Genome Immunobiology RIKEN Hakubi Research Team
Can an organism’s germline genome, the genetic legacy it contributes to its progeny, be altered based on its individual life experiences? The canonical answer to this question is “no.” The alternative is linked to a caricature of Lamarck, but Darwin also proposed that acquired characteristics were inherited, via trafficking of tiny somatically-produced “gemmules” to the germline. This idea was rejected in favor of Weismann’s proposed barrier isolating the germline from influence by the soma. However, recent studies demonstrate horizontal gene transfer (HGT) to animal germlines, suggesting that Weismann’s barrier is not impenetrable.
We are fascinated by several examples of this unconventional mode of evolution, including the discovery of endogenous non-retroviral sequences in mammalian germline and somatic genomes (Horie et al., Nature 2010). We are testing the hypothesis that small RNAs transcribed from some of these sequences allow RNA interference against viruses (Parrish et al., RNA 2015), analogous to the CRISPR/Cas immune system observed in prokaryotes (Ophinni et al., Trends in Immunology 2019). We have documented endogenization and excision of human herpesvirus 6 in human genomes (Liu et al., PLoS Genetics 2020; Kojima et al., PLoS Genetics 2021) and are studying the consequences of these processes on human immunity and disease risk. In addition to viruses, non-viral mobile genetic elements (MGEs) often mediate HGT and can also be horizontally-transmitted themselves; in general, we study how organismal phenotypes, especially those related to immunity, emerge from mutations involving MGEs.
Team Leader: Nicholas F. Parrish, M.D. Ph.D.
1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045