title: Diversification and molecular evolution of ATOH8, a gene encoding a bHLH transcription factor.
abstract: ATOH8 is a bHLH domain transcription factor implicated in the development of the nervous system, kidney, pancreas, retina and muscle. In the present study, we collected sequence of ATOH8 orthologues from 18 vertebrate species and 24 invertebrate species. The reconstruction of ATOH8 phylogeny and sequence analysis showed that this gene underwent notable divergences during evolution. For those vertebrate species investigated, we analyzed the gene structure and regulatory elements of ATOH8. We found that the bHLH domain of vertebrate ATOH8 was highly conserved. Mammals retained some specific amino acids in contrast to the non-mammalian orthologues. Mammals also developed another potential isoform, verified by a human expressed sequence tag (EST). Comparative genomic analyses of the regulatory elements revealed a replacement of the ancestral TATA box by CpG-islands in the eutherian mammals and an evolutionary tendency for TATA box reduction in vertebrates in general. We furthermore identified the region of the effective promoter of human ATOH8 which could drive the expression of EGFP reporter in the chicken embryo. In the opossum, both the coding region and regulatory elements of ATOH8 have some special features, such as the unique extended C-terminus encoded by the third exon and absence of both CpG islands and TATA elements in the regulatory region. Our gene mapping data showed that in human, ATOH8 was hosted in one chromosome which is a fusion product of two orthologous chromosomes in non-human primates. This unique chromosomal environment of human ATOH8 probably subjects its expression to the regulation at chromosomal level. We deduce that the great interspecific differences found in both ATOH8 gene sequence and its regulatory elements might be significant for the fine regulation of its spatiotemporal expression and roles of ATOH8, thus orchestrating its function in different tissues and organisms.
authors.affiliation: Department of Anatomy and Molecular Embryology, Ruhr-University of Bochum, Bochum, Germany.
authors.forename: Jingchen
authors.initials: J
authors.lastname: Chen
authors.forename: Fangping
authors.initials: F
authors.lastname: Dai
authors.forename: Ajeesh
authors.initials: A
authors.lastname: Balakrishnan-Renuka
authors.forename: Florian
authors.initials: F
authors.lastname: Leese
authors.forename: Werner
authors.initials: W
authors.lastname: Schempp
authors.forename: Felix
authors.initials: F
authors.lastname: Schaller
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hoffmann
authors.forename: Gabriela
authors.initials: G
authors.lastname: Morosan-Puopolo
authors.forename: Faisal
authors.initials: F
authors.lastname: Yusuf
authors.forename: Izak Johannes
authors.initials: IJ
authors.lastname: Bisschoff
authors.forename: Verena
authors.initials: V
authors.lastname: Chankiewitz
authors.forename: Jinglun
authors.initials: J
authors.lastname: Xue
authors.forename: Jingzhong
authors.initials: J
authors.lastname: Chen
authors.forename: Kang
authors.initials: K
authors.lastname: Ying
authors.forename: Beate
authors.initials: B
authors.lastname: Brand-Saberi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D001499:Bayes Theorem; D002415:Cats; D002417:Cattle; D002642:Chick Embryo; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D014644:Genetic Variation; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007448:Invertebrates / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D011323:Primates; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014714:Vertebrates / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins