sams-1
C. elegans
putative S-adenosylmethionine synthase 1
What the model saw
Gene: sams-1 Organism: Caenorhabditis elegans Known functions: putative S-adenosylmethionine synthase 1. ATP binding. methionine adenosyltransferase activity. protein binding.
View unredacted entry
putative S-adenosylmethionine synthase 1. ATP binding. methionine adenosyltransferase activity. protein binding.
Solver output
sams-1 encodes S-adenosylmethionine (SAM) synthase, which catalyzes the conversion of methionine and ATP into SAM, the universal methyl donor for virtually all cellular methylation reactions. In C. elegans, SAM is required for histone methylation (notably H3K4me3 via the COMPASS complex) and DNA methylation-equivalent marks, as well as phosphatidylcholine synthesis. Elevated SAM production by sams-1 fuels methionine cycle flux and supports active histone methylation states that promote growth and reproduction at the expense of longevity. Consistent with this, RNAi knockdown of sams-1 in C. elegans extends lifespan, partly by reducing H3K4me3 levels and altering lipid metabolism, mimicking methionine restriction—a well-established pro-longevity intervention. Thus, the normal (high) activity of sams-1 opposes longevity by sustaining methylation-driven anabolic and epigenetic programs that are detrimental to lifespan extension.
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 predicted anti_longevity for sams-1 in C. elegans. The mechanistic reasoning is excellent and well-supported: sams-1 encodes SAM synthase, and its knockdown extends lifespan by reducing H3K4me3 levels and altering lipid/methionine metabolism. The model correctly identifies the connection to methionine restriction as a pro-longevity intervention. The epigenetic_alterations mechanism class is appropriate given the H3K4me3 connection, though lipid metabolism also plays a role. The confidence of 0.75 is reasonable. Overall, this is a high-quality, accurate prediction with solid mechanistic reasoning.
Raw API responses
solver
{
"reasoning": "sams-1 encodes S-adenosylmethionine (SAM) synthase, which catalyzes the conversion of methionine and ATP into SAM, the universal methyl donor for virtually all cellular methylation reactions. In C. elegans, SAM is required for histone methylation (notably H3K4me3 via the COMPASS complex) and DNA methylation-equivalent marks, as well as phosphatidylcholine synthesis. Elevated SAM production by sams-1 fuels methionine cycle flux and supports active histone methylation states that promote growth and reproduction at the expense of longevity. Consistent with this, RNAi knockdown of sams-1 in C. elegans extends lifespan, partly by reducing H3K4me3 levels and altering lipid metabolism, mimicking methionine restriction—a well-established pro-longevity intervention. Thus, the normal (high) activity of sams-1 opposes longevity by sustaining methylation-driven anabolic and epigenetic programs that are detrimental to lifespan extension.",
"confidence": 0.75,
"key_pathways": [
"methionine cycle / SAM biosynthesis",
"histone H3K4 methylation (epigenetic regulation)",
"methionine restriction longevity pathway"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for sams-1 in C. elegans. The mechanistic reasoning is excellent and well-supported: sams-1 encodes SAM synthase, and its knockdown extends lifespan by reducing H3K4me3 levels and altering lipid/methionine metabolism. The model correctly identifies the connection to methionine restriction as a pro-longevity intervention. The epigenetic_alterations mechanism class is appropriate given the H3K4me3 connection, though lipid metabolism also plays a role. The confidence of 0.75 is reasonable. Overall, this is a high-quality, accurate prediction with solid mechanistic reasoning.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}