mars-1
C. elegans
Methionine--tRNA ligase, cytoplasmic;tRNA-binding domain-containing protein
What the model saw
Gene: mars-1 Organism: Caenorhabditis elegans Known functions: Methionine--tRNA ligase, cytoplasmic;tRNA-binding domain-containing protein. ATP binding. aminoacyl-tRNA ligase activity. methionine-tRNA ligase activity. nucleotide binding. tRNA binding.
View unredacted entry
Methionine--tRNA ligase, cytoplasmic;tRNA-binding domain-containing protein. ATP binding. aminoacyl-tRNA ligase activity. methionine-tRNA ligase activity. nucleotide binding. tRNA binding.
Solver output
mars-1 encodes the cytoplasmic methionine-tRNA ligase (MetRS), which charges tRNA-Met with methionine as the first step in translation initiation. Beyond its canonical aminoacylation role, MetRS/MARS enzymes are known to moonlight as sensors of methionine availability, directly linking amino acid sufficiency to mTORC1 activation via the GATOR/Ragulator complex. In C. elegans, methionine restriction extends lifespan, and reduced methionine-tRNA ligase activity would be expected to dampen mTORC1 signaling and translation rates, mimicking dietary restriction. Loss-of-function of mars-1 would thus phenocopy methionine restriction, reducing global protein synthesis and activating longevity pathways downstream of reduced TOR activity. The gene's normal (wild-type) function therefore promotes mTORC1 activity and opposes longevity, making it anti-longevity; however, as a housekeeping aminoacyl-tRNA synthetase essential for proteostasis, its complete loss would be detrimental, creating some ambiguity. The balance of evidence from methionine-sensing and TOR-nutrient signaling literature supports classifying the normal function as net anti-longevity through sustained nutrient/TOR signaling.
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." Interestingly, the model's own reasoning actually argues for anti_longevity (stating "the normal function therefore promotes mTORC1 activity and opposes longevity, making it anti-longevity"), yet the final prediction label is "pro_longevity." This is a direct internal contradiction — the reasoning reaches the correct conclusion but the final answer is wrong. The mechanistic reasoning about methionine restriction and TOR signaling is plausible but speculative and not well-grounded in C. elegans-specific literature for mars-1. The model appears to have confused itself in the final classification step, outputting "pro_longevity" despite its own reasoning supporting "anti_longevity."
Raw API responses
solver
{
"reasoning": "mars-1 encodes the cytoplasmic methionine-tRNA ligase (MetRS), which charges tRNA-Met with methionine as the first step in translation initiation. Beyond its canonical aminoacylation role, MetRS/MARS enzymes are known to moonlight as sensors of methionine availability, directly linking amino acid sufficiency to mTORC1 activation via the GATOR/Ragulator complex. In C. elegans, methionine restriction extends lifespan, and reduced methionine-tRNA ligase activity would be expected to dampen mTORC1 signaling and translation rates, mimicking dietary restriction. Loss-of-function of mars-1 would thus phenocopy methionine restriction, reducing global protein synthesis and activating longevity pathways downstream of reduced TOR activity. The gene's normal (wild-type) function therefore promotes mTORC1 activity and opposes longevity, making it anti-longevity; however, as a housekeeping aminoacyl-tRNA synthetase essential for proteostasis, its complete loss would be detrimental, creating some ambiguity. The balance of evidence from methionine-sensing and TOR-nutrient signaling literature supports classifying the normal function as net anti-longevity through sustained nutrient/TOR signaling.",
"confidence": 0.55,
"key_pathways": [
"mTORC1/TOR nutrient sensing via methionine availability",
"methionine restriction longevity pathway",
"aminoacyl-tRNA synthetase-mediated translation regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted \"pro_longevity\" but the ground truth is \"anti_longevity.\" Interestingly, the model's own reasoning actually argues for anti_longevity (stating \"the normal function therefore promotes mTORC1 activity and opposes longevity, making it anti-longevity\"), yet the final prediction label is \"pro_longevity.\" This is a direct internal contradiction — the reasoning reaches the correct conclusion but the final answer is wrong. The mechanistic reasoning about methionine restriction and TOR signaling is plausible but speculative and not well-grounded in C. elegans-specific literature for mars-1. The model appears to have confused itself in the final classification step, outputting \"pro_longevity\" despite its own reasoning supporting \"anti_longevity.\"",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}