Abstract
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.
Highlights
The OFD1 gene has been implicated in several developmental syndromes, including a male-lethal Xlinked dominant condition, Oral-Facial-Digital type 1 (OFD1) syndrome [1], X-linked recessive Simpson-Golabi-Behmel syndrome type 2 (SGBS2) [2] and Joubert syndrome and related disorders (JSRDs) [3]
Our findings indicated that the mammalian OFD1X and OFD1Y were derived from the pair of ancestral autosomes during sex chromosome evolution
The bovine (Bos Taurus) Y chromosome (BTAY) contains a single copy OFD1Y in the X-degenerated region, which was proposed as a pseudogene in a previous report [28]
Summary
The OFD1 gene ( known as CXORF5) has been implicated in several developmental syndromes, including a male-lethal Xlinked dominant condition, Oral-Facial-Digital type 1 (OFD1) syndrome [1], X-linked recessive Simpson-Golabi-Behmel syndrome type 2 (SGBS2) [2] and Joubert syndrome and related disorders (JSRDs) [3]. The X-linked recessive SGBS2 and JSRD conditions are characterized by severe mental retardation and recurrent respiratory tract infections in both females and males [2,6]. Abnormal cilia formation and function are related to deregulation of signal transduction and several types of human disorders, which impact the development of body pattern and the physiology of organ systems [13,14,15]. The OFD1 gene family plays an important role in the ciliary formation and function during skeletal development [18]
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