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Figure 3. The evolutionary fate (i.e. how the ancestral function is carried out by the paralog pair ― 272 ―the other paralog to evolve under less constraint, while the ULK (ULK1 and ULK2), GABARAP (GABARAP and GABARAPL1) and LC3 pairs are more consistent with hypofunctionalization or subfunctionalization (i.e. ancestral function is shared between paralogs). We also found evidence of positive selection in the paralogs that evolved under less constraint in some cases, indicative of evolutionary adaptation and possibly the acquirement of new functions. post-duplication) of each paralog pair was classified based on whether one individual paralog or the total expression of two paralogs has the expression closest to the pre-duplication level.The ATG genes can have both autophagic and non-autophagic functions1). Because the autophagy pathway is an ancient pathway broadly conserved in eukaryotes, the ancestral function (or one of the ancestral functions) of the ATG genes is likely the autophagic function. Following this line of thought, it is expected that in pairs where one paralog likely preserves the ancestral function, this paralog would be most important for autophagy while the other paralog may be dispensable, whereas in pairs classified as hypofunctionalization or subfunctionalization, both paralogs would be important for autophagy. Indeed, our expectation based on the evolutionary fate categories is mostly consistent with existing studies comparing the function of ATG paralogs (in mammalian cells).PerspectivesGene duplication, prevalent in all three domains of life, is a major driver of evolution. Our study reveals the post-duplication evolutionary dynamics of the ATG genes in vertebrates and provides a time axis for the interpretation of functional differences between paralogs.

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