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: 720 rows, 480 ACCEPT (67%).
  • None of the 97 protein binding rows was accepted; wrong electronic terms were removed or redirected to the gene's actual mechanism.

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 MODIFY → G1 to G0 transition
ATG7 GO:0006501 C-terminal protein lipidation (6 rows) MODIFY → Atg8 conjugation to PE

Plus 97 protein binding (GO:0005515) rows across 15 genes: 59 over-annotated, 26 removed, 7 modified, 5 non-core.

Status and next steps

  • ✅ 20/20 gene reviews complete (genes/yeast/<GENE>/<GENE>-ai-review.yaml).
  • The phase tallies in the project page (842 rows, 510 ACCEPT) were recorded in Dec 2025 and differ from the current files; the counts here come from the YAMLs.
  • Open: 4 UNDECIDED rows (SIR3, HST2 ×2, RAS2); no module or pathway summary yet.

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