CG8915 helicase-motif comparison

CG8915/Q9VX63 retains a canonical ATP-binding P-loop and DEAH catalytic motif. It differs from the inactive helicase-like protein Bgcn/Q9W1I2 at both diagnostic regions. This supports a catalytically competent RNA-helicase inference for CG8915, without implying methyladenosine recognition or a meiotic pathway.

Using human YTHDC2/Q9H6S0 as the reference, both MAFFT strategies give:

Region	Human YTHDC2	CG8915	Bgcn control
Motif I	216–224 GETGSGKTT	232–240 GATGSGKST	171–179 AALCWDKSV
Motif II	316–319 DEVH	333–336 DEAH	269–272 NDVH

The whole-protein alignment identities over paired nongap positions are approximately 32.6–32.8% for CG8915 versus human YTHDC2 and 27.0–27.7% for Bgcn versus human YTHDC2. These alignments verify motif conservation; they are not a phylogeny and do not independently settle orthology or all accessory-domain relationships.

Biological grounding and limitations

Current FlyBase FBgn0030833 assigns YTHDC2 as the best bidirectional DIOPT human match (9/14 methods), and the target has an R3H domain, two helicase-core domains, HA2 and an OB fold. The target record does not contain a YTH-domain assignment. PMID:29033321(https://pubmed.ncbi.nlm.nih.gov/29033321/) directly demonstrates RNA-stimulated ATPase and 3′–5′ RNA-helicase activity for mammalian YTHDC2; the manually transferred FlyBase ISS assertion cites human Q9H6S0. This is conserved-function inference for CG8915, not a target enzymology experiment.

PMID:29360036(https://pmc.ncbi.nlm.nih.gov/articles/PMC5832417/), DOI:10.7554/eLife.30919, discusses divergence of Bgcn and states that Drosophila lacks a more YTHDC2-like version. Its main text does not name CG8915. That taxonomic conclusion cannot be used to equate CG8915 with Bgcn or to import Bgcn's altered motifs: the exact present sequences directly differ at those positions. Reconciling the historical family sampling with current CG8915 orthology would require a broader phylogeny; no such resolution is claimed here.

RNA binding is supported independently of the fine orthology question by the conserved RNA-helicase architecture and R3H domain. The broad ProtNLM nucleic-acid-binding claim remains supported even if future experiments revise the exact ATPase mechanism. No methyladenosine-binding, germline differentiation, nuclear localization or specific transcript is inferred from mammalian YTHDC2 studies.

Reproduction and controls

Run just in this directory with uv and MAFFT 7.526. Python dependencies are locked (Biopython 1.85). prepare.py extracts exact benchmark Q9VX63 JSON plus downloaded human YTHDC2 and fly Bgcn Swiss-Prot records. G-INS-i and L-INS-i alignments use --maxiterate 1000. analyze.py receives reference coordinates explicitly and records site mappings, alignment hashes and paired identities in JSON.

[x] Scripts accept all paths, identifiers and positions as arguments; conclusions are in this report only.
[x] Different-gene positive (YTHDC2) and divergent (Bgcn) controls were analyzed with the same scripts.
[x] Both alignments completed and independently agree on each displayed residue mapping.
[x] Input FASTA, source records, output alignments, logs and numeric summaries are retained.
[x] Sequence evidence is distinguished from unmeasured target activity and unresolved detailed phylogeny.

Sources: ../CG8915-uniprot-source.json from the frozen cohort; Q9H6S0 and Q9W1I2, saved as adjacent CG8915-reference-*-uniprot.txt files. Human reference positions were taken from the fetched sequence/ATP-binding feature and its DEVH motif.