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 in some organisms where large portions of genomic DNA, ranging from 0.5% to 95% of the germline genome, is lost during early embryogenesis, meiosis, sex determination, and macronucleus formation (ciliates). DNA elimination is highly selective and reproducible and is an integral part of biology for diverse species. It results in distinct genomes in different cells or nuclei within an organism.
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 (see top figure for examples). 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. Despite being the subject of much interest and speculation, little is known about the functions and mechanisms of DNA elimination, particular in the hundreds of metazoan species that include a broad spectrum of invertebrates and vertebrates.
My lab is developing and using two models, 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, including genomics and bioinformatics, molecular biology, cell biology, biochemistry, and genetics, to establish both in vitro and in vivo systems to study DNA elimination. We aim to address some of the outstanding questions in metazoan DNA elimination, including: What functions does DNA elimination 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 players involved?
Our studies on programmed DNA elimination in various models may provide novel insights into 1) the functions and evolutionary advantages of DNA elimination, 2) the molecular mechanisms of DNA breaks, repair, and genome maintenance; 3) the origin and evolution of metazoan DNA elimination; and 4) potential new therapies for a parasitic nematode, Ascaris, that infects close to a billion people.
Watch a 7 min MicNite talk about our work on DNA elimination: