Computationally predicted gene regulatory networks in molluscan biomineralization identify extracellular matrix production and ion transportation pathways

Victoria A Sleight* (Corresponding Author), Philipp Antczak, Francesco Falciani, Melody S Clark

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)
7 Downloads (Pure)


The molecular processes regulating molluscan shell production remain relatively uncharacterized, despite the clear evolutionary and societal importance of biomineralization.

Here we built the first computationally predicted gene regulatory network (GRN) for molluscan biomineralization using Antarctic clam (Laternula elliptica) mantle gene expression data produced over an age-categorized shell damage-repair time-course. We used previously published in vivo in situ hybridization expression data to ground truth gene interactions predicted by the GRN and show that candidate biomineralization genes from different shell layers, and hence microstructures, were connected in unique modules. We characterized two biomineralization modules of the GRN and hypothesize that one module is responsible for translating the extracellular proteins required for growing, repairing or remodelling the nacreous shell layer, whereas the second module orchestrates the transport of both ions and proteins to the shell secretion site, which are required during normal shell growth, and repair. Our findings demonstrate that unbiased computational methods are particularly valuable for studying fundamental biological processes and gene interactions in non-model species where rich sources of gene expression data exist, but annotation rates are poor and the ability to carry out true functional tests are still lacking.

Availability and implementation
The raw RNA-Seq data is freely available for download from NCBI SRA (Accession: PRJNA398984), the assembled and annotated transcriptome can be viewed and downloaded from molluscDB ( and in addition, the assembled transcripts, reconstructed GRN, modules and detailed annotations are all available as Supplementary Files.

Supplementary information
Supplementary data are available at Bioinformatics online
Original languageEnglish
Pages (from-to)1326-1332
Number of pages7
Issue number5
Early online date16 Oct 2019
Publication statusPublished - Mar 2020

Bibliographical note

We would like to thank Prof Peter Kille for constructive comments on this work.
This work was supported by the Natural Environment Research Council Core Funding to the British Antarctic Survey, a DTG Studentship (Project Reference: NE/J500173/1) to V.A.S. and a Junior Research Fellowship to V.A.S from Wolfson College, University of Cambridge.
Conflict of Interest: none declared.


  • CLAM
  • Extracellular Matrix
  • Biomineralization
  • Ions
  • Gene Expression Profiling
  • Gene Regulatory Networks


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