rnr-2
C. elegans
Ribonucleoside-diphosphate reductase small chain
What the model saw
Gene: rnr-2 Organism: Caenorhabditis elegans Known functions: Ribonucleoside-diphosphate reductase small chain. oxidoreductase activity. ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor.
View unredacted entry
Ribonucleoside-diphosphate reductase small chain. oxidoreductase activity. ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor.
Solver output
rnr-2 encodes the small (R2) subunit of ribonucleoside-diphosphate reductase (RNR), the enzyme that catalyzes the rate-limiting step in de novo dNTP biosynthesis by reducing ribonucleoside diphosphates to deoxyribonucleoside diphosphates using thioredoxin as the electron donor. Adequate and balanced dNTP pools are essential for accurate DNA replication and repair; insufficient RNR activity leads to replication stress, stalled forks, and accumulation of DNA damage—hallmarks of genomic instability that accelerate aging. By maintaining sufficient dNTP supply, rnr-2 supports high-fidelity DNA synthesis and efficient DNA damage repair, thereby opposing genomic instability. Loss of RNR function in model organisms is associated with increased mutation rates and shortened lifespan, consistent with a pro-longevity role for the wild-type gene. The thioredoxin-dependent redox mechanism also links this enzyme to cellular redox homeostasis, further supporting genome maintenance.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is based on a general assumption that RNR activity supports genome maintenance and therefore longevity, but this is incorrect for rnr-2 in C. elegans. The actual finding is that rnr-2 is anti-longevity, meaning its loss or reduction extends lifespan. This is consistent with research showing that reducing dNTP pools or RNR activity can extend lifespan in C. elegans, possibly through mechanisms related to DNA replication rate, metabolic signaling, or other pathways. The model's mechanistic reasoning (that RNR supports genome integrity and therefore is pro-longevity) is plausible in general but wrong in this specific context. The model had moderate confidence (0.62) but was still clearly wrong on both the answer and the mechanism.
Raw API responses
solver
{
"reasoning": "rnr-2 encodes the small (R2) subunit of ribonucleoside-diphosphate reductase (RNR), the enzyme that catalyzes the rate-limiting step in de novo dNTP biosynthesis by reducing ribonucleoside diphosphates to deoxyribonucleoside diphosphates using thioredoxin as the electron donor. Adequate and balanced dNTP pools are essential for accurate DNA replication and repair; insufficient RNR activity leads to replication stress, stalled forks, and accumulation of DNA damage—hallmarks of genomic instability that accelerate aging. By maintaining sufficient dNTP supply, rnr-2 supports high-fidelity DNA synthesis and efficient DNA damage repair, thereby opposing genomic instability. Loss of RNR function in model organisms is associated with increased mutation rates and shortened lifespan, consistent with a pro-longevity role for the wild-type gene. The thioredoxin-dependent redox mechanism also links this enzyme to cellular redox homeostasis, further supporting genome maintenance.",
"confidence": 0.62,
"key_pathways": [
"dNTP biosynthesis / DNA replication fidelity",
"DNA damage repair",
"thioredoxin-mediated redox regulation"
],
"mechanism_class": "genomic_instability",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is based on a general assumption that RNR activity supports genome maintenance and therefore longevity, but this is incorrect for rnr-2 in C. elegans. The actual finding is that rnr-2 is anti-longevity, meaning its loss or reduction extends lifespan. This is consistent with research showing that reducing dNTP pools or RNR activity can extend lifespan in C. elegans, possibly through mechanisms related to DNA replication rate, metabolic signaling, or other pathways. The model's mechanistic reasoning (that RNR supports genome integrity and therefore is pro-longevity) is plausible in general but wrong in this specific context. The model had moderate confidence (0.62) but was still clearly wrong on both the answer and the mechanism.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}