%0 Journal Article %A Yichun Qiu %A Zhen Li %A Dirk Walther %A Claudia Köhler %T Updated phylogeny and protein structure predictions revise the hypothesis on the origin of MADS-box transcription factors in land plants %D 2023 %R 10.1101/2023.01.10.523452 %J bioRxiv %P 2023.01.10.523452 %X MADS-box transcription factors (TFs) are broadly present in eukaryotic genomes. Varying by domain structures, MADS-box TFs in plants are categorized into M-type and MIKC-type. For about twenty years, M-type genes were considered closely related to the SRF genes in animals, collectively referred to as Type I MADS-box genes. MIKC-type and animal MEF2 genes were grouped as Type II, presumably duplicated with Type I genes before the divergence of eukaryotes. Exploiting available genomic data, we reassessed the evolutionary history of eukaryotic MADS-box genes and propose an alternative hypothesis. Our phylogenetic analyses support the ancient duplication of SRF/MEF2; however, both M-type and MIKC-type originated from the lineage of MEF2 via another duplication event before the divergence of land plants. Protein structures predicted by AlphaFold2 support this evolutionary scenario, with both M-type and MIKC-type proteins in plants resembling the MEF2 3D structure, distinct from SRF. Therefore, we propose that the most recent common ancestor of Archaeplastida (the kingdom Plantae) likely did not inherit any SRF gene. The retained MEF2 TFs acquired a Keratin-like domain and became MIKC-type upon the evolution of Streptophyta. Subsequently in land plants, M-type TFs evolved from a duplicated MIKC-type precursor through loss of the Keratin-like domain. M-type and MIKC-type then largely expanded and functionally differentiated in concert with the increasing complexity of land plant body architecture. We attribute the adaption to the terrestrial environment partly to the divergence among MEF2-type MADS-box genes and the repetitive recruitment of these originally stress-responsive TFs into developmental programs, especially those underlying reproduction.Competing Interest StatementThe authors have declared no competing interest. %U https://www.biorxiv.org/content/biorxiv/early/2023/01/11/2023.01.10.523452.full.pdf