Molecular evolution of methanogens based on their metabolic facets
Received date: 22 Mar 2011
Accepted date: 30 Apr 2011
Published date: 01 Dec 2011
Copyright
The information provided by completely sequenced genomes of methanogens can yield insights into a deeper molecular understanding of evolutionary mechanisms. This review describes the advantages of using metabolic pathways to clarify evolutionary correlation of methanogens with archaea and prokaryotes. Metabolic trees can be used to highlight similarities in metabolic networks related to the biology of methanogens. Metabolic genes are among the most modular in the cell and their genes are expected to travel laterally, even in recent evolution. Phylogenetic analysis of protein superfamilies provides a perspective on the evolutionary history of some key metabolic modules of methanogens. Phage-related genes from distantly related organisms typically invade methanogens by horizontal gene transfer. Metabolic modules in methanogenesis are phylogenetically aligned in closely related methanogens. Reverse order reactions of methanogenesis are achieved in methylotrophic methanogens using metabolic and structural modules of key enzymes. A significant evolutionary process is thought to couple the utilization of heavy metal ions with energetic metabolism in methanogens. Over 30 of methanogens genomes have been sequenced to date, and a variety of databases are being developed that will provide for genome annotation and phylogenomic analysis of methanogens. Into the context of the evolutionary hypothesis, the integration of metabolomic and proteomic data into large-scale mathematical models holds promise for fostering rational strategies for strain improvement.
Key words: methanogens; genomics; metabolic module; phylogeny; protein superfamily; molecular evolution
P. CHELLAPANDI . Molecular evolution of methanogens based on their metabolic facets[J]. Frontiers in Biology, 2011 , 6(6) : 490 -503 . DOI: 10.1007/s11515-011-1154-2
1 |
Aguilar D, Aviles F X, Querol E, Sternberg M J (2004). Analysis of phenetic trees based on metabolic capabilites across the three domains of life. J Mol Biol, 340(3): 491–512
|
2 |
Apic G, Gough J, Teichmann S A (2001). Domain combinations in archaeal, eubacterial and eukaryotic proteomes. J Mol Biol, 310(2): 311–325
|
3 |
Bansal A K (1999). An automated comparative analysis of 17 complete microbial genomes. Bioinformatics, 15(11): 900–908
|
4 |
Bapteste E, Brochier C, Boucher Y (2005). Higher-level classification of the Archaea: evolution of methanogenesis and methanogens. Archaea, 1(5): 353–363
|
5 |
Beja O, Aravind L, Koonin E V, Suzuki M T, Hadd A, Nguyen L P, Jovanovich S B, Gates C M, Feldman R A, Spudich J L, Spudich E N, DeLong E F (2000). Bacterial rhodopsin: evidence for a new type of phototrophy in the sea. Science, 289(5486): 1902–1906
|
6 |
Briones C, Manrubia S C, Lázaro E, Lazcano A, Amils R (2005). Reconstructing evolutionary relationships from functional data: a consistent classification of organisms based on translation inhibition response. Mol Evol Phylogenet, 34(2): 371–381
|
7 |
Brochier C, Forterre P, Gribaldo S (2004). Archaeal phylogeny based on proteins of the transcription and translation machineries: tackling the Methanopyrus kandleri paradox. Genome Biol, 5(3): R17
|
8 |
Brochier C, Forterre P, Gribaldo S (2005). An emerging phylogenetic core of Archaea: phylogenies of transcription and translation machineries converge following addition of new genome sequences. BMC Evol Biol, 5(1): 36
|
9 |
