Comparative and evolutionary analysis of the HES/HEY gene family reveal exon/intron loss and teleost specific duplication events.
BACKGROUND
HES/HEY genes encode a family of basic helix-loop-helix (bHLH) transcription factors with both bHLH and Orange domain. HES/HEY proteins are direct targets of the Notch signaling pathway and play an essential role in developmental decisions, such as the developments of nervous system, somitogenesis, blood vessel and heart. Despite their important functions, the origin and evolution of this HES/HEY gene family has yet to be elucidated.


RESULTS
In this study, we identified genes of the HES/HEY family in representative species and performed evolutionary analysis to elucidate their origin and evolutionary process. Our results showed that the HES/HEY genes only existed in metazoans and may originate from the common ancestor of metazoans. We identified HES/HEY genes in more than 10 species representing the main lineages. Combining the bHLH and Orange domain sequences, we constructed the phylogenetic trees by different methods (Bayesian, ML, NJ and ME) and classified the HES/HEY gene family into four groups. Our results indicated that this gene family had undergone three expansions, which were along with the origins of Eumetazoa, vertebrate, and teleost. Gene structure analysis revealed that the HES/HEY genes were involved in exon and/or intron loss in different species lineages. Genes of this family were duplicated in bony fishes and doubled than other vertebrates. Furthermore, we studied the teleost-specific duplications in zebrafish and investigated the expression pattern of duplicated genes in different tissues by RT-PCR. Finally, we proposed a model to show the evolution of this gene family with processes of expansion, exon/intron loss, and motif loss.


CONCLUSIONS
Our study revealed the evolution of HES/HEY gene family, the expression and function divergence of duplicated genes, which also provide clues for the research of Notch function in development. This study shows a model of gene family analysis with gene structure evolution and duplication.
Hubei Bioinformatics and Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Mi
M
Zhou
Jun
J
Yan
Zhaowu
Z
Ma
Yang
Y
Zhou
Nibras Najm
NN
Abbood
Jianfeng
J
Liu
Li
L
Su
Haibo
H
Jia
An-Yuan
AY
Guo
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000145:classification / Q000235:genetics*; D001499:Bayes Theorem; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics*; D017353:Gene Deletion; D020440:Gene Duplication / Q000235:genetics*; D005786:Gene Expression Regulation; D056426:Genetic Loci / Q000235:genetics; D016678:Genome / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D059372:Nucleotide Motifs / Q000235:genetics; D010802:Phylogeny; D016415:Sequence Alignment; D013045:Species Specificity; D015027:Zebrafish / Q000235:genetics*
D051792:Basic Helix-Loop-Helix Proteins