title: Dark matter in archaeal genomes: a rich source of novel mobile elements, defense systems and secretory complexes.
abstract: Microbial genomes encompass a sizable fraction of poorly characterized, narrowly spread fast-evolving genes. Using sensitive methods for sequences comparison and protein structure prediction, we performed a detailed comparative analysis of clusters of such genes, which we denote "dark matter islands", in archaeal genomes. The dark matter islands comprise up to 20% of archaeal genomes and show remarkable heterogeneity and diversity. Nevertheless, three classes of entities are common in these genomic loci: (a) integrated viral genomes and other mobile elements; (b) defense systems, and (c) secretory and other membrane-associated systems. The dark matter islands in the genome of thermophiles and mesophiles show similar general trends of gene content, but thermophiles are substantially enriched in predicted membrane proteins whereas mesophiles have a greater proportion of recognizable mobile elements. Based on this analysis, we predict the existence of several novel groups of viruses and mobile elements, previously unnoticed variants of CRISPR-Cas immune systems, and new secretory systems that might be involved in stress response, intermicrobial conflicts and biogenesis of novel, uncharacterized membrane structures.
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD, 20894, USA.
authors.forename: Kira S
authors.initials: KS
authors.lastname: Makarova
authors.forename: Yuri I
authors.initials: YI
authors.lastname: Wolf
authors.forename: Patrick
authors.initials: P
authors.lastname: Forterre
authors.forename: David
authors.initials: D
authors.lastname: Prangishvili
authors.forename: Mart
authors.initials: M
authors.lastname: Krupovic
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Koonin
mesh_terms: D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D001105:Archaea / Q000235:genetics* / Q000378:metabolism; D019843:Archaeal Proteins / Q000235:genetics*; D020745:Genome, Archaeal; D006358:Hot Temperature; D020071:Interspersed Repetitive Sequences; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data
chemical_list: D019843:Archaeal Proteins; D008565:Membrane Proteins
references.citation: J Mol Biol. 1999 Sep 17;292(2):195-202
references.pmid: 10493868
references.citation: Microbiol Mol Biol Rev. 2009 Dec;73(4):775-808
references.pmid: 19946141
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D205-10
references.pmid: 18984618
references.citation: J Bacteriol. 2011 Oct;193(19):5412-9
references.pmid: 21784945
references.citation: Structure. 2013 May 7;21(5):718-26
references.pmid: 23623731
references.citation: Nat Struct Mol Biol. 2004 Feb;11(2):157-62
references.pmid: 14730355
references.citation: Front Microbiol. 2012 Jun 05;3:200
references.pmid: 22679442
references.citation: Nat Rev Genet. 2014 May;15(5):321-34
references.pmid: 24690881
references.citation: Mol Cell. 2013 Sep 12;51(5):594-605
references.pmid: 24034694
references.citation: Comp Funct Genomics. 2003;4(4):432-41
references.pmid: 18629076
references.citation: Biochem Soc Trans. 2011 Jan;39(1):82-8
references.pmid: 21265751
references.citation: Virus Res. 2012 Feb;163(2):454-60
references.pmid: 22108584
references.citation: Genome Res. 2004 Jun;14(6):1036-42
references.pmid: 15173110
references.citation: Biol Direct. 2012 Dec 14;7:46
references.pmid: 23241446
references.citation: RNA Biol. 2013 May;10(5):679-86
references.pmid: 23439366
references.citation: Mol Gen Genet. 1987 Sep;209(2):270-5
references.pmid: 17191342
references.citation: Annu Rev Food Sci Technol. 2012;3:143-62
references.pmid: 22224556
references.citation: Trends Microbiol. 2012 Jul;20(7):307-12
references.pmid: 22613456
references.citation: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W244-8
references.pmid: 15980461
references.citation: Biol Direct. 2006 Sep 19;1:29
references.pmid: 16984643
references.citation: Nucleic Acids Res. 2013 Apr;41(8):4360-77
references.pmid: 23470997
references.citation: Biochem Soc Trans. 2011 Jan;39(1):104-6
references.pmid: 21265755
references.citation: Environ Microbiol. 2009 Nov;11(11):2849-62
