Fungi: Gene Activator Role Discovered
High levels of DNA base modification reported in early-derived fungi.
DNA, the molecule carrying instructions for development, growth, function, and reproduction, is made up of four bases: cytosine (C), guanine (G), adenine (A), and thymine (T)–defining the genetic code. When the organism’s genetic code is modified by changing a single base this can cause changes in protein structure and function, impacting an organism’s traits. However, there are other subtler changes which can affect the activity of a DNA segment without changing the sequence. One of the most common examples involves the methylation (addition of a methyl group) of cytosine (C) on the 5th position of its carbon ring (5mC). This research explores one of the other less known modifications, adding a methyl group to base 6 of adenine (6mA) in early-diverging fungi.
In comparison to other lineages, early-diverging fungi have not been well studied or understood. However, many of these fungi are powerful plant biomass degraders with potential bioenergy applications. In this study, the discovery of adenine methylation associated with effects on gene expression in early-diverging fungi may explain the historic difficulty in altering the DNA of these early-diverging fungi, and aid in the development of future tools for their genetic modification.
The Fungi kingdom is estimated to be ~1 billion years old; the first six phyla comprise the ‘early-diverging’ fungi and the last two phyla make-up the Dikarya, which evolved ~500 million years ago. In this study, for the first time, 6mA base modification was identified as a widespread marker for transcriptionally active genes in early diverging fungi. The researchers examined long-read sequences from 16 diverse fungal genomes for the presence of adenine methylation. In the early-diverging fungi up to 2.8% of adenines were methylated, much higher than is seen in comparison to the eukaryotes and the more derived fungi (both less than 0.4%). Interestingly, despite fungi and animals’ closer phylogenetic relation, early-deriving fungi and algae-two distantly related kingdoms-are more similar in 6mA profiles than their more recently derived- (but more closely related)- fungi and animals. In early-derived fungi and algae, 6mA’s presence signals gene expression, while the role appears reversed in animals. This significant finding suggests 6mA’s association with gene expression is ancestral to the eukaryotic domain of life. This research also represents a previously uncharacterized difference between the role of 6mA in early-derived fungi and Dikarya of gene suppression and expression. More broadly this research highlights the variation in how 6mA is used to modify gene expression across eukaryotes, further defining the collective understanding of transcriptional regulation in this domain of life.
Igor V Grigoriev
DOE Joint Genome Institute
Work conducted by the US Department of Energy Joint Genome Institute, a DOE Office of Science User Facility, is supported by the Office of Science of the US Department of Energy under Contract No. DE-AC02-05CH11231. This work was partially supported by funding from the National Science Foundation (DEB-1441715 to JES, DEB-1441604 to J.W.S. and DEB-1354625 to T.Y.J. and I.V.G.). This work was further supported by the Office of Science (BER), US Department of Energy (DE-SC0010352) and the Institute for Collaborative Biotechnologies through grant W911NF-09- 0001. R.J.S. is supported by funding from the Office of the Vice President of Research at UGA as well as the Pew Charitable Trusts.
S.J. Mondo, R.O. Dannebaum, R.C. Kuo, K.B. Louie, A.J. Bewick, K. LaButti, S. Haridas, A. Kuo, A. Salamov, S.R. Ahrendt, R. Lau, B.P. Powen, A. Lipzen, W. Sullivan, B.B. Andreopoulos, A. Clum, E. Lindquist, C. Daum, J. Magnuson, T.Y. James, M.A. O’Malley, J.E. Stajich, J.W. Spatafora, A. Visel, I.V. Grigoriev, “Widespread adenine N6-methylation of active genes in fungi” Nature Genetics (2017). [DOI: 10.1038/ng.3859].