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Publications of the Week

Novel Classes and Evolutionary Turnover of Histone H2B Variants in the Mammalian Germline

By February 18, 2022No Comments

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This week we profile a recent publication in Molecular Biology and Evolution from Dr. Pravrutha Raman (pictured, center), Mary Callie Rominger (left), and Dr. Janet Young (right) the laboratory of Dr. Harmit Malik at Fred Hutch.

Can you provide a brief overview of your lab’s current research focus?

Our lab studies the causes and consequences of genetic conflicts that take place between different genomes (e.g., host-virus interactions) or between components of the same genome (e.g., chromosomal competition) from the perspective of both evolutionary biology and human disease. We use an evolutionary lens to discover adaptation by uncovering unexpected rapid evolution in genes involved in essential cellular processes such as chromosome segregation. For example, in previous work, we showed that unusual genetic conflicts during meiosis can drive the unexpectedly rapid evolution of centromeric DNA and proteins, which in turn may drive speciation.

What is the significance of the findings in this publication?

Our study discovered unexpected novelty and innovation during the evolution of essential DNA-packing proteins, called histones, in mammals. Although histones are typically highly conserved and slowly evolving, the H2B variants we discovered and characterized display high evolutionary turnover with gains and losses across species. Moreover, their evolutionary rate ranges from very conserved to rapidly evolving. These variants are enriched in mammalian testes and oocytes, the latter being an unusual expression site for histones. This study highlights the power of phylogenomic analyses to identify new proteins that have eluded us even within the human genome. It further reveals that still-unknown biological forces in the germline continually shape even repertoires of fundamental proteins.

What are the next steps for this research?

We plan to use human cells to decipher the molecular properties of these histones. Even though these histone variants are normally restricted to germline cells, they can be aberrantly turned on in cancer cells. We are interested in the causes and consequences of this aberrant expression on human cancers.

If you’d like us to mention your funding sources, please list them.

This work was supported by grants from the National Institutes of Health, from the Fondation pour la Recherche M├ędicale in France, and from the Howard Hughes Medical Institute.


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