bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.07.10.737832

A developmental chimera: co-option of appendage, secretory and myogenic programs underlies spider venom gland evolution

Zancolli, G.·Hassan, A.·McGregor, A. P.·Moran, Y.·Robinson-Rechavi, M.
View original source ↗Export metadata ↓

Abstract

The evolutionary emergence of complex organs requires the integration of distinct developmental modules, yet the mechanisms bridging divergent tissue programs into unified functional units remain poorly understood. Animal venom systems, combining high-output secretory epithelia with muscular delivery systems, a provide an exceptional model for studying this modular integration. Here, we show that the venom gland of the spider Parasteatoda tepidariorum is a developmental chimera built by the hierarchical co-option of three ancestral programs. The appendage-patterning gene Distal-less establishes the primary spatial coordinate system for gland development. Downstream, the transcription factor sage maintains secretory epithelium identity; its loss causes downregulation of key venom-processing enzymes and triggers a dramatic phenotypic reversion to a neuronal state. This neural upregulation, accompanied by the downregulation of Notch ligands (delta and jagged), reveals that sage actively represses a latent neural program to maintain secretory fate. Crucially, the myogenic factor sum-1 governs the surrounding muscle layer to drive paracrine crosstalk (Wnt) and sustain lipid metabolism. Knockdown of sum-1 downregulates wntless and fatty acid anabolism genes, alongside the abnormal accumulation of lipid droplets in the secretory epithelium. Ultimately, our findings demonstrate how a complex organ is assembled by fusing an appendicular address, a repressed neuroglandular program, and a myogenic metabolic driver. This modular architecture illustrates a fundamental principle in evolutionary developmental biology: novelty can arise by harnessing the physiological and metabolic capacities of adjacent tissues to fuel the physiological demands of a newly emerged organ. Significance statementHow novel organs evolve by integrating distinct developmental modules remains a fundamental question in biology. Using the spider venom gland as a model, we show that this complex organ is a developmental chimera built by recruiting three ancestral tissue programs. The appendage-selector gene Distal-less (Dll) establishes the glands primary proximal-distal structural axis. Downstream, the transcription factor sage maintains secretory epithelial identity by actively repressing a default neural program. Concurrently, the myogenic regulator sum-1 sustains epithelial lipid metabolism through paracrine Wnt signaling. These findings establish a mosaic model of organogenesis, demonstrating that radical evolutionary innovation can arise by forging morphogenetic and metabolic partnerships that harness adjacent tissues to fuel newly emerged structures.

Explore related subjects

evolutionary biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Zancolli, G., Hassan, A., McGregor, A. P., Moran, Y., Robinson-Rechavi, M.. 2026-07-16. A developmental chimera: co-option of appendage, secretory and myogenic programs underlies spider venom gland evolution. https://doi.org/10.64898/2026.07.10.737832

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

RELAX does not reproduce its own estimates at default settings, and its output does not show it

Selection-intensity estimates from RELAX are reported as a point value of K with a likelihood-ratio P. We report that, at default settings and on data of ordinary size, the program does not reproduce its own fits. Of 27 enzyme entries refitted under two optimiser configurations, none reproduced its log-likelihood to within 0.01 units; the median change was 103 units, the largest over 3,400, and four verdicts reversed. Eighty null orthologues reproduced none. A byte-identical command returned a distinct likelihood on every repetition, single-threaded, across three releases, and on alignments simulated under the fitted model, where 3.3 per cent of replicates reproduced. The documented random-number seed never reaches the generator when assigned on the command line, yet reads back as the value supplied. PAML localises the cause: its two-ratio model, without site classes, reproduced its log-likelihood for all 288 genes; its site-class models agreed for 27 to 67 per cent. The instability follows the mixture over sites, not the program. The output does not show it: 46 of 410 fits ended with a negative likelihood-ratio statistic, impossible under convergence, and 123 of 410 report a K re-estimated under a domain restriction rather than the unconstrained maximum. Of 234 published studies using RELAX, none reported a seed. Seeding while holding the thread count at one reproduced sixty of sixty runs on twenty genes under two releases; the seed alone reproduced none of five, and no documentation states the second condition. We recommend that fits be repeated and their dispersion published.

evolutionary biology↗
bioRxiv2026

Sequential accumulation of adaptive alleles forms an inversion supergene in deer mice

Supergenes are clusters of co-inherited loci that affect multiple or complex phenotypes. Despite the growing number of chromosomal inversions identified as supergenes in natural populations, their molecular basis and evolutionary history often remain obscure. Here, we identified two candidate genes, Slc45a2 and Npr3, within a 41-Mb inversion supergene in the deer mouse (Peromyscus maniculatus) that respectively drive darker coats and longer tails - two traits associated with forest adaptation. Mice homozygous for the inversion (inv/inv) exhibit elevated Slc45a2 expression in melanocytes relative to the congenic standard genotype (std/std), disrupting pheomelanin production. In parallel, downregulation of Npr3 in inv/inv mouse growth plates prolongs postnatal growth of caudal vertebrae, resulting in tail elongation. Population-level analyses further implicate that this supergene arose through the subsequent accumulation of the Npr3 allele within the inversion, rather than by capturing all beneficial mutations at its origin.

evolutionary biology↗
bioRxiv2026

Toxin structure shapes palatability in a chemically defended butterfly

The toxicity of chemical defences is well studied, but the potential contribution of compound structure to predator deterrence remains largely unexplored. Whether predation acts more strongly on toxicity or unpalatability remains largely untested, partly because few systems allow toxin structure to vary independently of quantity. Heliconius sara larvae provide such a system: those reared on Passiflora auriculata sequester cyclopentenyl cyanogenic glucosides (CGs), while those reared on P. biflora biosynthesise comparable quantities of aliphatic CGs. Using two invertebrate predators, Camponotus floridanus ants and Hierodula membranacea mantids, we tested whether this structural difference affects palatability independent of toxicity. Mantids rejected larvae with cyclopentenyl CGs more often than larvae with aliphatic CGs, despite no detectable difference in total CG content. This pattern was mirrored in extract-based assays with ants, independently of cyanide release: extracts with cyclopentenyl CGs remained deterrent, while extracts with aliphatic CGs did not differ in deterrence from water. Live larvae, by contrast, elicited similar responses from ants regardless of CG structure. These results show that variation in toxin structure can strongly affect palatability, with some compounds conferring greater protection than others. This demonstrates the importance of chemical structural diversity in the evolution of chemical defences.

evolutionary biology↗