Regional selection acting on the OFD1 gene family.
The OFD1 (oral-facial-digital, type 1) gene is implicated in several developmental disorders in humans. The X-linked OFD1 (OFD1X) is conserved in Eutheria. Knowledge about the Y-linked paralog (OFD1Y) is limited. In this study, we identified an OFD1Y on the bovine Y chromosome, which is expressed differentially from the bovine OFD1X. Phylogenetic analysis indicated that: a) the eutherian OFD1X and OFD1Y were derived from the pair of ancestral autosomes during sex chromosome evolution; b) the autosomal OFD1 pseudogenes, present in Catarrhini and Murinae, were derived from retropositions of OFD1X after the divergence of primates and rodents; and c) the presence of OFD1Y in the ampliconic region of the primate Y chromosome is an indication that the expansion of the ampliconic region may initiate from the X-degenerated sequence. In addition, we found that different regions of OFD1/OFD1X/OFD1Y are under differential selection pressures. The C-terminal half of OFD1 is under relaxed selection with an elevated Ka/Ks ratio and clustered positively selected sites, whereas the N-terminal half is under stronger constraints. This study provides some insights into why the OFD1X gene causes OFD1 (male-lethal X-linked dominant) and SGBS2 & JSRDs (X-linked recessive) syndromes in humans, and reveals the origin and evolution of the OFD1 family, which will facilitate further clinical investigation of the OFD1-related syndromes.
Department of Dairy and Animal Science, The Center for Reproductive Biology and Health, College of Agricultural Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America.
Ti-Cheng
TC
Chang
Jessica L
JL
Klabnik
Wan-Sheng
WS
Liu
D000818:Animals; D002417:Cattle; D019143:Evolution, Molecular; D005260:Female; D015894:Genome, Human / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D005810:Multigene Family / Q000235:genetics*; D010641:Phenotype; D010802:Phylogeny; D011506:Proteins / Q000235:genetics*; D011544:Pseudogenes / Q000235:genetics; D012641:Selection, Genetic; D014998:Y Chromosome / Q000235:genetics
D011506:Proteins