mev-1
C. elegans
Succinate dehydrogenase cytochrome b560 subunit, mitochondrial
What the model saw
Gene: mev-1 Organism: Caenorhabditis elegans Known functions: Succinate dehydrogenase cytochrome b560 subunit, mitochondrial. electron transfer activity. heme binding. succinate dehydrogenase (quinone) activity.
View unredacted entry
Succinate dehydrogenase cytochrome b560 subunit, mitochondrial. electron transfer activity. heme binding. succinate dehydrogenase (quinone) activity.
Solver output
mev-1 encodes the cytochrome b560 subunit (SDHC) of mitochondrial Complex II (succinate dehydrogenase), which couples succinate oxidation to ubiquinone reduction in the electron transport chain. Loss-of-function mutations in mev-1 are well-characterized in C. elegans as causing hypersensitivity to oxidative stress and a shortened lifespan due to excessive superoxide production at Complex II, resulting from impaired electron transfer to ubiquinone. The normal function of this subunit is essential for efficient electron flow; when disrupted, electrons leak and generate reactive oxygen species (ROS), accelerating mitochondrial dysfunction and aging. Because the wild-type gene's normal activity is required to prevent this ROS overproduction, its intact function is necessary for normal (not extended) lifespan — but its dysfunction is a canonical cause of shortened lifespan, classifying it as anti-longevity in the context of its mutant phenotype driving accelerated aging via mitochondrial electron transport chain impairment.
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 correctly identifies the mechanism: mev-1 encodes the SDHC subunit of Complex II, and loss-of-function mutations cause excessive ROS production and shortened lifespan. However, the model incorrectly classifies mev-1 as "anti_longevity" when the GenAge database classifies it as "pro_longevity." The model's reasoning about the mutant phenotype is accurate (mev-1 mutants are short-lived), but it misapplies the GenAge classification convention. In GenAge, a gene is "pro_longevity" when its normal function promotes longevity (i.e., loss-of-function shortens lifespan), which is exactly the case here. The model explicitly acknowledges this logic but then contradicts itself by labeling it "anti_longevity." The model was highly confident (0.92) in the wrong answer despite correctly understanding the biology. This is a classification convention error with correct mechanistic understanding.
Raw API responses
solver
{
"reasoning": "mev-1 encodes the cytochrome b560 subunit (SDHC) of mitochondrial Complex II (succinate dehydrogenase), which couples succinate oxidation to ubiquinone reduction in the electron transport chain. Loss-of-function mutations in mev-1 are well-characterized in C. elegans as causing hypersensitivity to oxidative stress and a shortened lifespan due to excessive superoxide production at Complex II, resulting from impaired electron transfer to ubiquinone. The normal function of this subunit is essential for efficient electron flow; when disrupted, electrons leak and generate reactive oxygen species (ROS), accelerating mitochondrial dysfunction and aging. Because the wild-type gene's normal activity is required to prevent this ROS overproduction, its intact function is necessary for normal (not extended) lifespan — but its dysfunction is a canonical cause of shortened lifespan, classifying it as anti-longevity in the context of its mutant phenotype driving accelerated aging via mitochondrial electron transport chain impairment.",
"confidence": 0.92,
"key_pathways": [
"mitochondrial electron transport chain (Complex II)",
"reactive oxygen species (ROS) generation",
"oxidative stress response"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly identifies the mechanism: mev-1 encodes the SDHC subunit of Complex II, and loss-of-function mutations cause excessive ROS production and shortened lifespan. However, the model incorrectly classifies mev-1 as \"anti_longevity\" when the GenAge database classifies it as \"pro_longevity.\" The model's reasoning about the mutant phenotype is accurate (mev-1 mutants are short-lived), but it misapplies the GenAge classification convention. In GenAge, a gene is \"pro_longevity\" when its normal function promotes longevity (i.e., loss-of-function shortens lifespan), which is exactly the case here. The model explicitly acknowledges this logic but then contradicts itself by labeling it \"anti_longevity.\" The model was highly confident (0.92) in the wrong answer despite correctly understanding the biology. This is a classification convention error with correct mechanistic understanding.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}