Brown J R, Doolittle W F (1997). Archaea and the prokaryote-to-eukaryote transition. Microbiol Mol Biol Rev, 61(4): 456–502
|
10 |
Brown J R, Douady C J, Italia M J, Marshall W E, Stanhope M J (2001). Universal trees based on large combined protein sequence data sets. Nat Genet, 28(3): 281–285
|
11 |
Bult C J, White O, Olsen G J, Zhou L, Fleischmann R D, Sutton G G, Blake J A, FitzGerald L M, Clayton R A, Gocayne J D, Kerlavage A R, Dougherty B A, Tomb J F, Adams M D, Reich C I, Overbeek R, Kirkness E F, Weinstock K G, Merrick J M, Glodek A, Scott J L, Geoghagen N S M, Venter J C, Fuhrmann J L, Nguyen D, Utterback T R, Kelley J M, Peterson J D, Sadow P W, Hanna M C, Cotton M D, Roberts K M, Hurst M A, Kaine B P, Borodovsky M, Klenk H P, Fraser C M, Smith H O, Woese C R, Venter C J (1996). Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii. Science, 273(5278): 1058–1073
|
12 |
Chellapandi P (2004). Enzymes and microbiological pretreatments of oil industry wastes for biogas production in batch digesters. In: Pathade G R, Goel P K, ed. Biotechnology in Environmental Management, India: ABD Publishers
|
13 |
Chellapandi P (2011). A molecular conception for protein engineering algorithms. Adv Biotech, 10(7): 41–46
|
14 |
Chellapandi P, Dhivya C (2010). Overview of microbial metabolomics: A special insight to cyanobacterial methylotrophy. J Adv Develop Res, 1: 59–73
|
15 |
Chellapandi P, Kalaimathy S (2010). Molecular aspects of β-galactosidase production system in Aspergillus genomes. J Adv Develop Res, 1: 81–89
|
16 |
Chellapandi P, Karthigeyan C, Sivaramakrishnan S (2009). Evolutionary implication of protein secondary structure among archaea and bacteria. Internet J Genomics Proteomics, 4(2)
|
17 |
Chellapandi P, Prabaharan D, Uma L (2008). A preliminary study on co-digestion of ossein factory waste for methane production. EurAsian J Biosci, 2: 110–114
|
18 |
Chellapandi P, Prabaharan D, Uma L (2010a). Evaluation of methanogenic activity of biogas plant slurry for monitoring codigestion of ossein factory wastes and cyanobacterial biomass. Appl Biochem Biotechnol, 162(2): 524–535
|
19 |
Chellapandi P, Ranjani J (2011). Molecular machinery of CRISPR-CAS system – RNA mediated defense pathway in Prokaryotes. Asian J Biotechnol, 3(4): 329–336
|
20 |
Chellapandi P, Sivaramakrishnan S, Viswanathan M B (2010b). Systems biotechnology: An emerging trend in metabolic engineering of industrial microorganisms. J Comput Sci Syst Biol, 3(2): 43–49
|
21 |
Chellapandi P, Sivaramakrishnan S (2011). In: Baginski S J, ed. Protein superfamilies based phylogenomic analysis of archaeal domain. Biochemistry Research Updates, USA: Nova Science Publications, Inc.
|
22 |
Chellapandi P, Suman L S, Sivaramakrishnan S (2007). Biomethanation of fungal predigested caster seed cake in acclimatized seed. Biotechnol: An Indian Journal, 1: 19–24
|
23 |
Chistoserdova L, Vorholt J A, Thauer R K, Lidstrom M E (1998). C1 transfer enzymes and coenzymes linking methylotrophic bacteria and methanogenic Archaea. Science, 281(5373): 99–102
|
24 |
Corbett K D, Berger J M (2003). Structure of the topoisomerase VI-B subunit: implications for type II topoisomerase mechanism and evolution. EMBO J, 22(1): 151–163
|
25 |
Daiyasu H, Kuma K, Yokoi T, Morii H, Koga Y, Toh H (2005). A study of archaeal enzymes involved in polar lipid synthesis linking amino acid sequence information, genomic contexts and lipid composition. Archaea, 1(6): 399–410
|
26 |
Daubin V, Gouy M, Perrière G (2002). A phylogenomic approach to bacterial phylogeny: evidence of a core of genes sharing a common history. Genome Res, 12(7): 1080–1090
