DnaJ chaperones contribute to canalization

Abstract

Canalization, an intrinsic robustness of development to external (environmental) or internal (genetic) perturbations, was first proposed over half a century ago. However, whether the robustness to environmental stress (environmental canalization [EC]) and to genetic variation (genetic canalization) are underpinned by the same molecular basis remains elusive. The recent discovery of the involvement of two endoplasmic reticulum (ER)‐associated DnaJ genes in developmental buffering, orthologues of which are conserved across Metazoa, indicates that the role of ER‐associated DnaJ genes might be conserved across the animal kingdom. To test this, we surveyed the ER‐associated DnaJ chaperones in the nematode Caenorhabditis elegans. We then quantified the phenotype, in the form of variance and mean of seam cell counts, from RNA interference knockdown of DnaJs under three different temperatures. We find that seven out of eight ER‐associated DnaJs are involved in either EC or microenvironmental canalization. Moreover, we also found two DnaJ genes not specifically associated with ER (DNAJC2/dnj‐11 and DNAJA2/dnj‐19) were involved in canalization. Protein expression pattern showed that these DnaJs are upregulated by heat stress, yet not all of them are expressed in the seam cells. Moreover, we found that most of the buffering DnaJs also control lifespan. We therefore concluded that a number of DnaJ chaperones, not limited to those associated with the ER, are involved in canalization as a part of the complex system that underlies development.

Co-expression network analysis of environmental canalization in the ascidian Ciona

“…Supporting this, the 15 MDBGs include genes involved in the cell cycle (KY.Chr2.1529, Leucine aminopeptidase 3 (LAP3)), translation, stress response (KY.Chr2.2295, catalase), degradation in homeostasis (KY.Chr6.691, glycosylated lysosomal membrane protein (GLMP)), innate immunity (KY.Chr14.407; interferon regulatory factor 2 (IRF2)) and metabolism (Chr2.1046; galactocerebrosidase; KY.Chr9.550, speedy protein; Chr7.688, serine protease 27 (PRSS27)), while we did not find any transcription factors that are involved in development (Additional file 2: Table S4). We note that one of the other MDBGs, DnaJC10, was previously shown to be involved in canalization [6,7].…”

“…The idea of environmental canalization has been a matter of debate over the past half a century. In addition to chaperone proteins [2][3][4][5][6][7], various other molecules and potential mechanisms have been identified as relevant to environmental canalization (see reviews, [8][9][10]). Other studies suggested that canalization is a property of gene networks [11][12][13].…”

Genes for Yield Stability in Tomatoes

“…Similarly, a C. elegans study showed that seven of eight endoplasmic reticulum associated DNAJ genes are involved in trait canalization. [ 20 ] It is important to note that an independent allele at the same locus ( ghost‐2 ), as well as two CRISPR/CAS9‐generated mutations had leaf variegation but did not exhibit the unstable variegation phenotype. ghost‐2 produced uniformly large plants and the CRISPR/CAS9 mutants did not survive beyond the first true leaf stage.…”

Cryptic genetic variation in a heat shock protein modifies the outcome of a mutation affecting epidermal stem cell development in C. elegans

“…Hsp-90-mediated buffering of protein folding has been thought to influence the variable expressivity of human disease 56 . In the seam, RNAi knockdown of hsp-90 or DnaJ chaperones leads to increased variability in SCN 10 , 57 . Differences in heat shock protein expression have also been shown to affect the incomplete penetrance of mutations 23 , 58 .…”