Reframing Formalin: A Molecular Opportunity Enabling Historical Epigenomics and Retrospective Gene Expression Studies

Area of Science:

• Molecular biology
• Genomics
• Paleontology

Background:

• Formalin fixation of museum specimens historically hindered molecular research due to DNA damage.
• Advancements in DNA extraction and sequencing methods are overcoming these fixation challenges.
• Formalin fixation uniquely preserves in situ DNA-protein interactions, offering a snapshot of gene expression.

Purpose of the Study:

• To review the historical use of formaldehyde in collections.
• To discuss how molecular techniques can surmount fixation challenges.
• To highlight the potential of analyzing preserved specimens for historical gene expression and regulatory insights.

Main Methods:

• Hot alkaline lysis and proteinase K digestion for DNA extraction.
• Genome-wide re-sequencing and targeted locus-specific sequencing.
• Chromatin profiling assays such as MNase-seq and FAIRE-seq.

Main Results:

• Formalin-fixed specimens can be used for advanced molecular analyses, including genome sequencing.
• Formalin fixation preserves DNA-protein interactions, revealing insights into chromatin accessibility and gene regulation.
• Molecular profiling of fluid-preserved specimens enables tissue-specific gene expression analysis across a broader range of historical samples.

Conclusions:

• Formalin fixation is no longer an insurmountable barrier to molecular research in museum collections.
• Analysis of preserved specimens provides invaluable insights into historical genomes and gene expression profiles.
• Integrating molecular genetics with museum collections aids in understanding past biological events and predicting future environmental impacts.