Editing Methanogen (section)

==Comparative genomics and molecular signatures==

Comparative proteomic analysis has led to the identification of 31 signature proteins which are specific for methanogens (also known as Methanoarchaeota). Most of these proteins are related to methanogenesis, and they could serve as potential molecular markers for methanogens. Additionally, 10 proteins found in all methanogens, which are shared by ''[[Archaeoglobus]]'', suggest that these two groups are related. In phylogenetic trees, methanogens are not monophyletic and they are generally split into three clades. Hence, the unique shared presence of large numbers of proteins by all methanogens could be due to lateral gene transfers.<ref>{{Cite journal|last1=Gao|first1=Beile|last2=Gupta|first2=Radhey S|date=2007|title=Phylogenomic analysis of proteins that are distinctive of Archaea and its main subgroups and the origin of methanogenesis|journal=BMC Genomics|volume=8|issue=1|pages=86|doi=10.1186/1471-2164-8-86|pmc=1852104|pmid=17394648 |doi-access=free }}</ref> Additionally, more recent novel proteins associated with sulfide trafficking have been linked to methanogen archaea.<ref>{{Cite journal|last1=Rauch|first1=Benjamin Julius|last2=Gustafson|first2=Andrew|last3=Perona|first3=John J.|date=December 2014|title=Novel proteins for homocysteine biosynthesis in anaerobic microorganisms|journal=Molecular Microbiology|language=en|volume=94|issue=6|pages=1330–1342|doi=10.1111/mmi.12832|pmid=25315403|issn=0950-382X|doi-access=free}}</ref> More proteomic analysis is needed to further differentiate specific genera within the methanogen class and reveal novel pathways for methanogenic metabolism.{{cn|date=March 2025}}

Modern DNA or RNA sequencing approaches has elucidated several genomic markers specific to several groups of methanogens. One such finding isolated nine methanogens from genus Methanoculleus and found that there were at least 2 trehalose synthases genes that were found in all nine genomes.<ref>{{Cite journal|last1=Chen|first1=Sheng-Chung|last2=Weng|first2=Chieh-Yin|last3=Lai|first3=Mei-Chin|last4=Tamaki|first4=Hideyuki|last5=Narihiro|first5=Takashi|date=October 2019|title=Comparative genomic analyses reveal trehalose synthase genes as the signature in genus Methanoculleus|journal=Marine Genomics|language=en|volume=47|pages=100673|doi=10.1016/j.margen.2019.03.008|pmid=30935830|bibcode=2019MarGn..4700673C |s2cid=91188321 |doi-access=}}</ref> Thus far, the gene has been observed only in this genus, therefore it can be used as a marker to identify the archaea Methanoculleus. As sequencing techniques progress and databases become populated with an abundance of genomic data, a greater number of strains and traits can be identified, but many genera have remained understudied. For example, halophilic methanogens are potentially important microbes for carbon cycling in coastal wetland ecosystems but seem to be greatly understudied. One recent publication isolated a novel strain from genus ''Methanohalophilus'' which resides in sulfide-rich seawater. Interestingly, they have isolated several portions of this strain's genome that are different from other isolated strains of this genus (''Methanohalophilus mahii'', ''Methanohalophilus halophilus'', ''Methanohalophilus portucalensis'', ''Methanohalophilus euhalbius''). Some differences include a highly conserved genome, sulfur and glycogen metabolisms and viral resistance.<ref>{{Cite journal|last1=Guan|first1=Yue|last2=Ngugi|first2=David K.|last3=Vinu|first3=Manikandan|last4=Blom|first4=Jochen|last5=Alam|first5=Intikhab|last6=Guillot|first6=Sylvain|last7=Ferry|first7=James G.|last8=Stingl|first8=Ulrich|date=2019-04-24|title=Comparative Genomics of the Genus Methanohalophilus, Including a Newly Isolated Strain From Kebrit Deep in the Red Sea|journal=Frontiers in Microbiology|volume=10|pages=839|doi=10.3389/fmicb.2019.00839|issn=1664-302X|pmc=6491703|pmid=31068917|doi-access=free}}</ref> Genomic markers consistent with the microbes environment have been observed in many other cases. One such study found that methane producing archaea found in hydraulic fracturing zones had genomes which varied with vertical depth. Subsurface and surface genomes varied along with the constraints found in individual depth zones, though fine-scale diversity was also found in this study.<ref>{{Cite journal|last1=Borton|first1=Mikayla A.|last2=Daly|first2=Rebecca A.|last3=O'Banion|first3=Bridget|last4=Hoyt|first4=David W.|last5=Marcus|first5=Daniel N.|last6=Welch|first6=Susan|last7=Hastings|first7=Sybille S.|last8=Meulia|first8=Tea|last9=Wolfe|first9=Richard A.|last10=Booker|first10=Anne E.|last11=Sharma|first11=Shikha|date=December 2018|title=Comparative genomics and physiology of the genus Methanohalophilus, a prevalent methanogen in hydraulically fractured shale|journal=Environmental Microbiology|language=en|volume=20|issue=12|pages=4596–4611|doi=10.1111/1462-2920.14467|pmid=30394652|s2cid=53220420 |issn=1462-2912|doi-access=free|bibcode=2018EnvMi..20.4596B }}</ref> Genomic markers pointing at environmentally relevant factors are often non-exclusive. A survey of Methanogenic Thermoplasmata has found these organisms in human and animal intestinal tracts. This novel species was also found in other methanogenic environments such as wetland soils, though the group isolated in the wetlands did tend to have a larger number of genes encoding for anti-oxidation enzymes that were not present in the same group isolated in the human and animal intestinal tract.<ref>{{Cite journal|last1=Söllinger|first1=Andrea|last2=Schwab|first2=Clarissa|last3=Weinmaier|first3=Thomas|last4=Loy|first4=Alexander|last5=Tveit|first5=Alexander T.|last6=Schleper|first6=Christa|last7=Urich|first7=Tim|date=January 2016|editor-last=King|editor-first=Gary|title=Phylogenetic and genomic analysis of Methanomassiliicoccales in wetlands and animal intestinal tracts reveals clade-specific habitat preferences|journal=FEMS Microbiology Ecology|language=en|volume=92|issue=1|pages=fiv149|doi=10.1093/femsec/fiv149|pmid=26613748|issn=1574-6941|doi-access=free|hdl=10037/8522|hdl-access=free}}</ref> A common issue with identifying and discovering novel species of methanogens is that sometimes the genomic differences can be quite small, yet the research group decides they are different enough to separate into individual species. One study took a group of Methanocellales and ran a comparative genomic study. The three strains were originally considered identical, but a detailed approach to genomic isolation showed differences among their previously considered identical genomes. Differences were seen in gene copy number and there was also metabolic diversity associated with the genomic information.<ref>{{Cite journal|last1=Lyu|first1=Zhe|last2=Lu|first2=Yahai|date=June 2015|title=Comparative genomics of three M ethanocellales strains reveal novel taxonomic and metabolic features: Comparative genomics of three Methanocellales strains|journal=Environmental Microbiology Reports|language=en|volume=7|issue=3|pages=526–537|doi=10.1111/1758-2229.12283|pmid=25727385}}</ref>

