Extensive intraspecies cryptic variation in an ancient embryonic gene regulatory network

ABSTRACTInnovations in metazoan development arise from evolutionary modification of gene regulatory networks (GRNs). We report widespread cryptic variation in the requirement for two key regulatory inputs, SKN-1/Nrf2 and MOM-2/Wnt, into the C. elegans endoderm GRN. While some natural variants show a nearly absolute requirement for these two regulators, in others, most embryos differentiate endoderm in their absence. GWAS and analysis of recombinant inbred lines reveal multiple genetic regions underlying this broad phenotypic variation. We observe a reciprocal trend, in which genomic variants, or knockdown of endoderm regulatory genes, that result in a high SKN-1 requirement often show low MOM-2/Wnt requirement and vice-versa, suggesting that cryptic variation in the endoderm GRN may be tuned by opposing requirements for these two key regulatory inputs. These findings reveal that while the downstream components in the endoderm GRN are common across metazoan phylogeny, initiating regulatory inputs are remarkably plastic even within a single species.

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Extensive intraspecies cryptic variation in an ancient embryonic gene regulatory network

eLife ◽

10.7554/elife.48220 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 12

Author(s):

Yamila N Torres Cleuren ◽

Chee Kiang Ewe ◽

Kyle C Chipman ◽

Emily R Mears ◽

Cricket G Wood ◽

...

Keyword(s):

Gene Regulatory Networks ◽

Regulatory Networks ◽

Recombinant Inbred Lines ◽

Single Species ◽

C Elegans ◽

Cryptic Variation ◽

Absolute Requirement ◽

Natural Isolates ◽

Gene Regulatory ◽

Metazoan Phylogeny

Innovations in metazoan development arise from evolutionary modification of gene regulatory networks (GRNs). We report widespread cryptic variation in the requirement for two key regulatory inputs, SKN-1/Nrf2 and MOM-2/Wnt, into the C. elegans endoderm GRN. While some natural isolates show a nearly absolute requirement for these two regulators, in others, most embryos differentiate endoderm in their absence. GWAS and analysis of recombinant inbred lines reveal multiple genetic regions underlying this broad phenotypic variation. We observe a reciprocal trend, in which genomic variants, or knockdown of endoderm regulatory genes, that result in a high SKN-1 requirement often show low MOM-2/Wnt requirement and vice-versa, suggesting that cryptic variation in the endoderm GRN may be tuned by opposing requirements for these two key regulatory inputs. These findings reveal that while the downstream components in the endoderm GRN are common across metazoan phylogeny, initiating regulatory inputs are remarkably plastic even within a single species.

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Integration of Metabolic and Gene Regulatory Networks Modulates the C. elegans Dietary Response

Cell ◽

10.1016/j.cell.2013.05.022 ◽

2013 ◽

Vol 153 (6) ◽

pp. 1406-1407

Author(s):

Emma Watson ◽

Lesley T. MacNeil ◽

H. Efsun Arda ◽

Lihua Julie Zhu ◽

Albertha J.M. Walhout

Keyword(s):

Gene Regulatory Networks ◽

Regulatory Networks ◽

C Elegans ◽

Gene Regulatory

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Natural cryptic variation in epigenetic modulation of an embryonic gene regulatory network

10.1101/831099 ◽

2019 ◽

Author(s):

Chee Kiang Ewe ◽

Yamila N. Torres Cleuren ◽

Sagen E. Flowers ◽

Geneva Alok ◽

Russell G. Snell ◽

...

