Independent expansion, selection, and hypervariability of the TBC1D3 gene family in humans

Human-specific C-terminal modification of TBC1D3. (A) The intron/exon structure of expressed TBC1D3 isoforms with protein-encoding ORFs. Each row constitutes a paralog-specific isoform observed based on Iso-Seq (Methods). All isoforms were mapped to human USP6 for a common reference. Exons are colored by species, with arches representing introns. (B) Amino acid sequence alignment of the C terminus of expressed primate TBC1D3 paralog sequences predicted from Iso-Seq full-length cDNA. All, and only, human-expressed copies contain a 43 bp deletion within the ORF of the terminal exon, resulting in a frameshift, creating an extension of 41 novel amino acids to the C terminus.