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ergo-1

C. elegans

Piwi domain-containing protein;Piwi-like protein ergo-1

What the model saw

Gene: ergo-1
Organism: Caenorhabditis elegans
Known functions: Piwi domain-containing protein;Piwi-like protein ergo-1. DEAD/H-box RNA helicase binding. RNA binding. RNA endonuclease activity. miRNA binding. nucleic acid binding. siRNA binding. single-stranded RNA binding.
View unredacted entry
Piwi domain-containing protein;Piwi-like protein ergo-1. DEAD/H-box RNA helicase binding. RNA binding. RNA endonuclease activity. miRNA binding. nucleic acid binding. siRNA binding. single-stranded RNA binding.

Solver output

Predicted influence
Pro-longevity
Confidence
62%
Mechanism
Genomic instability
Reasoning

ergo-1 encodes a Piwi-domain-containing Argonaute-family protein in C. elegans that binds siRNA (specifically 26G-RNAs) and engages DEAD/H-box RNA helicases to mediate endogenous RNA interference pathways. Piwi-clade proteins are central to the piRNA/endo-siRNA surveillance system that silences transposable elements and repetitive genomic sequences; loss of this silencing leads to transposon mobilization and genomic instability, a recognized hallmark of aging. In C. elegans, the endo-siRNA pathway coordinated by ergo-1 also feeds into germline epigenetic inheritance and maintenance of genome integrity across generations. Additionally, small-RNA-mediated gene silencing pathways in C. elegans (including those involving Argonaute proteins) intersect with longevity regulation through the germline signaling axis. By suppressing transposon activity and maintaining RNA homeostasis, ergo-1's normal function is expected to support genomic stability and thus promote longevity.

Key pathways
endogenous siRNA (endo-siRNA/26G-RNA) pathwaytransposable element silencing via Piwi-clade Argonautegermline genome integrity maintenance
Longevity influence
Anti-longevity
Lifespan effect
Increase

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

Answer
Incorrect
Mechanism
Incorrect
Reasoning quality
2/5
Failure mode
Confident wrong
Notes

The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is plausible on the surface - it correctly identifies ergo-1 as a Piwi-domain Argonaute involved in endo-siRNA pathways and transposon silencing - but then incorrectly concludes that this function would promote longevity. The actual finding in C. elegans is that ergo-1 is anti-longevity, meaning its loss or reduction extends lifespan. The model failed to consider that ergo-1 might negatively regulate longevity pathways, perhaps by silencing genes that promote longevity or by competing with other small RNA pathways that extend lifespan. The model's confidence of 0.62 is moderate but still wrong. The mechanistic reasoning about genomic instability and transposon silencing promoting longevity is speculative and ultimately incorrect in this context.

Raw API responses

solver

{
  "reasoning": "ergo-1 encodes a Piwi-domain-containing Argonaute-family protein in C. elegans that binds siRNA (specifically 26G-RNAs) and engages DEAD/H-box RNA helicases to mediate endogenous RNA interference pathways. Piwi-clade proteins are central to the piRNA/endo-siRNA surveillance system that silences transposable elements and repetitive genomic sequences; loss of this silencing leads to transposon mobilization and genomic instability, a recognized hallmark of aging. In C. elegans, the endo-siRNA pathway coordinated by ergo-1 also feeds into germline epigenetic inheritance and maintenance of genome integrity across generations. Additionally, small-RNA-mediated gene silencing pathways in C. elegans (including those involving Argonaute proteins) intersect with longevity regulation through the germline signaling axis. By suppressing transposon activity and maintaining RNA homeostasis, ergo-1's normal function is expected to support genomic stability and thus promote longevity.",
  "confidence": 0.62,
  "key_pathways": [
    "endogenous siRNA (endo-siRNA/26G-RNA) pathway",
    "transposable element silencing via Piwi-clade Argonaute",
    "germline genome integrity maintenance"
  ],
  "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 plausible on the surface - it correctly identifies ergo-1 as a Piwi-domain Argonaute involved in endo-siRNA pathways and transposon silencing - but then incorrectly concludes that this function would promote longevity. The actual finding in C. elegans is that ergo-1 is anti-longevity, meaning its loss or reduction extends lifespan. The model failed to consider that ergo-1 might negatively regulate longevity pathways, perhaps by silencing genes that promote longevity or by competing with other small RNA pathways that extend lifespan. The model's confidence of 0.62 is moderate but still wrong. The mechanistic reasoning about genomic instability and transposon silencing promoting longevity is speculative and ultimately incorrect in this context.",
  "failure_mode": "confident_wrong",
  "answer_correct": false,
  "mechanism_correct": false,
  "reasoning_quality": 2,
  "ground_truth_questionable": false
}
ergo-1 · Caenorhabditis elegans | Aging biology eval