BMI & ISREC Seminar // Claude Desplan: Deterministic and stochastic choices specify the large array of pheromone receptors for the social life of ants

In both flies and vertebrates, smell is perceived by olfactory sensory neurons (OSNs) that rely on the expression of a single odorant receptor (Or) gene per cell to discriminate between odors. Flies have few Or genes (~60), while mammals have many (>1,000 in mice), which is reflected in different specification mechanisms of developing OSNs in these species. The simple olfactory system of flies uses deterministic specification of cell fates by a transcription factor code, while the complex olfactory system of mammals relies on stochastic choices, including stochastic enhancer-promoter interactions, complemented by negative cross-regulation between Ors. Ants, which extensively rely on smell to navigate their physical and social milieu, lie in the middle of this spectrum. The jumping ant Harpegnathos saltator has an order of magnitude more Or genes than Drosophila melanogaster (~400). The additional genes have evolved via tandem duplications, creating large genomic arrays of Or genes positioned head-to-tail, an arrangement reminiscent of Or arrays in mammals. We investigated the expression pattern of Ors in individual OSNs in H. saltator by performing single-nucleus sequencing on the antennae. Unexpectedly, we observed that all genes in tandem Or arrays are co-expressed in a “stair step” fashion where either the most 3’ gene is expressed alone, or the two most downstream genes are co-expressed, or the last three genes are co-expressed etc. Additionally, the expression levels of multiple co-expressed genes shows a decreasing trend towards the most 3’ transcribed Or, suggesting that such co-expression may result from RNA polymerase readthrough. We propose that a single Or promoter is stochastically chosen from a cluster, activating the transcription of the corresponding gene. However, RNA polymerase fails to terminate at the end of this gene, producing long RNAs. While they include all the downstream Or sequences, those cannot be translated due to their distance from the 5’ cap. At the same time, upstream Or genes are repressed through additional mechanisms which we are currently investigating. Thus, genomic clusters of ant Ors, which have evolved to accommodate an expanded repertoire of odors related to the ants’ lifestyle, may rely on a unique mechanism to produce singular OR protein expression in each OSN.