Transposable elements and their KZFP controllers are drivers of transcriptional innovation in the developing human brain.

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.

Disentangling the mechanisms linking dispersal and sociality in supergene-mediated ant social forms.

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.

Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis.

The treatment of colorectal cancer (CRC) is an unmet medical need in absence of early diagnosis. Here, upon characterizing cancer-specific transposable element-driven transpochimeric gene transcripts (TcGTs) produced by this tumor in the SYSCOL cohort, we find that expression of the hominid-restricted retrogene POU5F1B through aberrant activation of a primate-specific endogenous retroviral promoter is a strong negative prognostic biomarker. Correlating this observation, we demonstrate that POU5F1B fosters the proliferation and metastatic potential of CRC cells. We further determine that POU5F1B, in spite of its phylogenetic relationship with the POU5F1/OCT4 transcription factor, is a membrane-enriched protein that associates with protein kinases and known targets or interactors as well as with cytoskeleton-related molecules, and induces intracellular signaling events and the release of trans-acting factors involved in cell growth and cell adhesion. As POU5F1B is an apparently non-essential gene only lowly expressed in normal tissues, and as POU5F1B-containing TcGTs are detected in other tumors besides CRC, our data provide interesting leads for the development of cancer therapies.