Postdoc - Biomedicine

The evolution of self-consumption

January 16, 2022

Photo by Kelly Sikkema

To study the evolution of a body part or a trait, one needs to address two questions. First, what is the trait for? Second, how could it evolve by small steps that gave some advantage to the organism that carried them? It is also necessary to suggest a plausible mechanism by which this progression could proceed. The natural place to start is to analyze the function of the trait in present-day organisms and trace it back in time to see how the organism got there. At the molecular level, one starts with a protein sequence, finds its relatives in related organisms, and examines its potential ancestral function. This historical approach is often nuanced by cases where the part has been lost in descendants of the ancestor or the emergence of similar traits in unrelated organisms.

The ancestral function of autophagy

Autophagy is a complex process involving engulfing cellular materials destined for degradation. The process starts by tagging the targets using specialized proteins; This could be more or less specific depending on the particular subtype of autophagy. Earlier degradation system probably involved marking part of the protein sequence using another, which signifies the removal of this protein in a specialized structure. Prokaryotes use an analogous method to remove proteins. Hughes and Rusten (2007) used this functional analysis to suggest an ancestral form of autophagy in prokaryotes, but the process as we know it is probably exclusive to the eukaryotic lineages. Autophagy also requires a membrane around its target and forming a vascular structure that fuses with another containing the lytic enzymes. The membrane requirement immediately places the emergence of autophagy at a time when membranes had already evolved.

However, the question of what a system is for can be answered at different levels. In the case of the degradation of cellular materials, one can always ask, what is this for? The likely explanation is for resisting starvation and infection. Under starvation conditions, cells recycle materials to produce energy and components to build necessary structures. Recycling gives a clear advantage to organisms that evolved autophagy since they can survive stressful conditions such as the lack of nutrients. Targeting and removing bacterial infections can similarly be advantageous.

Comparative analysis of autophagy-related genes in tens of species spanning the kingdoms of life suggested another possibility on the original driving force behind the evolution of autophagy. Yang and colleagues (2017) observed that the core autophagy proteins are widely distributed among species but not those involved in selective autophagy. More importantly, this distribution was most similar to mitochondrial importing proteins. Given the known function of autophagy in removing damaged mitochondria, it could be that autophagy originated as a quality control system for mitochondria.

Autophagy is prevalent in eukaryotes today and can be traced to their last common ancestor. Nevertheless, a few eukaryotes do not have it. They represent a case where a function had evolved and was lost. It is unlikely that all these organisms evolved the autophagy machinery independently.

The evolution of autophagy machinery

Gene duplication is a crucial mechanism by which evolution generates novelty. A gene is duplicated, and the new copy diverges in sequence and function. Several autophagy-related genes exist today. A recent review article by Zhang and colleagues (2021) traced the origin and function of many of these genes. Some participate in forming the targeting, engulfing, and degrading the cellular materials. Others, although related, were coopted to unrelated functions.

The existence of two or more proteins of similar structure and function suggests redundancy. Careful analysis of these cases cannot always dismiss this possibility but could also offer others. For example, similar proteins could work in different tissue or perform additional tasks.

In short, through gene duplication, sophisticated autophagy machinery evolved as a system for recycling cellular materials; this gave an advantage to eukaryotes as they could survive harsh conditions, maintain energy production, and/or fend off infections. The similarity of autophagy to other degradation systems and the requirement of membranes places its evolution around the time where membrane structures and tagging systems had evolved. Both are abilities shared by most descendants of the last common eukaryotic ancestors.


  1. Hughes T, Rusten TE. Origin and evolution of self-consumption: autophagy. Adv Exp Med Biol. 2007;607:111-8.
  2. Zhang S, Hama Y, Mizushima N. The evolution of autophagy proteins - diversification in eukaryotes and potential ancestors in prokaryotes. J Cell Sci. 2021 Jul 1;134(13):jcs233742.
  3. Yang, J., Chai, X. Q., Zhao, X. X., & Li, X. (2017). Comparative genomics revealed the origin and evolution of autophagy pathway. Journal of Systematics and Evolution, 55(1), 71–82.