ADE2
S. cerevisiae
phosphoribosylaminoimidazole carboxylase ADE2
What the model saw
Gene: ADE2 Organism: Saccharomyces cerevisiae Known functions: phosphoribosylaminoimidazole carboxylase ADE2. ATP binding. metal ion binding. phosphoribosylaminoimidazole carboxylase activity.
View unredacted entry
phosphoribosylaminoimidazole carboxylase ADE2. ATP binding. metal ion binding. phosphoribosylaminoimidazole carboxylase activity.
Solver output
ADE2 encodes phosphoribosylaminoimidazole carboxylase, a key enzyme in the de novo purine biosynthesis pathway in S. cerevisiae. Loss of ADE2 function leads to accumulation of the toxic intermediate AIR (5-aminoimidazole ribonucleotide), which is converted to a red pigment (P-ribosylamino-imidazole) and causes oxidative stress and mitochondrial dysfunction. Adequate purine nucleotide pools (ATP, GTP) are essential for DNA repair, RNA synthesis, and energy metabolism — all critical for maintaining cellular homeostasis and longevity. Furthermore, purine biosynthesis intersects with one-carbon metabolism and folate pathways, which influence epigenetic methylation and redox balance. ADE2 mutants are well-established as short-lived in yeast due to genotoxic stress from purine intermediate accumulation and impaired nucleotide availability, making the wild-type gene pro-longevity.
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 internally contradictory and ultimately wrong. The model correctly identifies that ADE2 mutants are short-lived (due to toxic intermediate accumulation and oxidative stress), which would make the wild-type gene pro-longevity — but the GenAge database classifies ADE2 as anti_longevity. This means that overexpression or presence of ADE2 actually reduces lifespan, or that deletion of ADE2 extends lifespan in some context. The model's mechanistic reasoning about purine biosynthesis and oxidative stress is partially accurate (ade2 mutants do accumulate red pigment and suffer oxidative stress), but the model drew the wrong conclusion about the longevity classification. The model was fairly confident (0.72) in its wrong answer. The ground truth classification of ADE2 as anti_longevity suggests that ADE2 activity (or the purine biosynthesis pathway it supports) promotes aging rather than longevity, which is counterintuitive and the model failed to anticipate this.
Raw API responses
solver
{
"reasoning": "ADE2 encodes phosphoribosylaminoimidazole carboxylase, a key enzyme in the de novo purine biosynthesis pathway in S. cerevisiae. Loss of ADE2 function leads to accumulation of the toxic intermediate AIR (5-aminoimidazole ribonucleotide), which is converted to a red pigment (P-ribosylamino-imidazole) and causes oxidative stress and mitochondrial dysfunction. Adequate purine nucleotide pools (ATP, GTP) are essential for DNA repair, RNA synthesis, and energy metabolism — all critical for maintaining cellular homeostasis and longevity. Furthermore, purine biosynthesis intersects with one-carbon metabolism and folate pathways, which influence epigenetic methylation and redox balance. ADE2 mutants are well-established as short-lived in yeast due to genotoxic stress from purine intermediate accumulation and impaired nucleotide availability, making the wild-type gene pro-longevity.",
"confidence": 0.72,
"key_pathways": [
"de novo purine biosynthesis",
"nucleotide pool maintenance",
"oxidative stress resistance"
],
"mechanism_class": "other",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted \"pro_longevity\" but the ground truth is \"anti_longevity.\" The model's reasoning is internally contradictory and ultimately wrong. The model correctly identifies that ADE2 mutants are short-lived (due to toxic intermediate accumulation and oxidative stress), which would make the wild-type gene pro-longevity — but the GenAge database classifies ADE2 as anti_longevity. This means that overexpression or presence of ADE2 actually reduces lifespan, or that deletion of ADE2 extends lifespan in some context. The model's mechanistic reasoning about purine biosynthesis and oxidative stress is partially accurate (ade2 mutants do accumulate red pigment and suffer oxidative stress), but the model drew the wrong conclusion about the longevity classification. The model was fairly confident (0.72) in its wrong answer. The ground truth classification of ADE2 as anti_longevity suggests that ADE2 activity (or the purine biosynthesis pathway it supports) promotes aging rather than longevity, which is counterintuitive and the model failed to anticipate this.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": true
}