Linkage of human spermatid-specific basic nuclear protein genes. Definition and evolution of the P1-->P2-->TP2 locus.

Protamines and transition proteins are highly basic sperm-specific nuclear proteins that serve to compact the DNA within the condensing spermatid nucleus. It has been proposed that the genes for protamine P1 and P2 and transition protein 2 may be clustered at a single loci. This may have marked implications for their evolution and coordinate developmental regulation. The cloning of a contiguous segment encompassing this region would directly address these issues. We have utilized a cloned segment of the human protamine P1 gene to isolate a human cosmid clone which contains the genes for protamines P1 and P2 and transition protein TP2. Sequence and hybridization analysis of this cosmid showed that the TP2 gene resided 3' of the P2 gene at a distance of approximately 7 kilobases (kb). This establishes the order of this gene cluster within a 13-kb region of 16p13.13-16p13.2 to be P1-->P2-->TP2. Similar to their spatial order, comparative computer-assisted sequence analysis predicts an identical relative rank order of emergence. Accordingly we propose that this gene cluster may have arisen from the P1 gene through a series of gene duplication events.