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Synopsis Basic science research, also called “curiosity-driven research,” is fundamental work done with no immediate economic goals but rather a focus on discovery for discovery’s sake. However, basic science research is often needed to seed more applied, economically oriented, research. Both basic and applied research efforts are important aspects of the “bioeconomy,” defined here as the contributions to the overall economy from various biology-related fields spanning everything from museum-based natural history research to agricultural food and material production to healthcare. Here, we propose that more collaborative efforts across federal granting agencies in a venture-capitalist-like “PO-driven model” can help drive applied innovation from collaborations facilitated by program officers (POs). POs from NSF, DOE, DARPA, USDA, NASA, and other federal agencies should seek out parallel and complementary research ideas from grantees and provide funds to build teams of researchers who may otherwise be unaware of one another. Researchers working in different fields may also be unaware that the different organisms they are studying independently may have evolved similar traits (i.e., convergent evolution) that POs may recognize and who can then facilitate novel research avenues connecting those independent researchers (we provide examples of some projects inspired by convergent evolution here). In this top-down approach to research funding, the US bioeconomy will be pouring fuel on the fire of scientific productivity in this country. 

Abstract DNA repair proteins can be recruited by their histone reader domains to specific epigenomic features, with consequences on intragenomic mutation rate variation. Here, we investigated H3K4me1-associated hypomutation in plants. We first examined 2 proteins which, in plants, contain Tudor histone reader domains: PRECOCIOUS DISSOCIATION OF SISTERS 5 (PDS5C), involved in homology-directed repair, and MUTS HOMOLOG 6 (MSH6), a mismatch repair protein. The MSH6 Tudor domain of Arabidopsis (Arabidopsis thaliana) binds to H3K4me1 as previously demonstrated for PDS5C, which localizes to H3K4me1-rich gene bodies and essential genes. Mutations revealed by ultradeep sequencing of wild-type and msh6 knockout lines in Arabidopsis show that functional MSH6 is critical for the reduced rate of single-base substitution (SBS) mutations in gene bodies and H3K4me1-rich regions. We explored the breadth of these mechanisms among plants by examining a large rice (Oryza sativa) mutation data set. H3K4me1-associated hypomutation is conserved in rice as are the H3K4me1-binding residues of MSH6 and PDS5C Tudor domains. Recruitment of DNA repair proteins by H3K4me1 in plants reveals convergent, but distinct, epigenome-recruited DNA repair mechanisms from those well described in humans. The emergent model of H3K4me1-recruited repair in plants is consistent with evolutionary theory regarding mutation modifier systems and offers mechanistic insight into intragenomic mutation rate variation in plants. 

Summary Processes affecting rates of sequence polymorphism are fundamental to the evolution of gene duplicates. The relationship between gene activity and sequence polymorphism can influence the likelihood that functionally redundant gene copies are co‐maintained in stable evolutionary equilibria vs other outcomes such as neofunctionalization.Here, we investigate genic variation in epigenome‐associated polymorphism rates inArabidopsis thalianaand consider whether these affect the evolution of gene duplicates. We compared the frequency of sequence polymorphism and patterns of genetic differentiation between genes classified by exon methylation patterns: unmethylated (unM), gene‐body methylated (gbM), and transposon‐like methylated (teM) states, which reflect divergence in gene expression.We found that the frequency of polymorphism was higher in teM (transcriptionally repressed, tissue‐specific) genes and lower in gbM (active, constitutively expressed) genes. Comparisons of gene duplicates were largely consistent with genome‐wide patterns – gene copies that exhibit teM accumulate more variation, evolve faster, and are in chromatin states associated with reduced DNA repair.This relationship between expression, the epigenome, and polymorphism may lead to the breakdown of equilibrium states that would otherwise maintain genetic redundancies. Epigenome‐mediated polymorphism rate variation may facilitate the evolution of novel gene functions in duplicate paralogs maintained over evolutionary time.