[
International Worm Meeting,
2019]
The "Fluctuation-Dissipation Relation" of statistical physics shows that the random fluctuation ("noise") experienced by certain kinds of physical systems at thermodynamic equilibrium is expected to be proportional to the response of the system to perturbation. Biological organisms are a special kind of physical system, and it has been posited that the Fluctuation-Dissipation Relation applies to many aspects of biological systems. Specifically, it has been suggested that the phenotypic variance exhibited among a genetically uniform set of individuals raised in a uniform environment (= "noise") should be proportional to the consistent variation in phenotype between sets of genetically identical individuals raised in different environments (= "phenotypic plasticity"). That is, the FDR applied to biological systems predicts that phenotypic noise within a uniform environment should be proportional to phenotypic plasticity between environments. If so, it implies a fundamental tradeoff in fitness components, such that genotypes that are more capable of responding to systematic environmental variation - which is adaptive, all else equal - will experience more random phenotypic variation even in the optimal environment - which is maladaptive, all else equal. If indeed there is a fundamental tradeoff between noise and plasticity, at an evolutionary optimum, there are three possible outcomes: (1) natural selection may favor greater plasticity at the cost of additional noise; (2) robustness ("quiet") may be favored at the cost of restricted plasticity, or (3, and least likely), both plasticity and robustness may be optimal. Under this scenario, the cumulative effects of deleterious mutations will cause the system to evolve away from the selective optimum, thereby illuminating the pattern of natural selection. Alternatively, if the relationship between noise and plasticity is an emergent property of the system, or if there is no relationship, the relationship will remain unchanged, or will change at random. To test these competing hypotheses, we assayed fitness, and 15 other fitness-proximal traits, in four environments, in ~130 mutation accumulation (MA) lines of C. elegans, generated from two starting ancestors, N2 and PB306. We observe that both noise and plasticity in relative fitness increase with mutation accumulation. In addition, the mutational variance (VM) of noise is on the same order of magnitude as VM for trait means. However, we did not find covariance between noise and plasticity, which suggests a role for natural selection in shaping this relationship in the wild. In addition, we find that mutational heritability of mean trait value and noise in trait value are highly correlated across the 16 traits we measured.
[
International Worm Meeting,
2021]
A crucial process in life is the ability of cells to pass on information to their descendants. This transmission can occur at several levels from genetics to epigenetics. Epigenetic inheritance refers to the heritable phenotypes affected by gene expression without altering the DNA sequence and occurs through various factors including histone modifications. Interruption of this transmission process can lead to severe developmental defects and fertility diseases. Methylation of histone H3 at position 27 (H3K27me3) is an epigenetic mark that is associated with heterochromatin and repressed gene expression. Several studies have demonstrated that the genomic patterns of H3K27me3 can be inherited from one generation to the next by depositing H3K27me3 histones and PRC21. However, the limits of this inheritance are difficult to test because PRC2 mutants are maternal-effect sterile in C. elegans. We have recently shown that the expression of an H3.3K27M mutant acts in a dominant-negative manner and alters genomic H3K27me3 patterns and distribution of PRC2 and results in infertility phenotypes in C. elegans2. We used this strain to follow the trans-generational inheritance of the H3.3K27M-induced phenotypes. Strikingly, we observed that the altered patterning of H3K27me3 and the fertility defects are heritable for multiple generations after the H3.3K27M mutation is lost. These findings were also validated in a tetracycline-inducible system where we can abruptly switch on and off the H3.3K27M expression. We performed a targeted RNAi screen in our tetracycline-inducible system and detected several enhancer and suppressor modifiers of H3.3K27M defects such as chromatin remodeling complexes, the nuclear RNAi pathway, and histone writer and reader complexes. Overall, our results revealed that the transmission of H3K27me3 is an epigenetically programmed event that can last for generations and that several biological pathways seem to be involved in the regulation of transmission of H3K27me3 patterns across generations. 1. L. J. Gaydos, W. Wang, S. Strome. H3K27me and PRC2 transmit a memory of repression across generations and during development. Science 345, 1515-1518 American Association for the Advancement of Science (AAAS), 2014. 2. Kamila Delaney, Maude Strobino, Joanna M. Wenda, Andrzej Pankowski, Florian A. Steiner. H3.3K27M-induced chromatin changes drive ectopic replication through misregulation of the JNK pathway in C. elegans. Nature Communications 10 Springer Science and Business Media LLC, 2019.