Little is known about protein sequences unique in humans. Here, we performed alignment-free sequence comparisons based on the availability (frequency bias) of short constituent amino acid (aa) sequences (SCSs) in proteins to search for human-specific proteins. Focusing on 5-aa SCSs (pentats), exhaustive comparisons of availability scores among the human proteome and other nine mammalian proteomes in the nonredundant (nr) database identified a candidate protein containing WRWSH, here called FAM75, as human-specific. Examination of various human genome sequences revealed that FAM75 had genomic DNA sequences for either WRWSH or WRWSR due to a single nucleotide polymorphism (SNP). FAM75 and its related protein FAM205A were found to be produced through alternative splicing. The FAM75 transcript was found only in humans, but the FAM205A transcript was also present in other mammals. In humans, both FAM75 and FAM205A were expressed specifically in testis at the mRNA level, and they were immunohistochemically located in cells in seminiferous ducts and in acrosomes in spermatids at the protein level, suggesting their possible function in sperm development and fertilization. This study highlights a practical application of SCS-based methods for protein searches and suggests possible contributions of SNP variants and alternative splicing of FAM75 to human evolution.
Part of the book: Computational Biology and Chemistry