Hanchate, N. K. et al. Single-cell transcriptomics reveals receptor transformations during olfactory neurogenesis. Science 350, 1251–1255 (2015).
Tan, L., Li, Q. & Xie, X. S. Olfactory sensory neurons transiently express multiple olfactory receptors during development. Mol. Syst. Biol. 11, 844 (2015).
Fuss, S. H. & Ray, A. Mechanisms of odorant receptor gene choice in Drosophila and vertebrates. Mol. Cell. Neurosci. 41, 101–112 (2009).
Barnes, I. H. A. et al. Expert curation of the human and mouse olfactory receptor gene repertoires identifies conserved coding regions split across two exons. BMC Genom. 21, 196 (2020).
Ressler, K. J., Sullivan, S. L. & Buck, L. B. A zonal organization of odorant receptor gene expression in the olfactory epithelium. Cell 73, 597–609 (1993).
Markenscoff-Papadimitriou, E. et al. Enhancer interaction networks as a means for singular olfactory receptor expression. Cell 159, 543–557 (2014).
Dalton, R. P., Lyons, D. B. & Lomvardas, S. Co-opting the unfolded protein response to elicit olfactory receptor feedback. Cell 155, 321–332 (2013).
Pourmorady, A. D. et al. RNA-mediated symmetry breaking enables singular olfactory receptor choice. Nature 625, 181–188 (2024).
Dalton, R. P. & Lomvardas, S. Chemosensory receptor specificity and regulation. Annu. Rev. Neurosci. 38, 331–349 (2015).
Vosshall, L. B., Amrein, H., Morozov, P. S., Rzhetsky, A. & Axel, R. A spatial map of olfactory receptor expression in the Drosophila antenna. Cell 96, 725–736 (1999).
McLaughlin, C. N. et al. Single-cell transcriptomes of developing and adult olfactory receptor neurons in Drosophila. eLife 10, e63856 (2021).
Mermet, J. et al. Multilayer regulation underlies the functional precision and evolvability of the olfactory system. Preprint at bioRxiv https://doi.org/10.1101/2025.01.16.632932 (2025).
Tichy, A. L., Ray, A. & Carlson, J. R. A new Drosophila POU gene, pdm3, acts in odor receptor expression and axon targeting of olfactory neurons. J. Neurosci. 28, 7121–7129 (2008).
Clyne, P. J. et al. A novel family of divergent seven-transmembrane proteins: candidate odorant receptors in Drosophila. Neuron 22, 327–338 (1999).
Li, Q. et al. A functionally conserved gene regulatory network module governing olfactory neuron diversity. PLoS Genet. 12, e1005780 (2016).
Endo, K., Aoki, T., Yoda, Y., Kimura, K.-I. & Hama, C. Notch signal organizes the Drosophila olfactory circuitry by diversifying the sensory neuronal lineages. Nat. Neurosci. 10, 153–160 (2007).
Ray, A., van Naters, W., van der, G., Shiraiwa, T. & Carlson, J. R. Mechanisms of odor receptor gene choice in Drosophila. Neuron 53, 353–369 (2007).
Yan, H. et al. An engineered orco mutation produces aberrant social behavior and defective neural development in ants. Cell 170, 736–747 (2017).
Zhou, X. et al. Phylogenetic and transcriptomic analysis of chemosensory receptors in a pair of divergent ant species reveals sex-specific signatures of odor coding. PLoS Genet. 8, e1002930 (2012).
McKenzie, S. K. & Kronauer, D. J. C. The genomic architecture and molecular evolution of ant odorant receptors. Genome Res. 28, 1757–1765 (2018).
Pask, G. M. et al. Specialized odorant receptors in social insects that detect cuticular hydrocarbon cues and candidate pheromones. Nat. Commun. 8, 297 (2017).
Slone, J. D. et al. Functional characterization of odorant receptors in the ponerine ant, Harpegnathos saltator. Proc. Natl Acad. Sci. USA 114, 8586–8591 (2017).
Brahma, A. et al. Transcriptional and post-transcriptional control of odorant receptor choice in ants. Curr. Biol. 33, 5456–5466 (2023).
Sieriebriennikov, B. et al. Orco-dependent survival of odorant receptor neurons in ants. Sci. Adv. 10, eadk9000 (2024).
