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Cortex cis-regulatory switches establish scale colour identity and pattern diversity in Heliconius.

ABSTRACT: In Heliconius butterflies, wing colour pattern diversity and scale types are controlled by a few genes of large effect that regulate colour pattern switches between morphs and species across a large mimetic radiation. One of these genes, cortex, has been repeatedly associated with colour pattern evolution in butterflies. Here we carried out CRISPR knockouts in multiple Heliconius species and show that cortex is a major determinant of scale cell identity. Chromatin accessibility profiling and introgression scans identified cis-regulatory regions associated with discrete phenotypic switches. CRISPR perturbation of these regions in black hindwing genotypes recreated a yellow bar, revealing their spatially limited activity. In the H. melpomene/timareta lineage, the candidate CRE from yellow-barred phenotype morphs is interrupted by a transposable element, suggesting that cis-regulatory structural variation underlies these mimetic adaptations. Our work shows that cortex functionally controls scale colour fate and that its cis-regulatory regions control a phenotypic switch in a modular and pattern-specific fashion.

SUBMITTER: Livraghi L

PROVIDER: S-EPMC8289415 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMany studies report about detection and functional characterization of cis-regulatory motifs in untranslated regions (UTRs) of mRNAs but little is known about the nature and functional role of their distribution. To address this issue we have developed a computational approach based on the use of data mining techniques. The idea is that of mining frequent combinations of translation regulatory motifs, since their significant co-occurrences could reveal functional relationships important for the post-transcriptional control of gene expression. The experimentation has been focused on targeted mitochondrial transcripts to elucidate the role of translational control in mitochondrial biogenesis and function.ResultsThe analysis is based on a two-stepped procedure using a sequential pattern mining algorithm. The first step searches for frequent patterns (FPs) of motifs without taking into account their spatial displacement. In the second step, frequent sequential patterns (FSPs) of spaced motifs are generated by taking into account the conservation of spacers between each ordered pair of co-occurring motifs. The algorithm makes no assumption on the relation among motifs and on the number of motifs involved in a pattern. Different FSPs can be found depending on different combinations of two parameters, i.e. the threshold of the minimum percentage of sequences supporting the pattern, and the granularity of spacer discretization. Results can be retrieved at the UTRminer web site: http://utrminer.ba.itb.cnr.it/. The discovered FPs of motifs amount to 216 in the overall dataset and to 140 in the human subset. For each FP, the system provides information on the discovered FSPs, if any. A variety of search options help users in browsing the web resource. The list of sequence IDs supporting each pattern can be used for the retrieval of information from the UTRminer database.ConclusionComputational prediction of structural properties of regulatory sequences is not trivial. The presented data mining approach is able to overcome some limits observed in other competitive tools. Preliminary results on UTR sequences from nuclear transcripts targeting mitochondria are promising and lead us to be confident on the effectiveness of the approach for future developments.

Project description:BackgroundCryptosporidium parvum is a unicellular eukaryote in the phylum Apicomplexa. It is an obligate intracellular parasite that causes diarrhea and is a significant AIDS-related pathogen. Cryptosporidium parvum is not amenable to long-term laboratory cultivation or classical molecular genetic analysis. The parasite exhibits a complex life cycle, a broad host range, and fundamental mechanisms of gene regulation remain unknown. We have used data from the recently sequenced genome of this organism to uncover clues about gene regulation in C. parvum. We have applied two pattern finding algorithms MEME and AlignACE to identify conserved, over-represented motifs in the 5' upstream regions of genes in C. parvum. To support our findings, we have established comparative real-time -PCR expression profiles for the groups of genes examined computationally.ResultsWe find that groups of genes that share a function or belong to a common pathway share upstream motifs. Different motifs are conserved upstream of different groups of genes. Comparative real-time PCR studies show co-expression of genes within each group (in sub-sets) during the life cycle of the parasite, suggesting co-regulation of these genes may be driven by the use of conserved upstream motifs.ConclusionThis is one of the first attempts to characterize cis-regulatory elements in the absence of any previously characterized elements and with very limited expression data (seven genes only). Using de novo pattern finding algorithms, we have identified specific DNA motifs that are conserved upstream of genes belonging to the same metabolic pathway or gene family. We have demonstrated the co-expression of these genes (often in subsets) using comparative real-time-PCR experiments thus establishing evidence for these conserved motifs as putative cis-regulatory elements. Given the lack of prior information concerning expression patterns and organization of promoters in C. parvum we present one of the first investigations of gene regulation in this important human pathogen.

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Cortex cis-regulatory switches establish scale colour identity and pattern diversity in Heliconius.

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