Figure 1: Diagrammatic illustration on the evolution of the SET/NAP/TSPY gene family. An ancestral gene gave rise to autosomal-located SET and NAP1 genes while one (TSPYL2) integrated onto the proto-X and proto-Y chromosomes. During the evolution of the sex chromosomes, the proto-Y chromosome had acquired a sex-determining gene and evolved into the modern Y chromosome, while the proto-X chromosome evolved into the X chromosome. The TSPYL2 gene on the Y chromosome had specialized to serve male-specific functions, such as spermatogenesis, amplified itself tandemly and became the ampliconic TSPY gene. The TSPYL2 gene on the X chromosome maintained likely the structure and functions of the ancestral gene and became the TSPX gene. Additional retrotransposition events, likely from TSPY transcripts, generated other intronless TSPY-like genes on the autosomes. The respective chromosomal locations are labeled on the left of each member of the gene family. NAP1: nucleosome assembly protein 1; SET: SET nuclear proto-oncogene; TSPX: TSPY homologue on the X chromosome; TSPY: testis-specific protein Y-encoded.