references.pmid: 19638177
references.citation: Bioinformatics. 2012 Apr 15;28(8):1166-7
references.pmid: 22368248
references.citation: Nat Methods. 2011 Sep 29;8(10):785-6
references.pmid: 21959131
references.citation: Genome Res. 2000 Aug;10(8):1074-7
references.pmid: 10958625
references.citation: Nat Rev Genet. 2010 Mar;11(3):181-90
references.pmid: 20125085
references.citation: Nat Biotechnol. 2005 Oct;23(10):1269-73
references.pmid: 16116419
references.citation: Ann N Y Acad Sci. 1999 May 18;870:293-300
references.pmid: 10415491
references.citation: J Mol Biol. 2005 May 6;348(3):617-29
references.pmid: 15826659
references.citation: Genome Biol. 2009;10(6):R65
references.pmid: 19531232
references.citation: J Virol. 2013 May;87(10):5926-36
references.pmid: 23514883
references.citation: PLoS One. 2013;8(1):e49044
references.pmid: 23326305
references.citation: Biochem Soc Trans. 2013 Feb 1;41(1):443-50
references.pmid: 23356326
references.citation: Curr Opin Genet Dev. 1997 Dec;7(6):757-63
references.pmid: 9468784
references.citation: Virology. 2008 May 25;375(1):292-300
references.pmid: 18308362
references.citation: Front Microbiol. 2014 Mar 12;5:84
references.pmid: 24659986
references.citation: J Bacteriol. 2013 Sep;195(18):4195-201
references.pmid: 23852869
references.citation: Nat Biotechnol. 2000 Jun;18(6):609-13
references.pmid: 10835597
references.citation: J Bacteriol. 2011 Nov;193(21):6039-56
references.pmid: 21908672
references.citation: Biochem Soc Trans. 2004 Apr;32(Pt 2):222-6
references.pmid: 15046576
references.citation: Mol Microbiol. 1999 Oct;34(2):217-26
references.pmid: 10564466
references.citation: Biochem Soc Trans. 2013 Dec;41(6):1392-400
references.pmid: 24256226
references.citation: PLoS One. 2011 May 10;6(5):e19893
references.pmid: 21572966
references.citation: Nucleic Acids Res. 2005 Jul 15;33(12):3875-96
references.pmid: 16027112
references.citation: Extremophiles. 2014 May;18(3):473-89
references.pmid: 24562787
references.citation: Mol Biol Evol. 2013 Feb;30(2):315-31
references.pmid: 22977114
references.citation: Nat Rev Microbiol. 2008 Dec;6(12):941-8
references.pmid: 19008892
references.citation: Nucleic Acids Res. 2014 Apr;42(6):3707-19
references.pmid: 24445805
references.citation: Biol Direct. 2006 Mar 16;1:7
references.pmid: 16545108
references.citation: J Virol. 2014 Feb;88(4):2354-8
references.pmid: 24335300
references.citation: J Bacteriol. 2011 Feb;193(4):804-14
references.pmid: 21075925
references.citation: Mol Microbiol. 1997 Apr;24(2):241-8
references.pmid: 9159511
references.citation: J Mol Biol. 2001 Jan 19;305(3):567-80
references.pmid: 11152613
references.citation: Biol Direct. 2011 Jul 14;6:38
references.pmid: 21756346
references.citation: FEBS J. 2008 Sep;275(17):4389-402
references.pmid: 18671730
references.citation: Nucleic Acids Res. 2008 Dec;36(21):6688-719
references.pmid: 18948295
references.citation: Annu Rev Microbiol. 2013;67:565-85
references.pmid: 24024638
references.citation: Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
references.pmid: 9254694
references.citation: Nature. 2002 Jun 6;417(6889):656-9
references.pmid: 12050668
references.citation: Res Microbiol. 2012 Nov-Dec;163(9-10):630-44
references.pmid: 23146836
references.citation: Biol Direct. 2009 Jun 03;4:19
references.pmid: 19493340
references.citation: Arch Virol. 2014 Jun;159(6):1541-54
references.pmid: 24395078
references.citation: Nucleic Acids Res. 2006;34(22):6505-20
references.pmid: 17130173
references.citation: Nat Rev Microbiol. 2011 Jun;9(6):467-77
references.pmid: 21552286
references.citation: Biol Direct. 2007 Nov 27;2:33
references.pmid: 18042280
references.citation: Nature. 2014 Mar 13;507(7491):258-261
references.pmid: 24531762
references.citation: Environ Microbiol. 2012 Feb;14(2):503-16
references.pmid: 22151304
references.citation: BMC Evol Biol. 2006 Aug 16;6:63
references.pmid: 16914045
references.citation: Mol Biol Evol. 2010 Dec;27(12):2716-32
references.pmid: 20581330
references.citation: Nucleic Acids Res. 2004 Oct 05;32(17):5260-79
references.pmid: 15466593
references.citation: Nucleic Acids Res. 2008 Apr;36(7):2295-300
references.pmid: 18287115