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Open Access Highly Accessed Research article

Evolutionary history of histone demethylase families: distinct evolutionary patterns suggest functional divergence

Xiaofan Zhou12 and Hong Ma123*

Author Affiliations

1 The Intercollege Graduate Program in Cell and Developmental Biology, the Huck Institutes of the Life Sciences, the Pennsylvania State University, 415 Life Science Building, University Park, Pennsylvania 16802, USA

2 Department of Biology, the Institute of Molecular Evolutionary Genetics, the Pennsylvania State University, 405D Life Science Building, University Park, Pennsylvania 16802, USA

3 School of Life Sciences, the Institute of Plant Biology, the Center for Evolutionary Biology, the Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, PR China

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BMC Evolutionary Biology 2008, 8:294  doi:10.1186/1471-2148-8-294

Published: 24 October 2008



Histone methylation can dramatically affect chromatin structure and gene expression and was considered irreversible until recent discoveries of two families of histone demethylases, the KDM1 (previously LSD1) and JmjC domain-containing proteins. These two types of proteins have different functional domains and distinct substrate specificities. Although more and more KDM1 and JmjC proteins have been shown to have histone demethylase activity, our knowledge about their evolution history is limited.


We performed systematic phylogenetic analysis of these histone demethylase families and uncovered different evolutionary patterns. The KDM1 genes have been maintained with a stable low copy number in most organisms except for a few duplication events in flowering plants. In contrast, multiple genes for JmjC proteins with distinct domain architectures were present before the split of major eukaryotic groups, and experienced subsequent birth-and-death evolution. In addition, distinct evolutionary patterns can also be observed between animal and plant histone demethylases in both families. Furthermore, our results showed that some JmjC subfamilies contain only animal genes with specific demethylase activities, but do not have plant members.


Our study improves the understanding about the evolutionary history of KDM1 and JmjC genes and provides valuable insights into their functions. Based on the phylogenetic relationship, we discussed possible histone demethylase activities for several plant JmjC proteins. Finally, we proposed that the observed differences in evolutionary pattern imply functional divergence between animal and plant histone demethylases.