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Table S1, S2 and Figures S1, S2, S3 and S4

The coevolution between dispersal and sociality can lead to linked polymorphisms in both traits, which may favour the emergence of supergenes. Supergenes have recently been found to control social organization in several ant lineages. Whether and how these ‘social supergenes’ also control traits related to dispersal is yet unknown. Our goal here was to get a comprehensive view of the dispersal mechanisms associated with supergene-controlled alternative social forms in the ant Formica selysi. We measured the production and emission of young females and males by single-queen (monogyne) and multiple-queen (polygyne) colonies, the composition of mating aggregations, and the frequency of crosses within and between social forms in the wild. We found that males and females from alternative social forms did not display strong differences in their propensity to leave the nest and disperse, nor in their mating behaviour. Instead, the social forms differed substantially in sex allocation. Monogyne colonies produced 90% of the females flying to swarms, whereas 57% of the males in swarms originated from polygyne colonies. Most crosses were assortative with respect to social form. However, 20% of the monogyne females did mate with polygyne males, which is surprising as this cross has never been found in mature monogyne colonies. We suggest that the polygyny-determining haplotype free rides on monogyne females, who establish independent colonies that later become polygyne. By identifying the steps in dispersal where the social forms differ, this study sheds light on the behavioural and colony-level traits linking dispersal and sociality through supergenes.

Transposable elements (TEs) account for more than 50% of the human genome and many have been co-opted throughout evolution to provide regulatory functions for gene expression networks. Several lines of evidence suggest that these networks are fine-tuned by the largest family of TE controllers, the KRAB-containing zinc finger proteins (KZFPs). One tissue permissive for TE transcriptional activation (termed “transposcription”) is the adult human brain, however comprehensive studies on the extent of this process and its potential contribution to human brain development are lacking. To elucidate the spatiotemporal transposcriptome of the developing human brain, we have analyzed two independent RNA-seq data sets encompassing 16 brain regions from eight weeks postconception into adulthood. We reveal a distinct KZFP:TE transcriptional profile defining the late prenatal to early postnatal transition, and the spatiotemporal and cell type–specific activation of TE-derived alternative promoters driving the expression of neurogenesis-associated genes. Long-read sequencing confirmed these TE-driven isoforms as significant contributors to neurogenic transcripts. We also show experimentally that a co-opted antisense L2 element drives temporal protein relocalization away from the endoplasmic reticulum, suggestive of novel TE dependent protein function in primate evolution. This work highlights the widespread dynamic nature of the spatiotemporal KZFP:TE transcriptome and its importance throughout TE mediated genome innovation and neurotypical human brain development. To facilitate interactive exploration of these spatiotemporal gene and TE expression dynamics, we provide the “Brain TExplorer” web application freely accessible for the community.

The human genome contains some 4 million transposable element (TE)-derived sequences, which collectively influence gene expression from early embryogenesis to adulthood. The illegitimate production of oncogene-encoding TE-driven transpochimeric gene transcripts (TcGTs) has been noted in tumors, but their participation in the oncogenic process has seldom been demonstrated. Here we describe how the aberrant de-repression of a primate-specific LTR66 endogenous retroviral promoter generates a TcGT overexpressing the great-ape-restricted POU5F1B retrogene in ~65% of 286 colorectal cancers (CRC) patients, correlating with more advanced tumor stages and shorter relapse-free and overall survival. We further demonstrate that the POU5F1B protein stimulates the clonogenic and proliferation capacity of human CRC cell lines in vitro, and their tumorigenic and metastatic potential in mouse xenotransplantation models. Although POU5F1B is a retrotransposition-mediated derivative of the POU5F1/OCT4 transcription factor, its product is a predominantly cytoplasmic protein enriched in membranes that associates with mediators of signal transduction, notably the ERBB2 receptor tyrosine kinase and several of its known interactors. POU5F1B overexpression results in activating genes involved in signaling, and conditioned medium of POU5F1B-overexpressing cells enhances the clonogenic potential of CRC cells in trans. As POU5F1B is encoded by an apparently non-essential gene only lowly expressed in normal tissues, and as POU5F1B-containing TcGTs are detected in other tumors besides CRC, it represents an attractive target for the development of cancer therapies. Citation Format: Laia Simó-Riudalbas, Evarist Planet, Sandra Offner, Julien Duc, Laurence Abrami, Sagane Dind, Alexandre Coudray, Mairene Coto-Llerena, Salvatore Piscuoglio, Claus L. Andersen, Jesper Bertram Bramsen, Didier Trono. Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2853.