Interview with the authors: Museum epigenomics: Characterizing cytosine methylation in historic museum specimens

Recent work has shown that it may be possible to characterize epigenetic markers from museum specimens, suggesting yet another potential contribution of collections-based research. In their recent Molecular Ecology Resources paper, Rubi et al. used ddRAD and bisulphite treatment to characterize cytosine methylation in deer mice (Peromyscus spp.). They characterized methylation in specimens from 1940, 2003, and 2013-2016. While they were able to characterize patterns in all specimens, older specimens had reduced methylation estimates, less data, and more interindividual variation in data yield than did new specimens. Rubi et al. demonstrate the promise of museum epigenetics while highlighting technical challenges that researchers should consider. Read the interview with lead author Dr. Tricia Rubi below to get a behind-the-scenes look at the research behind the paper.

Read the full paper here.

Peromyscus maniculatus skull collected in 2002 and housed in the University of Michigan Museum of Zoology collection. Photo Credit: Dr. Tricia Rubi

What led to your interest in this topic / what was the motivation for this study? 

When I wrote the original proposal for this work, the earliest papers had just been published in the field of ancient epigenomics (epigenetic studies using paleontological or archaeological specimens). My proposal centered around museum specimens, and I realized that no work had been done looking at epigenetic effects in more recent historic specimens (decades to centuries old), which comprise the bulk of museum collections. The recent field of museum genomics has already opened up a range of new directions for research using collections; I believe that museum epigenomics could be a similar frontier in collections-based research. In particular, epigenomic studies using museum collections could allow us to characterize change over time, which may help clarify the role of epigenetic effects in ecological and evolutionary processes.

What difficulties did you run into along the way? 

As is the case when developing any novel protocol, we encountered a variety of challenges and dead ends. However, we found that the main challenge for DNA methylation work using museum specimens was actually the same as the main challenge for regular genetic work using museum specimens: recovering usable amounts of DNA in the initial DNA extraction. DNA quantity and quality seemed to be a better predictor of success than specimen age; our oldest specimens (~76 years old) with higher DNA concentrations yielded a similar amount of methylation data relative to much “younger” specimens. The upside is that this challenge is already a familiar one to researchers conducting museum genomics work. Our data suggests that historic DNA samples that have been successfully used for genomic analyses are probably also well suited for methylation analyses.

What is the biggest or most surprising innovation highlighted in this study? 

I think the main takeaway from this study is that DNA methylation analyses using historic collections is feasible, even for lower quality specimens such as traditional bone preparations that are several decades old. Our oldest specimens in this study were dried skulls collected in 1940; while those specimens showed considerable variation in the amount of recoverable DNA, the specimens that yielded higher DNA concentrations performed well in our analyses.

Moving forward, what are the next steps in this area of research?

There is plenty of work to be done! In this paper we highlight future directions for both developing methodology and applying museum epigenomics to ecological and evolutionary questions. Increasing the number of sequenced methylation markers or refining protocols for targeted sequencing are some obvious first steps in improving methods. Museum epigenomics approaches could be used to tackle a variety of questions in ecological and evolutionary epigenomics. In particular, epigenomic studies using museum specimens could be used to infer gene expression in past populations, or to directly measure how epigenetic markers change over time. 

What would your message be for students about to start developing or using novel techniques in Molecular Ecology? 

Developing or refining novel techniques is an important and potentially rewarding process, but it requires enormous patience, as well as correctly managed expectations about the outcomes of the work. Researchers should be prepared for slower progress and a higher failure rate. Even when protocols do work, it may be more difficult to test broader ecological hypotheses due to unforeseen problems or non-optimal results. However, the upside is that projects using novel approaches can provide an important contribution to the field regardless of the specific outcomes of the work. My advice would be to design projects with several contingency plans to ensure that publishable data can be produced, and to factor in extra time for troubleshooting each step of the novel protocols.

Describe the significance of this research for the general scientific community in one sentence.

Natural history specimens retain patterns of in vivo DNA methylation, the best studied epigenetic marker; museum epigenomics may be the next frontier in collections-based research.

References

Rubi TL, Knowles LL, Dantzer B. Museum epigenomics: Characterizing cytosine methylation in historic museum specimens. Mol Ecol Resour. 2020;20:1161–1170.

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