Template choice can create apparent protein-stability links to lifespan in tetrapods
In two tetrapod radiations, predicted protein stability showed no robust association with longevity once outgroup templates were used; the structural template itself can create apparent links. [1]
Automatic summary · not editorially reviewed
The key findings
The study examined 57 placental mammals (1,755 genes) and 40 reptiles and amphibians (1,910 genes) in two independent tetrapod radiations. [1]
With a platypus backbone, the primate offset fell from -1.96 to -0.62 SD and the lifespan association disappeared (P = 0.701). [1]
With outgroup templates, neither radiation showed a robust association between predicted stability and longevity, though moderate effects cannot be excluded. [1]
The source at a glance
- Study type / format
- Comparative computational study (abstract)
- Population / context
- 57 placental mammals and 40 reptiles and amphibians in two tetrapod radiations
- Summary based on
- Study abstract
- Publication status
- Preprint · peer-review status not confirmed
- Original publication
- October 16, 2026
Testing stability versus longevity in mammals and reptiles
The authors asked whether long-lived species carry proteins predicted to be more stable or, under nearly neutral theory, less stable. They studied two independent tetrapod radiations: 57 placental mammals (1,755 genes) and 40 reptiles and amphibians (1,910 genes). They reconstructed ancestral proteins and predicted the folding effect of every amino-acid difference between ancestor and species, then related the mean effect to lifespan by phylogenetic regression, following analysis plans fixed in advance.
Supporting source [1]
Human backbone showed weak link; platypus backbone removed it
With a human backbone, primates, which are long-lived for their size, appeared least destabilized, producing a weak apparent association with lifespan. In a pre-specified confirmatory test, a platypus backbone reduced the primate offset from -1.96 to -0.62 SD and the association disappeared (P = 0.701). In reptiles, a human backbone, although equidistant in time, favoured slowly evolving turtles and crocodilians and gave a nominal association that two fish backbones did not reproduce.
Supporting source [1]
No robust link; four proposed checks for template effects
The predictor captured site-level stability signal, yet with outgroup templates neither radiation showed a robust association between predicted stability and longevity, although moderate effects cannot be excluded. The authors conclude that the choice of structural template can create apparent cross-species associations. They propose four checks to detect them: ancestral references, outgroup templates, tests for clade and rate effects, and tests of dependence on a few clades.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. This is a comparative computational analysis of predicted protein stability, not a test of human lifespan or a causal claim. Moderate effects cannot be excluded.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Torres Alegre EO, Mora Jimenez DE. · europepmc.org · October 16, 2026