biostudies-literatureLi ZShenzhen Medical Research FundNational Natural Science Foundation of ChinaSouthern Marine Science and Engineering Guangdong Laboratory (Guangzhou)Southern Marine Science and Engineering Guangdong LaboratoryShenzhen University 2035 Program for Excellent Researchmsaf330https://www.ebi.ac.uk/biostudies/studies/S-EPMC12770985biostudies-literatureUnknown43(1)Eukarya resemble Archaea in DNA replication. Analysis of the DNA replication machinery of Asgard archaea may provide a valuable test of the hypothesis that this phylum is the origin of Eukarya. Among the replication proteins, primase, which comprises the catalytic subunit PriS and the non-catalytic subunit PriL, synthesizes primers for extension by DNA polymerase. Here, we show that Asgard primases fall into two major groups, denoted the Heimdall group and the Loki group, which are phylogenetically and structurally more closely related to eukaryotic primases and to primases from non-Asgard archaea, respectively. Notably, like human PriL, PriL of the Heimdall group possesses an extra C-terminal domain, which, absent in archaeal PriL of the non-Heimdall group, presumably serves to enhance thMolecular biology and evolutionPhylogenetic and functional characterization of Asgard primases.PMC1277098532393970B2301005GML202400022022B002Liu YLi ZHuang LLi MfalsePhylogenetic and functional characterization of Asgard primases.Eukarya resemble Archaea in DNA replication. Analysis of the DNA replication machinery of Asgard archaea may provide a valuable test of the hypothesis that this phylum is the origin of Eukarya. Among the replication proteins, primase, which comprises the catalytic subunit PriS and the non-catalytic subunit PriL, synthesizes primers for extension by DNA polymerase. Here, we show that Asgard primases fall into two major groups, denoted the Heimdall group and the Loki group, which are phylogenetically and structurally more closely related to eukaryotic primases and to primases from non-Asgard archaea, respectively. Notably, like human PriL, PriL of the Heimdall group possesses an extra C-terminal domain, which, absent in archaeal PriL of the non-Heimdall group, presumably serves to enhance th2026-01-01T00:00:00Z2026 Jan2026-07-15T13:57:39.129Z2026-07-05T03:12:25.289ZS-EPMC127709854143604210.1093/molbev/msaf330