Mika, K. et al. Olfactory receptor-dependent receptor repression in Drosophila. Sci. Adv. 7, eabe3745 (2021).
Gruber, A. J. et al. A comprehensive analysis of 3’ end sequencing data sets reveals novel polyadenylation signals and the repressive role of heterogeneous ribonucleoprotein C on cleavage and polyadenylation. Genome Res. 26, 1145–1159 (2016).
Zeng, Y., Zhang, H.-W., Wu, X.-X. & Zhang, Y. Structural basis of exoribonuclease-mediated mRNA transcription termination. Nature 628, 887–893 (2024).
Proudfoot, N. J. Transcriptional termination in mammals: stopping the RNA polymerase II juggernaut. Science 352, aad9926 (2016).
Calvo-Roitberg, E. et al. Challenges in identifying mRNA transcript starts and ends from long-read sequencing data. Genome Res. 34, 1719–1734 (2024).
Ohler, U., Liao, G.-C., Niemann, H. & Rubin, G. M. Computational analysis of core promoters in the Drosophila genome. Genome Biol. 3, R87 (2002).
FitzGerald, P. C., Sturgill, D., Shyakhtenko, A., Oliver, B. & Vinson, C. Comparative genomics of Drosophila and human core promoters. Genome Biol. 7, R53 (2006).
Vo Ngoc, L., Cassidy, C. J., Huang, C. Y., Duttke, S. H. C. & Kadonaga, J. T. The human initiator is a distinct and abundant element that is precisely positioned in focused core promoters. Genes Dev. 31, 6–11 (2017).
Neri, F. et al. Intragenic DNA methylation prevents spurious transcription initiation. Nature 543, 72–77 (2017).
Sieriebriennikov, B., Reinberg, D. & Desplan, C. A molecular toolkit for superorganisms. Trends Genet. 37, 846–859 (2021).
Greger, I. H. & Proudfoot, N. J. Poly(A) signals control both transcriptional termination and initiation between the tandem GAL10 and GAL7 genes of Saccharomyces cerevisiae. EMBO J. 17, 4771–4779 (1998).
Hainer, S. J., Pruneski, J. A., Mitchell, R. D., Monteverde, R. M. & Martens, J. A. Intergenic transcription causes repression by directing nucleosome assembly. Genes Dev. 25, 29–40 (2011).
Greger, I. H., Aranda, A. & Proudfoot, N. Balancing transcriptional interference and initiation on the GAL7 promoter of Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 97, 8415–8420 (2000).
Tsompana, M. & Buck, M. J. Chromatin accessibility: a window into the genome. Epigenet. Chromatin 7, 33 (2014).
Makalowska, I., Lin, C.-F. & Makalowski, W. Overlapping genes in vertebrate genomes. Comput. Biol. Chem. 29, 1–12 (2005).
Rosa, S., Duncan, S. & Dean, C. Mutually exclusive sense–antisense transcription at FLC facilitates environmentally induced gene repression. Nat. Commun. 7, 13031 (2016).
Kiefer, L. et al. WAPL functions as a rheostat of protocadherin isoform diversity that controls neural wiring. Science 380, eadf8440 (2023).
Canzio, D. et al. Antisense lncRNA transcription mediates DNA demethylation to drive stochastic protocadherin α promoter choice. Cell 177, 639–653 (2019).
Hobson, D. J., Wei, W., Steinmetz, L. M. & Svejstrup, J. Q. RNA polymerase II collision interrupts convergent transcription. Mol. Cell 48, 365–374 (2012).
Zhang, W. et al. Evolutionary process underlying receptor gene expansion and cellular divergence of olfactory sensory neurons in honeybees. Mol. Biol. Evol. 42, msaf080 (2025).
Prieto-Godino, L. L. et al. Evolution of acid-sensing olfactory circuits in drosophilids. Neuron 93, 661–676 (2017).
Chen, Y.-C. A. et al. Cutoff suppresses RNA polymerase II termination to ensure expression of piRNA precursors. Mol. Cell 63, 97–109 (2016).
Sieber, K. et al. Embryo injections for CRISPR-mediated mutagenesis in the ant Harpegnathos saltator. J. Vis. Exp. https://doi.org/10.3791/61930 (2021).