|
27 |
Deppenmeier U, Johann A, Hartsch T, Merkl R, Schmitz R A, Martinez-Arias R, Henne A, Wiezer A, Bäumer S, Jacobi C, Brüggemann H, Lienard T, Christmann A, Bömeke M, Steckel S, Bhattacharyya A, Lykidis A, Overbeek R, Klenk H P, Gunsalus R P, Fritz H J, Gottschalk G (2002). The genome of Methanosarcina mazei: evidence for lateral gene transfer between bacteria and archaea. J Mol Microbiol Biotechnol, 4(4): 453–461
|
28 |
Doolittle R F, Feng D F, Tsang S, Cho G, Little E (1996). Determining divergence times of the major kingdoms of living organisms with a protein clock. Science, 271(5248): 470–477
|
29 |
Downs D M (2006). Understanding microbial metabolism. Annu Rev Microbiol, 60(1): 533–559
|
30 |
Dvornyk V, Vinogradova O, Nevo E (2003). Origin and evolution of circadian clock genes in prokaryotes. Proc Natl Acad Sci U S A, 100(5): 2495–2500
|
31 |
Edgell D R, Doolittle W F (1997). Archaea and the origin(s) of DNA replication proteins. Cell, 89(7): 995–998
|
32 |
Eisen J A (1998). Phylogenomics: improving functional predictions for uncharacterized genes by evolutionary analysis. Genome Res, 8(3): 163–167
|
33 |
Feng D F, Cho G, Doolittle R F (1997). Determining divergence times with a protein clock: update and reevaluation. Proc Natl Acad Sci U S A, 94(24): 13028–13033
|
34 |
Fitz-Gibbon S T, House C H (1999). Whole genome-based phylogenetic analysis of free-living microorganisms. Nucleic Acids Res, 27(21): 4218–4222
|
35 |
Forst C V, Schulten K (1999). Evolution of metabolisms: a new method for the comparison of metabolic pathways using genomics information. J Comput Biol, 6(3–4): 343–360
|
36 |
Forst C V, Schulten K (2001). Phylogenetic analysis of metabolic pathways. J Mol Evol, 52(6): 471–489
|
37 |
Fournier G P, Gogarten J P (2008). Evolution of acetoclastic methanogenesis in Methanosarcina via horizontal gene transfer from cellulolytic Clostridia. J Bacteriol, 190(3): 1124–1127
|
38 |
Friedrich M W (2005). Methyl-coenzyme M reductase genes: unique functional markers for methanogenic and anaerobic methane-oxidizing Archaea. Methods Enzymol, 397: 428–442
|
39 |
Frigaard N U, Martinez A, Mincer T J, DeLong E F (2006). Proteorhodopsin lateral gene transfer between marine planktonic Bacteria and Archaea. Nature, 439(7078): 847–850
|
40 |
Gaasterland T, Ragan M A (1998). Constructing multigenome views of whole microbial genomes. Microb Comp Genomics, 3(3): 177–192
|
41 |
Gadelle D, Filée J, Buhler C, Forterre P (2003). Phylogenomics of type II DNA topoisomerases. Bioessays, 25(3): 232–242
|
42 |
Galagan J E C, Nusbaum C, Roy A, Endrizzi M G, Macdonald P, FitzHugh W, Calvo S, Engels R, Smirnov S, Atnoor D, Brown A, Allen N, Naylor J, Stange-Thomann N, DeArellano K, Johnson R, Linton L, McEwan P, McKernan K, Talamas J, Tirrell A, Ye W, Zimmer A, Barber R D, Cann I, Graham D E, Grahame D A, Guss A M, Hedderich R, Ingram-Smith C, Kuettner H C, Krzycki J A, Leigh J A, Li W, Liu J, Mukhopadhyay B, Reeve J N, Smith K, Springer T A, Umayam L A, White O, White R H, Conway de Macario E, Ferry J G, Jarrell K F, Jing H, Macario A J, Paulsen I, Pritchett M, Sowers K R, Swanson R V, Zinder S H, Lander E, Metcalf W W, Birren B (2002). The genome of M. acetivorans reveals extensive metabolic and physiological diversity. Genome Res, 12(4): 532–542
|
43 |
Graham D E, Overbeek R, Olsen G J, Woese C R (2000). An archaeal genomic signature. Proc Natl Acad Sci U S A, 97(7): 3304–3308
|
44 |
