Transgenerational Inheritance of Diet-Induced Genome Rearrangements in Drosophila

Abstract

Ribosomal RNA gene (rDNA) copy number variation modulates heterochromatin formation and influences the expression of a large fraction of the Drosophila ge-nome. This discovery, along with the link between rDNA, aging, and disease, high-lights the importance of understanding how natural rDNA copy number variation arises. Pursuing the relationship between rDNA expression and stability, we have discovered that increased dietary yeast concentration, emulating periods of dietary excess during life, results in somatic rDNA instability and copy number reduction. Modulation of Insulin/TOR signaling produces similar results, indicating a role for known nutrient sensing signaling pathways in this process. Furthermore, adults fed elevated dietary yeast concentrations produce offspring with fewer rDNA copies demonstrating that these effects also occur in the germline, and are transgenera-tionally heritable. This finding explains one source of natural rDNA copy number variation revealing a clear long-term consequence of diet.

Modeling dietary influences on offspring metabolic programming in Drosophila melanogaster

“…Work in Drosophila has demonstrated a paternal contribution to metabolic programming (Valtonen et al , 2012b; Ost et al , 2014; Aldrich and Maggert, 2015). Exposure of male flies to a low-protein diet from embryo through adulthood resulted in progeny with shortened developmental times and larger male offspring, but no change in female offspring size, relative to paternal males raised on standard food (Valtonen et al , 2012b).…”

“…Taking full advantage of the benefits of fly genetics and dietary manipulation, two groups have uncovered profound insight into the mechanistic underpinnings of metabolic programming, highlighting a key role for genomic alteration (Ost et al , 2014; Aldrich and Maggert, 2015). Male flies fed a protein-rich diet exhibit decreased rDNA copy numbers resulting in rDNA instability in both somatic and germ cells which was InR-dependent (Aldrich and Maggert, 2015).…”

“…Male flies fed a protein-rich diet exhibit decreased rDNA copy numbers resulting in rDNA instability in both somatic and germ cells which was InR-dependent (Aldrich and Maggert, 2015). To investigate the impact on germline transmission, Aldrich et al crossed these male flies with females carrying an rDNA-deficient compound X chromosome to generate female progeny whose only source of rDNA originated from the Y-linked rDNA gene.…”

“…To investigate the impact on germline transmission, Aldrich et al crossed these male flies with females carrying an rDNA-deficient compound X chromosome to generate female progeny whose only source of rDNA originated from the Y-linked rDNA gene. This genetic strategy revealed the rDNA phenotype was transferred to female offspring, resulting in progeny with reduced rDNA copy numbers and persisted for up to two generations even though progeny were fed a standard diet (Aldrich and Maggert, 2015). The observation that the generational impact on rRNA copy number was blocked by inhibition of the TOR pathway coupled with the fact that the impact of protein-rich diet on fathers is InR-dependent implicate the insulin/TOR signaling pathway as a mechanism of germline rDNA instability (Aldrich and Maggert, 2015).…”

Linking growing up and getting old : plastic and evolutionary effects of developmental diet on adult phenotypes and gene expression in the fruit fly

“…For example, even in rapidly growing yeast cells, about 50% of the rDNA copies are silenced through epigenetic modification (Lempiäinen & Shore 2009). Intriguingly, a recent study in Drosophila found that increasing levels of dietary yeast during development lead to increased expression of ribosomal RNA genes during development and that this in turn is correlated with increased rDNA instability and loss of rDNA copies in adults (Aldrich & Maggert 2015). Furthermore, the loss of rDNA copies is known to be associated with the loss of heterochromatic induced silencing (Paredes & Maggert 2009) and the loss of heterochromatin in turn, is known to de-repress RNA synthesis and decrease lifespan in Drosophila (Larson et al 2012).…”