Widespread transposon co-option in the Caenorhabditis germline regulatory network

Abstract

The movement of selfish DNA elements can lead to widespread genomic alterations with potential to create novel functions. We show that transposon expansions in Caenorhabditis nematodes led to extensive rewiring of germline transcriptional regulation. We find that about one-third of Caenorhabditis elegans germline-specific promoters have been co-opted from two related miniature inverted repeat transposable elements (TEs), CERP2 and CELE2. These promoters are regulated by HIM-17, a THAP domain-containing transcription factor related to a transposase. Expansion of CERP2 occurred before radiation of the Caenorhabditis genus, as did fixation of mutations in HIM-17 through positive selection, whereas CELE2 expanded only in C. elegans. Through comparative analyses in Caenorhabditis briggsae, we find not only evolutionary conservation of most CERP2 co-opted promoters but also a substantial fraction that are species-specific. Our work reveals the emergence and evolutionary conservation of a novel transcriptional network driven by TE co-option with a major impact on regulatory evolution.

Fig. 1.. TE enrichment at germline-specific elements in C. elegans.

(A) Example of germline-specific (purple) promoter in C. elegans. (B) Sequence logos of the m1 and m2 motifs. (C) Number of m1m2 pairs overlapping germline-specific promoters, color-coded based on their relative orientation. (D) Location of m1m2 pairs in CERP2 and CELE2 consensus. IR, inverted repeat. (E) Green fluorescent protein (GFP) and 4′,6-diamidino-2-phenylindole (DAPI) signals from CERP2-derived wild-type (wt) p(C16A11.4)::his-58::gfp and m1m2-scrambled p(C16A11.4)::his-58::gfp in adult gonads. Scale bars, 20 μm.

Fig. 2.. HIM-17 binds and regulates co-opted MITEs.

(A) Example of HIM-17 ChIP-seq binding profile. (B) Fraction of promoters overlapped by HIM-17 peaks. (C) Genome-wide overlap between HIM-17 peaks and m1m2 pairs. (D) Example of a gene down-regulated specifically in him-17 mutants. (E) Gene Ontology (GO) term enrichment of HIM-17 down-regulated direct targets regulated by a co-opted promoter.

Fig. 3.. Evolution of m1m2 pairs and their binding factor in nematodes.

(A and B) Number of CERP2 (A) and CELE2 (B) elements annotated in the genomes of different nematode species, and fraction of divergent m1m2 pairs, tandem m2 m1+ pairs, and other m1 and or m2 motifs overlapped. (C) Evolutionary conservation of him-17. (D) Top: Location of sites under positive selection with respect to the C. elegans HIM-17 protein. In dark, sites located in a THAP domain. Bottom: Location of THAP domains in HIM-17 orthologs. Color code reflects their similarity to the canonical THAP domain (based on the hmmsearch score). Second and fourth THAP domains are highlighted in gray. Protein length is drawn to scale and truncated for longer orthologs.

Fig. 4.. Evolutionary conservation and turnover of co-opted MITEs.

(A) phyloP score profile (top) and heatmap (bottom) measured at germline-specific promoters associated to a divergent m1m2 pair in C. elegans. Elements not aligned to other species were removed from the heatmap. (B) Number of germline-specific promoters annotated in C. elegans and C. briggsae. (C and D) Examples of orthologs with a germline-specific CERP2-derived promoter in C. elegans conserved in C. briggsae (C) or C. elegans specific (D).