Evolution, Functional Divergence and Conserved Exon-intron Structure of BHLH/PAS Gene Family

Overview

Journal Mol Genet Genomics

Specialty Genetics

Date 2013 Nov 9

PMID 24202550

Citations 12

Authors

Jun Yan

Zhaowu Ma

Xiaopeng Xu

An-Yuan Guo

Affiliations

Soon will be listed here.

Abstract

bHLH/PAS genes encode a family of basic helix-loop-helix (bHLH) transcription factors with bHLH, PAS and PAS_3 domain. bHLH/PAS genes are involved in many essential physiological and developmental processes, such as hypoxic response neural development, the circadian clock, and learning ability. Despite their important functions, the origin and evolution of this bHLH/PAS gene family has yet to be elucidated. In this study, we aim to explore the origin, evolution, gene structure conservation of this gene family and provide a model to analyze the evolution of other gene families. Our results show that genes of the bHLH/PAS family only exist in metazoans. They may have originated from the common ancestor of metazoans and expanded into vertebrates. We identified bHLH/PAS genes in more than ten species representing the main lineages and constructed the phylogenetic trees (Beyasian, ML and NJ) to classify them into three groups. The exon-intron structure analysis revealed that a relatively conserved "1001-0210" eight-exon structure exists in most groups and lineages. In addition, we found the exon fusion pattern in several groups in this conserved eight-exon structure. Further analysis indicated that bHLH/PAS protein paralogs evolved from several gene duplication events followed by functional divergence and purifying selection. We presented a phylogenetic model to describe the evolutionary history of the exon structures of bHLH/PAS genes. Taken together, our study revealed the evolutionary model, functional divergence and gene structure conservation of bHLH/PAS genes. These findings provide clues for the functional and evolutionary mechanism of bHLH/PAS genes.

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References

Sailsbery J, Dean R . Accurate discrimination of bHLH domains in plants, animals, and fungi using biologically meaningful sites. BMC Evol Biol. 2012; 12:154. PMC: 3502508. DOI: 10.1186/1471-2148-12-154. View

Gu X . Maximum-likelihood approach for gene family evolution under functional divergence. Mol Biol Evol. 2001; 18(4):453-64. DOI: 10.1093/oxfordjournals.molbev.a003824. View

Reick M, Garcia J, Dudley C, McKnight S . NPAS2: an analog of clock operative in the mammalian forebrain. Science. 2001; 293(5529):506-9. DOI: 10.1126/science.1060699. View

Yang Z . PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol. 2007; 24(8):1586-91. DOI: 10.1093/molbev/msm088. View

Pickard B, Malloy M, Porteous D, Blackwood D, Muir W . Disruption of a brain transcription factor, NPAS3, is associated with schizophrenia and learning disability. Am J Med Genet B Neuropsychiatr Genet. 2005; 136B(1):26-32. DOI: 10.1002/ajmg.b.30204. View

Meyer A, Van de Peer Y . From 2R to 3R: evidence for a fish-specific genome duplication (FSGD). Bioessays. 2005; 27(9):937-45. DOI: 10.1002/bies.20293. View

Gilles-Gonzalez M, Gonzalez G . Signal transduction by heme-containing PAS-domain proteins. J Appl Physiol (1985). 2004; 96(2):774-83. DOI: 10.1152/japplphysiol.00941.2003. View

Vandepoele K, De Vos W, Taylor J, Meyer A, Van de Peer Y . Major events in the genome evolution of vertebrates: paranome age and size differ considerably between ray-finned fishes and land vertebrates. Proc Natl Acad Sci U S A. 2004; 101(6):1638-43. PMC: 341801. DOI: 10.1073/pnas.0307968100. View

Hahn M, Karchner S, Evans B, Franks D, Merson R, Lapseritis J . Unexpected diversity of aryl hydrocarbon receptors in non-mammalian vertebrates: insights from comparative genomics. J Exp Zool A Comp Exp Biol. 2006; 305(9):693-706. DOI: 10.1002/jez.a.323. View

10.

Putnam N, Srivastava M, Hellsten U, Dirks B, Chapman J, Salamov A . Sea anemone genome reveals ancestral eumetazoan gene repertoire and genomic organization. Science. 2007; 317(5834):86-94. DOI: 10.1126/science.1139158. View

11.

Zhou M, Yan J, Ma Z, Zhou Y, Abbood N, Liu J . Comparative and evolutionary analysis of the HES/HEY gene family reveal exon/intron loss and teleost specific duplication events. PLoS One. 2012; 7(7):e40649. PMC: 3396596. DOI: 10.1371/journal.pone.0040649. View

12.

Ploski J, Monsey M, Nguyen T, DiLeone R, Schafe G . The neuronal PAS domain protein 4 (Npas4) is required for new and reactivated fear memories. PLoS One. 2011; 6(8):e23760. PMC: 3161786. DOI: 10.1371/journal.pone.0023760. View

13.

Esser C, Rannug A, Stockinger B . The aryl hydrocarbon receptor in immunity. Trends Immunol. 2009; 30(9):447-54. DOI: 10.1016/j.it.2009.06.005. View

14.

LARKIN M, Blackshields G, Brown N, Chenna R, McGettigan P, McWilliam H . Clustal W and Clustal X version 2.0. Bioinformatics. 2007; 23(21):2947-8. DOI: 10.1093/bioinformatics/btm404. View

15.

Preitner N, Damiola F, Lopez-Molina L, Zakany J, Duboule D, Albrecht U . The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell. 2002; 110(2):251-60. DOI: 10.1016/s0092-8674(02)00825-5. View

16.

Linne V, Eriksson B, Stollewerk A . Single-minded and the evolution of the ventral midline in arthropods. Dev Biol. 2012; 364(1):66-76. DOI: 10.1016/j.ydbio.2012.01.019. View

17.

Kume K, Zylka M, Sriram S, Shearman L, Weaver D, Jin X . mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell. 1999; 98(2):193-205. DOI: 10.1016/s0092-8674(00)81014-4. View

18.

Stevens E, Mezrich J, Bradfield C . The aryl hydrocarbon receptor: a perspective on potential roles in the immune system. Immunology. 2009; 127(3):299-311. PMC: 2712099. DOI: 10.1111/j.1365-2567.2009.03054.x. View

19.

Erbel-Sieler C, Dudley C, Zhou Y, Wu X, Estill S, Han T . Behavioral and regulatory abnormalities in mice deficient in the NPAS1 and NPAS3 transcription factors. Proc Natl Acad Sci U S A. 2004; 101(37):13648-53. PMC: 518807. DOI: 10.1073/pnas.0405310101. View

20.

Hahn M . Distinguishing among evolutionary models for the maintenance of gene duplicates. J Hered. 2009; 100(5):605-17. DOI: 10.1093/jhered/esp047. View