Addo-Quaye, C., Eshoo, T. W., Bartel, D. P. & Axtell, M. J. Endogenous siRNA and miRNA targets identified by sequencing of the Arabidopsis degradome. Curr. Biol. 18, 758–762 (2008).
Wang, W. et al. The initial uridine of primary piRNAs does not create the tenth adenine that Is the hallmark of secondary piRNAs. Mol. Cell 56, 708–716 (2014).
Kim, H. et al. Bias-minimized quantification of microRNA reveals widespread alternative processing and 3’ end modification. Nucleic Acids Res. 47, 2630–2640 (2019).
Fu, Y., Wu, P.-H., Beane, T., Zamore, P. D. & Weng, Z. Elimination of PCR duplicates in RNA-seq and small RNA-seq using unique molecular identifiers. BMC Genom. 19, 531 (2018).
Ibrahim, F., Oppelt, J., Maragkakis, M. & Mourelatos, Z. TERA-seq: true end-to-end sequencing of native RNA molecules for transcriptome characterization. Nucleic Acids Res. 49, e115 (2021).
Liu, N. et al. Direct promoter repression by BCL11A controls the fetal to adult hemoglobin switch. Cell 173, 430–442 (2018).
Niimura, Y. & Nei, M. Comparative evolutionary analysis of olfactory receptor gene clusters between humans and mice. Gene 346, 13–21 (2005).
Shields, E. J., Sheng, L., Weiner, A. K., Garcia, B. A. & Bonasio, R. High-quality genome assemblies reveal long non-coding RNAs expressed in ant brains. Cell Rep. 23, 3078–3090 (2018).
Gomez-Diaz, C., Martin, F., Garcia-Fernandez, J. M. & Alcorta, E. The two main olfactory receptor families in Drosophila, ORs and IRs: acomparative approach. Front. Cell. Neurosci. 12, 253 (2018).
Satpathy, A. T. et al. Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion. Nat. Biotechnol. 37, 925–936 (2019).
Zheng, G. X. Y. et al. Massively parallel digital transcriptional profiling of single cells. Nat. Commun. 8, 14049 (2017).
Wolf, F. A., Angerer, P. & Theis, F. J. SCANPY: large-scale single-cell gene expression data analysis. Genome Biol. 19, 15 (2018).
Gayoso, A. et al. A Python library for probabilistic analysis of single-cell omics data. Nat. Biotechnol. 40, 163–166 (2022).
Li, H. et al. Fly Cell Atlas: a single-nucleus transcriptomic atlas of the adult fruit fly. Science 375, eabk2432 (2022).
Virtanen, P. et al. SciPy 1.0: fundamental algorithms for scientific computing in Python. Nat. Methods 17, 261–272 (2020).
Seabold, S. & Perktold, J. Statsmodels: econometric and statistical modeling with Python. In Proc. Python in Science Conference (eds van der Walt, S. & Millman, J.) 92–96 (SciPy, 2010).
Gospocic, J. et al. Kr-h1 maintains distinct caste-specific neurotranscriptomes in response to socially regulated hormones. Cell 184, 5807–5823 (2021).
Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).
Li, H. New strategies to improve minimap2 alignment accuracy. Bioinformatics 37, 4572–4574 (2021).
Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).
Ramírez, F. et al. deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 44, W160–W165 (2016).
Bailey, T. L., Johnson, J., Grant, C. E. & Noble, W. S. The MEME Suite. Nucleic Acids Res. 43, W39–W49 (2015).
Vasimuddin, M., Misra, S., Li, H. & Aluru, S. Efficient architecture-aware acceleration of BWA-MEM for multicore systems. In Proc. 2019 IEEE International Parallel and Distributed Processing Symposium (IPDPS) 314–324 (IEEE, 2019).
Hoskins, R. A. et al. Genome-wide analysis of promoter architecture in Drosophila melanogaster. Genome Res. 21, 182–192 (2011).
Waterhouse, A. M., Procter, J. B., Martin, D. M. A., Clamp, M. & Barton, G. J. Jalview version 2—a multiple sequence alignment editor and analysis workbench. Bioinformatics 25, 1189–1191 (2009).
