bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.10.13.682077

A Trade-off Between Developmental Speed and Replication Fidelity Governs the Spontaneous Mutation Rate

Bulut, B.·Pfenninger, M.
View original source ↗Export metadata ↓

Abstract

The spontaneous mutation rate () is shaped by two potentially opposing forces: the passage of chronological time, which is inevitably associated with mutation accumulation, and the speed of development, which may compromise replication fidelity. Disentangling these forces has been a major challenge, particularly in ectotherms. Testing the competing predictions of the classic time-dependent Generation Length Hypothesis and the replication-dependent speed-fidelity trade-off model, we experimentally assessed individuals with short (mean 15 days) and long (mean 37.7 days) generation time (GT) in the midge Chironomus riparius under constant temperature and estimated the de novo mutation rates by whole genome sequencing. We found that long-GT lines accumulated 1.3-fold more mutations per generation (/gen), consistent with time-dependent mutagenic processes. Conversely, short-GT lines exhibited a nearly two-fold higher mutation rate per day (/day) and a trend towards a transition-biased mutational spectrum (Ts/Tv ratio = 1.28 vs. 0.95), a pattern consistent with a speed-fidelity trade-off in DNA replication. These results suggest that two distinct processes shaped the overall mutation rate. Integrating our data with previous studies and life-history data, we show that the daily mutation rate followed a non-linear relationship with respect to generation time, and that the species generation time mode coincides with its minimum. This suggests that the generation time is, amongst other factors, selected to optimise the mutational load by balancing between replication accuracy and developmental speed. Teaser TextThe spontaneous mutation rate () is governed by a fundamental trade-off between the passage of time and the speed of development. We used the midge Chironomus riparius to experimentally disentangle these forces. We show that rapid development comes with a cost: compromised DNA replication fidelity and a high daily . Conversely, prolonged development accumulates mutations over time. Crucially, the species optimal generation time balances these opposing forces, falling precisely at the developmental speed that minimizes the overall mutational load, suggesting that selection for replication accuracy helps shape life-history evolution.

Explore related subjects

evolutionary biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Bulut, B., Pfenninger, M.. 2025-10-14. A Trade-off Between Developmental Speed and Replication Fidelity Governs the Spontaneous Mutation Rate. https://doi.org/10.1101/2025.10.13.682077

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↗