Conservation of PCDHX in mammals; expression of human X/Y genes predominantly in brain

Protocadherins are members of the cadherin superfamily involved in cell-cel l interactions critical in the development of the central nervous system. T his paper describes the isolation, sequence, and expression analysis of two novel protocadherin genes from the hominid specific Yp11.2/Xq21.3 block of homology between the sex chromosomes. The X-(PCDHX) and Y-linked (PCDHY) g enes share 98.1% nucleotide and 98.3% amino acid identity and have an ident ical gene structure of six exons. The open reading frames of PCDHX and PCDH Y encode proteins of 1025 and 1037 amino acids respectively and specify sev en extracellular cadherin domains. Small differences in amino acid sequence affect regions that potentially have a large impact on function: thus, the X and Y genes may be differentiated in this respect. Sequence analysis of cDNA clones shows that both the X and Y loci are transcribed. RT-PCR expres sion analysis of mRNA from a variety of tissues and cell lines has demonstr ated that both transcripts are expressed predominantly in the brain, with d ifferential regional expression. From studies in the NTERA pluripotential c ell line (which differentiates along neuronal and spermatogenic pathways in response to retinoic acid), it emerges that the X and Y-linked genes are r egulated differently. This indicates that PCDHX and PCDHY possess different promoter regions. These findings suggest a role for PCDHX and PCDHY in the brain, consistent with the involvement of protocadherins in segmental brai n morphogenesis and function. The implications of Y-linked genes expressed predominantly in tissues and organs other than the testis are considered wi thin the context of the concept of sexual selection.