Hallam S J, Girguis P R, Preston C M, Richardson P M, DeLong E F (2003). Identification of methyl coenzyme M reductase A (mcrA) genes associated with methane-oxidizing archaea. Appl Environ Microbiol, 69(9): 5483–5491
|
45 |
Hallam S J, Putnam N, Preston C M, Detter J C, Rokhsar D, Richardson P M, DeLong E F (2004). Reverse methanogenesis: testing the hypothesis with environmental genomics. Science, 305(5689): 1457–1462
|
46 |
Hartzell P L, Zvilius G, Escalante-Semerena J C, Donnelly M I (1985). Coenzyme F420 dependence of the methylenetetrahydromethanopterin dehydrogenase of Methanobacterium thermoautotrophicum. Biochem Biophys Res Commun, 133(3): 884–890
|
47 |
Hedges S B (2002). The origin and evolution of model organisms. Nat Rev Genet, 3(11): 838–849
|
48 |
Hedges S B, Kumar S (2004). Precision of molecular time estimates. Trends Genet, 20(5): 242–247
|
49 |
Heymans M, Singh A K (2003). Deriving phylogenetic trees from the similarity analysis of metabolic pathways. Bioinformatics, 19(Suppl 1): i138–i146
|
50 |
Hong S H, Kim T Y, Lee S Y (2004). Phylogenetic analysis based on genome-scale metabolic pathway reaction content. Appl Microbiol Biotechnol, 65(2): 203–210
|
51 |
Huynen M A, Bork P (1998). Measuring genome evolution. Proc Natl Acad Sci U S A, 95(11): 5849–5856
|
52 |
John U, Fensome R A, Medlin L K (2003). The application of a molecular clock based on molecular sequences and the fossil record to explain biogeographic distributions within the Alexandrium tamarense “species complex” (Dinophyceae). Mol Biol Evol, 20(7): 1015–1027
|
53 |
Johnson E F, Mukhopadhyay B (2005). A new type of sulfite reductase, a novel coenzyme F420-dependent enzyme, from the methanarchaeon Methanocaldococcus jannaschii. J Biol Chem, 280(46): 38776–38786
|
54 |
Johnson E F, Mukhopadhyay B (2007). A novel coenzyme F420 dependent sulfite reductase and a small sulfite reductase in methanogenic archaea. In: Dahl C, Friedrich C G, eds. Microbial Sulfur Metabolism, Berlin: Springer, 202–216
|
55 |
Kalyuzhnaya M G, Bowerman S, Nercessian O, Lidstrom M E, Chistoserdova L (2005). Highly divergent genes for methanopterin-linked C1 transfer reactions in Lake Washington, assessed via metagenomic analysis and mRNA detection. Appl Environ Microbiol, 71(12): 8846–8854
|
56 |
Karthigeyan C, Sivaramakrishnan S, Chellapandi P (2007). Phylogenomic analysis of archaeal domain. Bioinformatics Trends, 2(1): 37–55
|
57 |
Kato N, Yurimoto H, Thauer R K (2006). The physiological role of the ribulose monophosphate pathway in bacteria and archaea. Biosci Biotechnol Biochem, 70(1): 10–21
|
58 |
Klein M, Friedrich M, Roger A J, Hugenholtz P, Fishbain S, Abicht H, Blackall L L, Stahl D A, Wagner M (2001). Multiple lateral transfers of dissimilatory sulfite reductase genes between major lineages of sulfate-reducing prokaryotes. J Bacteriol, 183(20): 6028–6035
|
59 |
Klenk H P, Clayton R A, Tomb J F, White O, Nelson K E, Ketchum K A, Dodson R J, Gwinn M, Hickey E K, Peterson J D, Richardson D L, Kerlavage A R, Graham D E, Kyrpides N C, Fleischmann R D, Quackenbush J, Lee N H, Sutton G G, Gill S, Kirkness E F, Dougherty B A, McKenney K, Adams M D, Loftus B, Peterson S, Reich C I, McNeil L K, Badger J H, Glodek A, Zhou L, Overbeek R, Gocayne J D, Weidman J F, McDonald L, Utterback T, Cotton M D, Spriggs T, Artiach P, Kaine B P, Sykes S M, Sadow P W, D’Andrea K P, Bowman C, Fujii C, Garland S A, Mason T M, Olsen G J, Fraser C M, Smith H O, Woese C R, Venter J C (1997). The complete genome sequence of the hyperthermophilic, sulphate-reducing archaeon Archaeoglobus fulgidus. Nature, 390(6658): 364–370
