加拿大多伦多大学W. Brent Derry等研究人员合作揭示蛋白质淀粉样体的非经典表型信息遗传。相关论文于2024年9月2日在线发表在《自然—细胞生物学》杂志上。

研究人员识别出在野生型动物中稳定遗传的类似淀粉样体的蛋白质结构，并影响表型。通过遗传、环境或药物处理扰动这些结构会导致发育表型，这些表型可以通过表观遗传学传递给后代。从不同表型背景中分离出的淀粉样体注射到新的动物体内，可以在后代中重现相关的表型。

遗传学和蛋白质组学分析揭示了26S蛋白酶体及其保守的调节因子在代际间维持可遗传的淀粉样体，这使得适当的生殖细胞性别分化成为可能。研究人员提出，蛋白质表观遗传记忆的遗传协调了发育时序和模式与环境，以赋予适应性。

据了解，已知的动物可遗传表型信息都是通过直接遗传核酸、其共价修饰或调节相关基因组区域表达的组蛋白修饰来传递的。然而，许多家族性特征和疾病无法归因于已知的可遗传分子因素。

附：英文原文

Title: Noncanonical inheritance of phenotypic information by protein amyloids

Author: Eroglu, Matthew, Zocher, Tanner, McAuley, Jacob, Webster, Rachel, Xiao, Maggie Z. X., Yu, Bin, Mok, Calvin, Derry, W. Brent

Issue&Volume: 2024-09-02

Abstract: All known heritable phenotypic information in animals is transmitted by direct inheritance of nucleic acids, their covalent modifications or histone modifications that modulate expression of associated genomic regions. Nonetheless, numerous familial traits and disorders cannot be attributed to known heritable molecular factors. Here we identify amyloid-like protein structures that are stably inherited in wild-type animals and influence traits. Their perturbation by genetic, environmental or pharmacological treatments leads to developmental phenotypes that can be epigenetically passed onto progeny. Injection of amyloids isolated from different phenotypic backgrounds into naive animals recapitulates the associated phenotype in offspring. Genetic and proteomic analyses reveal that the 26S proteasome and its conserved regulators maintain heritable amyloids across generations, which enables proper germ cell sex differentiation. We propose that inheritance of a proteinaceous epigenetic memory coordinates developmental timing and patterning with the environment to confer adaptive fitness.

DOI: 10.1038/s41556-024-01494-9

Source: https://www.nature.com/articles/s41556-024-01494-9