotransposons move via an RNA intermediate copied back into DNA by an element-encoded reverse transcriptase, while DNA transposons move only as DNA, most of them using an element-encoded transposase to perform cut-and-paste transposition. Retrotransposons, in turn, are typically subdivided into two large classes: LTR retrotransposons are structurally similar to vertebrate retroviruses and are framed by long terminal repeats (LTRs), while non-LTR retrotransposons, or LINEs, do not contain any such repeats and are often truncated at the 5' end. I became fascinated by mobile genetic elements as an undergraduate in a lab which discovered them, and, as may be seen from my publications, transposons have not stopped surprising me ever since.

One of my current research topics involves investigation of a recently described third class of eukaryotic retroelements, which is distinct from both non-LTR and LTR retrotransposons and forms a sister clade to telomerase reverse transcriptases (Arkhipova et al. 2003). These Penelope-like elements (named after the first described representative, Penelope from Drosophila virilis) possess a single open reading frame, which, in addition to an atypical reverse transcriptase domain, contains a unique GIY-YIG endonuclease domain, previously found in bacterial group I introns. An unusual feature of these elements is their ability to retain introns after transposition, which is apparently incompatible with reverse transcription of spliced RNA intermediates, and studies of their replication mechanisms should shed light on this interesting phenomenon. Also of interest is investigation of their phylogenetic distribution: they are very widespread and are found in at least ten animal phyla, but have been independently lost from many taxa, most notably from birds and mammals.

Another, closely related, topic is exploring the TE component in rotifers of the Class Bdelloidea, the largest metazoan taxon in which sexual reproduction is not known and neither males, hermaphrodites, or meiosis have ever been found. Transition to asexuality implies loss of several TE copy number control mechanisms that depend on sex. It is therefore expected that vertically-transmitted deleterious TEs cannot persist in long-term asexuals and should be lost, attenuated, or domesticated (Arkhipova and Meselson 2000, 2005a). Bdelloid rotifers contain a wide variety of DNA transposons, which are prone to horizontal transmission (Arkhipova and Meselson 2005b). In contrast, retroelements in bdelloids are notably under-represented. A very unusual bdelloid retroelement, named Athena, belongs to the Penelope-like class but is associated with telomeres and apparently has been recruited to perform an essential function of chromosome end maintenance. I am interested in understanding the characteristic features of this recruitment process, which may recapitulate the early events in eukaryotic evolution leading to the predominant telomerase-based pathway of chromosome end maintenance.

Finally, bdelloid rotifer genomes, in particular their telomeric regions, prove to be an exceptionally rich source of unconventional genetic material, such as numerous genes of apparently foreign origin. Many of these genes become pseudogenes, but others get recruited by the host to perform novel functions. Studies of some of these genes, which also reveal some unexpected connections to mobile elements, open an exciting new direction in our research.