|
60 |
Koonin E V (2005). Orthologs, paralogs, and evolutionary genomics. Annu Rev Genet, 39(1): 309–338
|
61 |
Koonin E V, Mushegian A R, Galperin M Y, Walker D R (1997). Comparison of archaeal and bacterial genomes: computer analysis of protein sequences predicts novel functions and suggests a chimeric origin for the archaea. Mol Microbiol, 25(4): 619–637
|
62 |
Koonin E V, Wolf Y I (2008). Genomics of bacteria and archaea: the emerging dynamic view of the prokaryotic world. Nucleic Acids Res, 36(21): 6688–6719
|
63 |
Koonin E V, Wolf Y I, Kondrashov A S, Aravind L (2000). Bacterial homologs of the small subunit of eukaryotic DNA primase. J Mol Microbiol Biotechnol, 2(4): 509–512
|
64 |
Kyrpides N C, Olsen G J, Klenk H P, White O, Woese C R (1996). Methanococcus jannaschii genome: revisited. Microb Comp Genomics, 1(4): 329–338
|
65 |
Lake J A, Clark M W, Henderson E, Fay S P, Oakes M, Scheinman A, Thornber J P, Mah R A (1985). Eubacteria, halobacteria, and the origin of photosynthesis: the photocytes. Proc Natl Acad Sci U S A, 82(11): 3716–3720
|
66 |
Ma H W, Zeng A P (2004). Phylogenetic comparison of metabolic capacities of organisms at genome level. Mol Phylogenet Evol, 31(1): 204–213
|
67 |
Macario A J, Lange M, Ahring B K, Conway de Macario E (1999). Stress genes and proteins in the archaea. Microbiol Mol Biol Rev, 63(4): 923–967
|
68 |
Makarova K S, Koonin E V (2003). Comparative genomics of Archaea: how much have we learned in six years, and what’s next? Genome Biol, 4(8): 115
|
69 |
Makarova K S, Koonin E V (2007). Evolutionary genomics of lactic acid bacteria. J Bacteriol, 189(4): 1199–1208
|
70 |
Masinovsky Z, Lozovaya G I, Sivash A A (1992). Some aspects of the early evolution of photosynthesis. Adv Space Res, 12(4): 199–205
|
71 |
Min H, Zinder S H (1989). Kinetics of acetate utilization by two thermophilic acetotrophic methanogens: Methanosarcina sp. strain CALS-1 and Methanothrix sp. strain CALS-1. Appl Environ Microbiol, 55(2): 488–491
|
72 |
Morii H, Kiyonari S, Ishino Y, Koga Y (2009). A novel biosynthetic pathway of archaetidyl-myo-inositol via archaetidyl-myo-inositol phosphate from CDP-archaeol and D-glucose 6-phosphate in methanoarchaeon Methanothermobacter thermautotrophicus cells. J Biol Chem, 284(45): 30766–30774
|
73 |
Müller V, Spanheimer R, Santos H (2005). Stress response by solute accumulation in archaea. Curr Opin Microbiol, 8(6): 729–736
|
74 |
Nielsen J, Oliver S (2005). The next wave in metabolome analysis. Trends Biotechnol, 23(11): 544–546
|
75 |
Nolling J, Elfner A, Palmer J R, Steigerwald V J, Pihl T D, Lake J A, Reeve J N (1996). Phylogeny of Methanopyrus kandleri based on methyl coenzyme M reductase operons. Int J Syst Bacteriol, 46(4): 1170–1173
|
76 |
Olsen G J, Woese C R (1997). Archaeal genomics: an overview. Cell, 89(7): 991–994
|
77 |
Pagel M (1999). Inferring the historical patterns of biological evolution. Nature, 401(6756): 877–884
|
78 |
Patel C N, Chellapandi P (2008). Anaerobic digestion of cotton seed cake using developed mixed consortia. Electronic J Environ Agri Food Chem, 7: 3035–3046
|
79 |
Ponomarev V A, Makarova K S, Aravind L, Koonin E V (2003). Gene duplication with displacement and rearrangement: origin of the bacterial replication protein PriB from the single-stranded DNA-binding protein Ssb. J Mol Microbiol Biotechnol, 5(4): 225–229
|
80 |
Razia M, Karthik Raja R, Padmanaban K, Sivaramakrishnan S, Chellapandi P (2010). Phylogenetic approach for assigning function of hypothetical proteins in Photorhabdus luminescens subsp. laumondii T101 genome. J Comput Sci Syst Biol, 3(1): 21–29
