Genomic Insights into Evolution of AdpA Family Master Regulators of Morphological Differentiation and Secondary Metabolism in Streptomyces
The AdpA protein from a streptomycin producer Streptomyces griseus is a founding member of the AdpA family of pleiotropic regulators, known to be ubiquitously present in streptomycetes. Functional genomic approaches revealed a huge number of AdpA targets, leading to the claim that the AdpA regulon is the largest one in bacteria. The expression of adpA is limited at the level of translation of the rare leucyl UUA codon. All known properties of AdpA regulators were discovered on a few streptomycete strains. There are open questions about the true abundance and diversity of AdpA across actinobacterial taxa (and beyond) and about the possible evolutionary forces that shape the AdpA orthologous group in Streptomyces. Here we show that, with respect to the TTA codon, streptomycete adpA is more diverse than has been previously thought, as the genes differ in presence/position of this codon. Reciprocal best hits to AdpA can be found in many actinobacterial orders, with a domain organization resembling that of the prototypical AdpA, but other configurations also exist. Diversifying positive selection was detected within the DNA-binding (AraC) domain in adpA of Streptomyces origin, most likely affecting residues enabling AdpA to recognize a degenerate operator. Sequence coding for putative glutamine amidotransferase (GATase-1) domain also shows signs of positive selection. The two-domain organization of AdpA most likely arose from a fusion of genes encoding separate GATase-1 and AraC domains. Indeed, we show that the AraC domain retains a biological function in the absence of the GATase-1 part. We suggest that acquisition of the regulatory role by TTA codon is a relatively recent event in the evolution of AdpA, which coincided with the rise of the Streptomycetales clade and, at present, is under relaxed selective constraints. Further experimental scrutiny of our findings is invited, which should provide new insights into the evolution and prospects for engineering of an AdpA-centered regulatory network.
KeywordsAdpA Rare codons Actinobacteria Positive and negative selection Evolutionary analysis
The work was supported by grant BG-41Nr from the Ministry of Education and Science of Ukraine (to B.O.).
- Akaike H (1973) Information theory and an extension of the maximum likelihood principle. In: Petrov BN, Csaki F (eds) Second international symposium on information theory. Akademiai Kiado, Budapest, pp 267–281Google Scholar
- Higo A, Hara H, Horinouchi S, Ohnishi Y (2012) Genome-wide distribution of AdpA, a global regulator for secondary metabolism and morphological differentiation in streptomyces, revealed the extent and complexity of the AdpA regulatory network. DNA Res 19(3):259–273CrossRefPubMedPubMedCentralGoogle Scholar
- Jolley KA, Bliss CM, Bennett JS, Bratcher HB, Brehony C, Colles FM, Wimalarathna H, Harrison OB, Sheppard SK, Cody AJ, Maiden MCJ (2012) Ribosomal multilocus sequence typing: universal characterization of bacteria from domain to strain. Microbiology 158(4):1005–1015CrossRefPubMedPubMedCentralGoogle Scholar
- Kieser T, Bibb MJ, Buttner MJ, Chater KF, Hopwood DA (2000) Practical streptomyces genetics. John Innes Foundation, NorwichGoogle Scholar
- Marchler-Bauer A, Lu S, Anderson JB, Chitsaz F, Derbyshire MK, DeWeese-Scott C, Fong JH, Geer LY, Geer RC, Gonzales NR, Gwadz M, Hurwitz DI, Jackson JD, Ke Z, Lanczycki CJ, Lu F, Marchler GH, Mullokandov M, Omelchenko MV, Robertson CL, Song JS, Thanki N, Yamashita RA, Zhang D, Zhang N, Zheng C, Bryant SH (2011) CDD: a conserved domain database for the functional annotation of proteins. Nucleic Acids Res 39(Suppl 1):225–229CrossRefGoogle Scholar
- Ostash B, Yushchuk O, Tistechok S, Mutenko H, Horbal L, Muryn A, Dacyuk Y, Kalinowski J, Luzhetskyy A, Fedorenko V (2015) The adpA-like regulatory gene from Actinoplanes teichomyceticus: in silico analysis and heterologous expression. World J Microbiol Biotechnol 31(8):1297–1301CrossRefPubMedGoogle Scholar
- Tanabe M, Kanehisa M (2012) Using the KEGG database resource. Curr Protoc Bioinform 38:1.12:1.12.1–1.12.43Google Scholar
- Wattam AR, Abraham D, Dalay O, Disz TL, Driscoll T, Gabbard JL, Gillespie JJ, Gough R, Hix D, Kenyon R, Machi D, Mao C, Nordberg EK, Olson R, Overbeek R, Pusch GD, Shukla M, Schulman J, Stevens RL, Sullivan DE, Vonstein V, Warren A, Will R, Wilson MJ, Yoo HS, Zhang C, Zhang Y, Sobral BW (2014) PATRIC, the bacterial bioinformatics database and analysis resource. Nucleic Acids Res 42(D1):581–591CrossRefGoogle Scholar
- Yao MD, Ohtsuka J, Nagata K, Miyazono KI, Zhi Y, Ohnishi Y, Tanokura M (2013) Complex structure of the DNA-binding domain of AdpA, the global transcription factor in Streptomyces griseus, and a target duplex DNA reveals the structural basis of its tolerant DNA sequence specificity. J Biol Chem 288(43):31019–31029CrossRefPubMedGoogle Scholar