Yeast replicative aging

Reviewing GO annotations for 20 genes that set how many times a yeast cell can divide

AI Gene Review · projects/YEAST_REPLICATIVE_AGING · 2025–2026

Bottom line

  • Replicative lifespan in budding yeast depends on sirtuins and NAD+, respiration and ROS defence, mRNA fate and translation, nutrient signalling and proteostasis.
  • We reviewed every GO annotation on 20 genes across those five areas: 732 existing rows plus 4 proposed NEW rows, 483 ACCEPT.
  • None of the 98 protein binding rows was accepted; wrong electronic terms were removed and valid conditional terms were moved out of the core set.

Why this set

  • Yeast aging is a phenotype. GO should describe what each gene product does, not that its deletion shortens or extends lifespan.
  • Five mechanisms, 20 genes: a test of whether per-gene review keeps catalytic, regulatory and structural roles apart.
    • SIR2 deacetylates; SIR3 and SIR4 are the structural partners.
    • HAP4 activates respiratory genes but is not a respiratory-chain component.
    • CAT2 is a carnitine acetyltransferase, despite its name.

The five mechanisms

Results per gene

What a review looks like

RIM15 review page: each GOA row gets an action, a written reason and quoted evidence. The IBA kinase-activity row is accepted on direct biochemical evidence.

Corrections that recur

Gene Term (evidence) Action
SPA2 GO:0005826 actomyosin contractile ring (IBA) REMOVE
DBP5 GO:0015031 protein transport (IEA) REMOVE
LSM1 GO:0006397 mRNA processing (IEA) REMOVE
HAP4 GO:0003677 DNA binding (IEA); GO:0098803 respiratory chain complex (IMP) REMOVE
RIM15 GO:1901992 positive regulation of mitotic cell cycle phase transition KEEP_AS_NON_CORE
ATG7 GO:0006501 C-terminal protein lipidation (6 rows) MODIFY → Atg8 conjugation to PE

Plus 98 protein binding (GO:0005515) rows across 15 genes: 86 removed, 7 modified, 5 over-annotated.

Status and next steps

  • ✅ 20/20 gene reviews complete (genes/yeast/<GENE>/<GENE>-ai-review.yaml).
  • The December 2025 notes retain older 842-row/510-ACCEPT tallies; the active page and this deck are recounted from the YAMLs.
  • Open: 5 UNDECIDED rows (SIR3, HST2 ×3, RAS2) and no module or pathway summary yet; tracked in #4027.

Read more: projects/YEAST_REPLICATIVE_AGING.md · genes/yeast/