No Transcriptional Compensation for Extreme Gene Dosage Imbalance in Fragmented Bacterial Endosymbionts of Cicadas

Abstract

AbstractBacteria that form long-term intracellular associations with host cells lose many genes, a process that often results in tiny, gene-dense, and stable genomes. Paradoxically, the same evolutionary processes that drive genome reduction and simplification may also sometimes cause genome expansion and complexification. A bacterial endosymbiont of cicadas,Hodgkinia cicadicola, exemplifies this paradox. In many cicada species, a singleHodgkinialineage with a tiny, gene-dense genome has split into several interdependent cell and genome lineages. Each newHodgkinialineage encodes a unique subset of the ancestral unsplit genome in a complementary way, such that the collective gene contents of all lineages sum to the total found in the ancestral single genome. This splitting process creates genetically distinctHodgkiniacells that must function together to carry out basic cellular processes, but also creates a gene dosage problem where some genes are encoded by only a small fraction of cells while others are much more abundant. Here, by sequencing DNA and RNA ofHodgkiniafrom different cicada species with different amounts of splitting – along with those of its structurally stable, unsplit partner endosymbiontSulcia muelleri– we show thatHodgkiniadoes not transcriptionally compensate to rescue the wildly unbalanced gene and genome ratios that result from lineage splitting. We also find evidence thatHodgkiniahas a reduced capacity for basic transcriptional control independent of the splitting process. Collectively, these findings reveal another layer of degeneration that further pushes the limits of canonical molecular and cell biology inHodgkinia, and may in part explain its propensity to go extinct through symbiont replacement.SignificanceMany cicadas host two bacterial endosymbionts,HodgkiniaandSulcia, which produce essential amino acids missing from the insect’s xylem sap diet. Following 100+ million years of strict host association, both bacteria have lost many genes and posses extremely tiny genomes. In some cicadas,Hodgkiniahas split into multiple cell lineages, distributing its genes, with little respect to their function, among separate lineages present at (sometimes wildly) different abundances. We find no transcriptional response to this inHodgkinia, resulting in similarly imbalanced mRNA abundances. We also find less control of transcription inHodgkiniacompared toSulcia.Hodgkinia’s transcriptome embodies an extreme, even relative to other highly-reduced endosymbionts, and raises questions about how cell biology in multi-lineageHodgkiniacan function at all.