Keyword(s):

Regulatory Networks ◽

Phenotypic Diversity ◽

Epigenetic Modification ◽

Genomic Variation ◽

Bzip Transcription Factor ◽

Rnai Pathway ◽

C Elegans ◽

Cryptic Variation ◽

Organ Systems ◽

Gene Regulatory

AbstractGene regulatory networks (GRNs) that direct animal embryogenesis must respond to varying environmental and physiological conditions to ensure robust construction of organ systems. While GRNs are evolutionarily modified by natural genomic variation, the roles of epigenetic processes in shaping plasticity of GRN architecture are not well-understood. The endoderm GRN in C. elegans is initiated by the maternally supplied SKN-1/Nrf2 bZIP transcription factor; however, the requirement for SKN-1 in endoderm specification varies widely among distinct C. elegans wild isotypes owing to rapid developmental system drift driven by accumulation of cryptic genetic variants. We report here that heritable epigenetic factors that are stimulated by transient developmental diapause also underlie cryptic variation in the requirement for SKN-1 in endoderm development. This epigenetic memory is inherited from the maternal germline, apparently through a nuclear, rather than cytoplasmic, signal, resulting in a parent-of-origin effect (POE), in which the phenotype of the progeny resembles that of the maternal founder. The occurrence and persistence of POE varies between different parental pairs, perduring for at least ten generations in one pair. This long-perduring POE requires piwi-piRNA function and the germline nuclear RNAi pathway, as well as MET-2 and SET-32, which direct histone H3K9 trimethylation and drive heritable epigenetic modification. Such non-genetic cryptic variation may provide a resource of additional phenotypic diversity through which adaptation may facilitate evolutionary changes and shape developmental regulatory systems.

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Integration of Metabolic and Gene Regulatory Networks Modulates the C. elegans Dietary Response

Cell ◽

10.1016/j.cell.2013.02.050 ◽

2013 ◽

Vol 153 (1) ◽

pp. 253-266 ◽

Cited By ~ 82

Author(s):

Emma Watson ◽

Lesley T. MacNeil ◽

H. Efsun Arda ◽

Lihua Julie Zhu ◽

Albertha J.M. Walhout

Keyword(s):

Gene Regulatory Networks ◽

Regulatory Networks ◽

C Elegans ◽

Gene Regulatory

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The Nature, Extent, and Consequences of Cryptic Genetic Variation in the opa Repeats of Notch in Drosophila

10.1101/020529 ◽

2015 ◽

Cited By ~ 1

Author(s):

Clinton Rice ◽

Danielle Beekman ◽

Liping Liu ◽

Albert Erives

Keyword(s):

Gene Regulatory Networks ◽

Self Assembly ◽

Regulatory Networks ◽

Sanger Sequencing ◽

Rare Allele ◽

Wild Type ◽

Cryptic Variation ◽

Rare Alleles ◽

Long Read ◽

Gene Regulatory

Polyglutamine (pQ) tracts are abundant in many proteins co-interacting on DNA. The lengths of these pQ tracts can modulate their interaction strengths. However, pQ tracts > 40 residues are pathologically prone to amyloidogenic self-assembly. Here, we assess the extent and consequences of variation in the pQ-encoding opa repeats of Notch (N) in Drosophila melanogaster. We use Sanger sequencing to genotype opa sequences (5'-CAX repeats), which have resisted assembly using short sequence reads. While the majority of N sequences pertain to reference opa31 (Q13HQ17) and opa32 (Q13HQ18) allelic classes, several rare alleles encode tracts > 32 residues: opa33a (Q14HQ18), opa33b (Q15HQ17), opa34 (Q16HQ17), opa35a1/opa35a2 (Q13HQ21), opa36 (Q13HQ22), and opa37 (Q13HQ23). Only one rare allele encodes a tract < 31 residues: opa23 (Q13-Q10). This opa23 allele shortens the pQ tract while simultaneously eliminating the interrupting histidine. Homozygotes for the short and long opa alleles have defects in sensory bristle organ specification, abdominal patterning, and embryonic survival. Inbred stocks with wild-type opa31 alleles become more viable when outbred, while an inbred stock with the longer opa35 becomes less viable after outcrossing to different backgrounds. In contrast, an inbred stock with the short opa23 allele is semi-viable in both inbred and outbred genetic backgrounds. This opa23 Notch allele also produces notched wings when recombined out of the X chromosome. Importantly, w[apricot]-linked X balancers carry the N allele opa33b and suppress AS-C insufficiency caused by the sc8 inversion. Our results demonstrate significant cryptic variation and epistatic sensitivity for the N locus, and the need for long read genotyping of key repeat variables underlying gene regulatory networks.

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