Evolutionary analysis of FAM83H in vertebrates
by Wushuang Huang, Mei Yang, Changning Wang, Yaling Song
Amelogenesis imperfecta is a group of disorders causing abnormalities in enamel formation in various phenotypes. Many mutations in the FAM83H gene have been identified to result in autosomal dominant hypocalcified amelogenesis imperfecta in different populations. However, the structure and function of FAM83H and its pathological mechanism have yet to be further explored. Evolutionary analysis is an alternative for revealing residues or motifs that are important for protein function. In the present study, we chose 50 vertebrate species in public databases representative of approximately 230 million years of evolution, including 1 amphibian, 2 fishes, 7 sauropsidas and 40 mammals, and we performed evolutionary analysis on the FAM83H protein. By sequence alignment, conserved residues and motifs were indicated, and the loss of important residues and motifs of five special species (Malayan pangolin, platypus, minke whale, nine-banded armadillo and aardvark) was discovered. A phylogenetic time tree showed the FAM83H divergent process. Positive selection sites in the C-terminus suggested that the C-terminus of FAM83H played certain adaptive roles during evolution. The results confirmed some important motifs reported in previous findings and identified some new highly conserved residues and motifs that need further investigation. The results suggest that the C-terminus of FAM83H contain key conserved regions critical to enamel formation and calcification.Publisher URL: http://journals.plos.org/plosone/article
DOI: 10.1371/journal.pone.0180360
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