tmc2a / tmc2b: identity, conserved synteny and public expression records
Scripts (run from the repo root; both query live APIs, nothing is hardcoded):
uv run python genes/DANRE/tmc2a/tmc2a-bioinformatics/pair_analysis.py tmc2a tmc2b TMC2 → output.txt
(Ensembl REST: locations, Compara orthologues/paralogy node, canonical proteins, 15 protein-coding neighbours
on each side of each copy with their gar and human orthologue positions, medaka co-orthologue locations).uv run python genes/DANRE/tmc2a/tmc2a-bioinformatics/expression_compare.py tmc2a tmc2b →
expression_output.txt (ZFIN wild-type expression download and Bgee REST calls).
Run 2026-09-28. Results below are copied from those output files.
Locations and Compara
- tmc2a chr5:55.22 Mb (+); tmc2b chr5:25.62 Mb (−); same chromosome, 29.6 Mb apart. tmc1 is at chr5:25.65 Mb,
next to tmc2b.
- Ensembl Compara paralogy node joining them: Osteoglossocephalai (identity 67-69%).
- One gar orthologue for both (ENSLOCG00000009603, LG2:33.97 Mb). One medaka one-to-one orthologue for each, on
different medaka chromosomes (tmc2a → chr12, tmc2b → chr9). Zebrafish-medaka identity (Compara, target %id):
tmc2a 76.9%, tmc2b 67.6%.
Protein identity (canonical Ensembl translations, global alignment, BLOSUM62)
| Pair |
Identity |
Similarity |
| tmc2a vs tmc2b |
68.4% |
78.7% |
| tmc2a vs gar TMC2 |
71.8% |
79.6% |
| tmc2b vs gar TMC2 |
67.2% |
76.9% |
| tmc2a vs human TMC2 |
56.6% |
71.2% |
| tmc2b vs human TMC2 |
56.0% |
69.8% |
| human TMC2 vs gar TMC2 |
58.6% |
72.1% |
tmc2b is further than tmc2a from both the gar and the medaka sequences: tmc2b has accumulated more change since the
duplication. The functional meaning, if any, is unknown.
Conserved synteny
- The gar TMC2 anchor (LG2:33.97 Mb) sits next to the gar orthologue of tmc1 (LG2:33.9 Mb), in a block whose human
orthologues are on 9q21 (70-77 Mb: TRPM3, KLF9, GDA, TMC1, ANXA1, RORB, TRPM6). Human TMC2 itself is on 20p13; so the
fish and human arrangements differ (which one is ancestral is not tested here). None of the 60 neighbours
maps within 5 Mb of human TMC2.
- tmc2b keeps that ancestral block: 14 of 30 neighbours have gar orthologues within 5 Mb of the gar anchor
(carnmt1 through klf9, including tmc1).
- tmc2a: only 1 of 30 (prune2, gar LG2:34.7 Mb). But 12 further tmc2a neighbours map to gar LG2 at other positions
(5.2-5.3 Mb and 40.5-46.3 Mb), and the tmc2a neighbourhood also contains human 9q21 genes (PRUNE2, GNA14, GNAQ at
76.6-77.7 Mb; HNRNPK, NTRK2 at 84 Mb).
- Both neighbourhoods also contain a second, shared block: gar LG21 / human 9q34 (fbxw5, tmem203, tprn, anapc2
near tmc2a; pnpla7b, mrpl41, dph7, paxx, abca2 near tmc2b; human 9:136.9-137.6 Mb).
Reading: the two zebrafish segments are each built from the same two ancestral blocks (gar LG2/human 9q21 and gar
LG21/human 9q34), which is the pattern expected for duplicated segments of one ancestral region. The tmc2a segment
has been rearranged relative to gar, so its micro-synteny around the gene itself is weak. The medaka copies are on
different chromosomes, as TGD ohnologs usually are; the zebrafish copies are on the same chromosome, which could
reflect a later rearrangement in the zebrafish lineage. This analysis does not by itself distinguish the TGD from a
large segmental duplication in the teleost stem; together with the PANTHER and Compara node placement it is
consistent with the TGD.
Public expression records
- ZFIN (curated; ZDB-PUB-140813-4 and ZDB-PUB-260425-13): both copies in inner ear, otic vesicle and neuromast;
tmc2a-only terms are crista and macula hair cells; tmc2b-only term is neuromast hair cell. This mirrors the
published papers rather than adding independent data.
- Bgee: no calls for tmc2a; tmc2b neuromast hair cell (in situ) and low bulk RNA-seq calls in muscle and tail. Not
hair-cell resolved; not interpreted.