The T2T-CHM13 reference assembly uncovers essential WASH1 and GPRIN2 paralogues.

SUMMARY

The recently published T2T-CHM13 reference assembly completed the annotation of the final 8% of the human genome. It introduced 1956 genes, close to 100 of which are predicted to be coding because they have a protein coding parent gene. Here, we confirm the coding status and functional relevance of two of these genes, paralogues of and . We find that , one of four novel subtelomeric WASH1 genes uncovered in the new assembly, produces the WASH1 protein that forms part of the vital actin-regulatory WASH complex. Its coding status is supported by abundant proteomics, conservation, and cDNA evidence. It was previously assumed that gene produced the functional WASH1 protein, but new evidence shows that is a human-derived duplication and likely to be one of 12 WASH1 pseudogenes in the human gene set. We also find that the T2T-CHM13 assembly has added a functionally important copy of to the human gene set. We demonstrate that uniquely mapping peptides from proteomics databases support the novel rather than the GRCh38 assembly gene. These new additions to the set of human coding genes underlines the importance of the new T2T-CHM13 assembly.

AVAILABILITY AND IMPLEMENTATION

None.