Genomic signatures not only allow one to mark unique methanogens and genes relevant to environmental conditions; it has also led to a better understanding of the evolution of these archaea. Some methanogens must actively mitigate against oxic environments. Functional genes involved with the production of antioxidants have been found in methanogens, and some specific groups tend to have an enrichment of this genomic feature. Methanogens containing a genome with enriched antioxidant properties may provide evidence that this genomic addition may have occurred during the Great Oxygenation Event.<ref>{{Cite journal|last1=Lyu|first1=Zhe|last2=Lu|first2=Yahai|date=February 2018|title=Metabolic shift at the class level sheds light on adaptation of methanogens to oxidative environments|journal=The ISME Journal|language=en|volume=12|issue=2|pages=411–423|doi=10.1038/ismej.2017.173|issn=1751-7362|pmc=5776455|pmid=29135970|bibcode=2018ISMEJ..12..411L }}</ref> In another study, three strains from the lineage Thermoplasmatales isolated from animal gastro-intestinal tracts revealed evolutionary differences. The eukaryotic-like histone gene which is present in most methanogen genomes was not present, alluding to evidence that an ancestral branch was lost within Thermoplasmatales and related lineages.<ref>{{Cite journal|last1=Borrel|first1=Guillaume|last2=Parisot|first2=Nicolas|last3=Harris|first3=Hugh MB|last4=Peyretaillade|first4=Eric|last5=Gaci|first5=Nadia|last6=Tottey|first6=William|last7=Bardot|first7=Olivier|last8=Raymann|first8=Kasie|last9=Gribaldo|first9=Simonetta|last10=Peyret|first10=Pierre|last11=O'Toole|first11=Paul W|date=2014|title=Comparative genomics highlights the unique biology of Methanomassiliicoccales, a Thermoplasmatales-related seventh order of methanogenic archaea that encodes pyrrolysine|journal=BMC Genomics|language=en|volume=15|issue=1|pages=679|doi=10.1186/1471-2164-15-679|issn=1471-2164|pmc=4153887|pmid=25124552 |doi-access=free }}</ref> Furthermore, the group Methanomassiliicoccus has a genome which appears to have lost many common genes coding for the first several steps of methanogenesis. These genes appear to have been replaced by genes coding for a novel methylated methogenic pathway. This pathway has been reported in several types of environments, pointing to non-environment specific evolution, and may point to an ancestral deviation.<ref>{{Cite journal|last1=Borrel|first1=Guillaume|last2=O'Toole|first2=Paul W.|last3=Harris|first3=Hugh M.B.|last4=Peyret|first4=Pierre|last5=Brugère|first5=Jean-François|last6=Gribaldo|first6=Simonetta|date=October 2013|title=Phylogenomic Data Support a Seventh Order of Methylotrophic Methanogens and Provide Insights into the Evolution of Methanogenesis|journal=Genome Biology and Evolution|language=en|volume=5|issue=10|pages=1769–1780|doi=10.1093/gbe/evt128|issn=1759-6653|pmc=3814188|pmid=23985970}}</ref>