|
81 |
Razia M, Padmanaban K, Karthick Raja R, Chellapandi P, Sivaramakrishnan S (2011). 16S rDNA-based phylogeny of non-symbiotic bacteria associating entomopathogenic nematode from infected insect cadavers. Genomics Proteomics Bioinformatics (In press)
|
82 |
Schmidt S, Christen P, Kiefer P, Vorholt J A (2010). Functional investigation of methanol dehydrogenase-like protein XoxF in Methylobacterium extorquens AM1. Microbiology, 156(Pt 8): 2575–2586
|
83 |
Schopf J W (2006). Fossil evidence of Archaean life. Philos Trans R Soc Lond B Biol Sci, 361(1470): 869–885
|
84 |
Snel B, Bork P, Huynen M A (1999). Genome phylogeny based on gene content. Nat Genet, 21(1): 108–110
|
85 |
Snel B, Bork P, Huynen M A (2002). Genomes in flux: the evolution of archaeal and proteobacterial gene content. Genome Res, 12(1): 17–25
|
86 |
Tatusov R L, Koonin E V, Lipman D J (1997). A genomic perspective on protein families. Science, 278(5338): 631–637
|
87 |
Tekaia F, Lazcano A, Dujon B (1999). The genomic tree as revealed from whole proteome comparisons. Genome Res, 9(6): 550–557
|
88 |
Thauer R K (1998). Biochemistry of methanogenesis: a tribute to Marjory Stephenson. 1998 Marjory Stephenson Prize Lecture. Microbiology, 144(Pt 9): 2377–2406
|
89 |
Thauer R K, Bonacker L G (1994). Biosynthesis of coenzyme F430, a nickel porphinoid involved in methanogenesis. Ciba Found Symp, 180: 210–222
|
90 |
Thauer R K, Kaster A K, Seedorf H, Buckel W, Hedderich R (2008). Methanogenic archaea: ecologically relevant differences in energy conservation. Nat Rev Microbiol, 6(8): 579–591
|
91 |
van Hoek A H A M, van Alen T A, Sprakel V S I, Leunissen J A, Brigge T, Vogels G D, Hackstein J H P (2000). Multiple acquisition of methanogenic archaeal symbionts by anaerobic ciliates. Mol Biol Evol, 17(2): 251–258
|
92 |
Vedhagiri K, Natarajaseenivasan K, Chellapandi P, Prabhakaran S G, Selvin J, Sharma S, Vijayachari P (2009). Evolutionary implication of outer membrane lipoprotein-encoding genes ompL1, UpL32 and lipL41 of pathogenic Leptospira species. Genomics Proteomics Bioinformatics, 7(3): 96–106
|
93 |
Verhees C H, Kengen S W, Tuininga J E, Schut G J, Adams M W W, de VOS W M, van der Oost J (2003). The unique features of glycolytic pathways in Archaea. Biochem J, 375(Pt 2): 231–246
|
94 |
Vorholt J A, Marx C J, Lidstrom M E, Thauer R K (2000). Novel formaldehyde-activating enzyme in Methylobacterium extorquens AM1 required for growth on methanol. J Bacteriol, 182(23): 6645–6650
|
95 |
Vothknecht U C, Tumbula D L (1999). Archaea: from genomics to physiology and the origin of life. Trends Cell Biol, 9(4): 159–161
|
96 |
Waters E, Hohn M J, Ahel I, Graham D E, Adams M D, Barnstead M, Beeson K Y, Bibbs L, Bolanos R, Keller M, Kretz K, Lin X, Mathur E, Ni J, Podar M, Richardson T, Sutton G G, Simon M, Söll D, Stetter K O, Short J M, Noordewier M (2003). The genome of Nanoarchaeum equitans: insights into early archaeal evolution and derived parasitism. Proc Natl Acad Sci U S A, 100(22): 12984–12988
|
97 |
Wilson R C, Bohlen C J, Foster M P, Bell C E (2006). Structure of Pfu Pop5, an archaeal RNase P protein. Proc Natl Acad Sci U S A, 103(4): 873–878
|
98 |
Woese C R, Kandler O, Wheelis M L (1990). Towards a natural system of organisms: proposal for the domains Archaea, Bacteria, and Eucarya. Proc Natl Acad Sci U S A, 87(12): 4576–4579
|
99 |
Woese C R, Magrum L J, Fox G E (1978). Archaebacteria. J Mol Evol, 11(3): 245–251
|
/
〈 | 〉 |