Germline and somatic genomes are in general the same in a multicellular organism. Changes in the genome, particularly rearrangements or significant sequence loss, can be deleterious leading to disease, including chromosome abnormalities and cancer. A major exception to this genome constancy is programmed DNA elimination, a normal developmental process where portions of genomic DNA is lost during early embryogenesis or sex determination, resulting in an organism having two distinct genomes in different cells or nuclei.
Since its discover in 1887 by Theodor Boveri, DNA elimination was found in single-cell ciliates as well as in a variety of multicellular organisms across the tree of life. The broad phylogenetic distribution and differences observed suggest that DNA elimination likely evolved independently in different taxa, may serve various functions, and could be mechanistically diverse.
Understanding DNA elimination is a fundamental biological question as 1) it occurs in a broad spectrum of invertebrates and vertebrates; 2) its overall functions and evolutionary advantages remain an enigma; and 3) the DNA break and repair processes require high fidelity and regulation and are essential to genome maintenance.
My lab is developing and using two systems, nematodes and copepods, to carry out comparative analyses of the functions and mechanisms of metazoan DNA elimination. We are using a variety of molecular approaches and establishing both in vitro and in vivo systems to study DNA elimination. Among the outstanding questions are: What functions does it serve in different organisms? What are the mechanisms of DNA elimination? Do the DNA break and repair pathways use known/existing machineries of genome maintenance, or are there novel machineries involved?
Our studies on programmed DNA elimination may provide novel insights into 1) mechanisms of DNA breaks, repair, and genome maintenance; 2) the origin and evolution of metazoan DNA elimination; and 3) potential new therapies for a parasitic nematode that infects close to a billion people.
Watch a 7 min MicNite talk about our work on DNA elimination: