Herasome

Herasome is a term coined by Eroglu and Zocher (2024) to describe heritable amyloid-like aggregates with developmental influence, arising from the observation of noncanonical inheritance of phenotypic information through protein amyloids. As they state, "...given the physiological presence of heritable amyloid-like aggregates and their developmental influence, we propose to term them ‘herasomes’ (Eroglu et al., 2024)."

Noncanonical inheritance of phenotypic information by protein amyloids (Eroglu et al., 2024)

In the nematode Caenorhabditis elegans, the determination of germ cell sex is not solely dictated by genetics but is also influenced by epigenetic factors. Typically, hermaphrodites produce sperm first and then switch to oocytes, enabling self-fertilization, while males only produce sperm. However, when genes F22D6.2 and F56F3.4 are mutated, a curious phenomenon occurs: subsequent generations of worms show a gradual decline in their ability to self-fertilize, eventually leading to sterility at a higher temperature (25°C). This sterility can be reversed by returning the worms to a lower temperature (20°C) for several generations, highlighting an environmental influence on reproductive capacity across generations.

Evidence suggests that this multigenerational effect might be mediated by the inheritance of protein aggregates called amyloids. Parental amyloid structures and the proteins associated with them can be found in the germ cells of their offspring, existing alongside newly formed amyloids. This suggests that a small number of these self-replicating amyloid aggregates are passed down, acting as "seeds" for further amyloid growth in the next generation. These inherited amyloids appear to influence the protein degradation machinery (proteasomes) in offspring, potentially altering the levels of specific proteins across generations based on the type and quantity of inherited amyloid. The fact that proteasome components associate with these amyloids supports this idea. Furthermore, the source of the parental amyloids can lead to different outcomes in the offspring, possibly due to variations in amyloid structure that affect proteasome function differently. While the precise nature of these amyloids and their interaction with the proteasome still requires investigation, the direct inheritance of amyloid-associated proteins demonstrates a non-traditional way in which information, beyond just DNA sequence, can be passed down and influence development.

The genetic and protein studies show that the 26S proteasome and its associated regulatory components play a crucial role in maintaining heritable amyloid structures across generations. These inherited amyloids, in turn, are essential for the correct differentiation of germ cells according to their sex. Based on these findings, the study suggests that the inheritance of a protein-based epigenetic memory allows organisms to synchronize developmental timing and patterns with environmental cues, potentially enhancing their ability to adapt and survive.

References

Eroglu, M., Zocher, T., McAuley, J., Webster, R., Xiao, M. Z. X., Yu, B., Mok, C., & Derry, W. B. (2024). Noncanonical inheritance of phenotypic information by protein amyloids. eLife, 13, e87331.

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