Líf - og heilbrigðisvísindaráðstefna Háskóla Íslands 2021

A region of ATG7 evolved in early vertebrates and might account for a new function

Main author: Valgerður Jakobína Hjaltalín
Institution or Company: University of Iceland

Co-Authors, Institution or Company:
Margrét Helga Ögmundsdóttir, University of Iceland. Arnar Pálsson, University of Iceland.

Introduction: Autophagy is a degradation process that is vital for cellular homeostasis. The process is required for clearance of detrimental cellular debris and the degraded building blocks can be re-used by the cell under nutrient deficiency. Studies on the essential autophagy protein ATG7 have shown that ATG7 is also involved in  autophagy independent functions. These studies have exclusively been done in mammalian cells or mice and therefore it has not been explored whether this protein plays an additional role in other species. Complete knockout of ATG7 is neonatal lethal in mice, but fruit flies are viable. This indicates a more important role of ATG7 in mice and evokes the question whether ATG7 has gained a new function in mammals or vertebrates.

Materials and methods: We performed an evolutionary analysis of ATG7 to explore whether new regions of the protein have evolved in mammals. We compared the intensity and direction of natural selection across vertebrates using computational models.

Results: We have described a region of ATG7 that evolved in early vertebrates. Interestingly, two cancer related sites reside in this region. Further analysis revealed that the region is generally under stronger negative selection in mammals than other vertebrates, apart from one of the cancer related sites which was under significant positive selection.

Conclusions: These results show that a new region of ATG7 evolved in early vertebrates and has stabilized in mammals, being overall under strong purifying selection. This suggests that this region might account for a new function of the protein.


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