Ancient complement and lineage-specific evolution of the Sec7 ARF GEF proteins in eukaryotes

Area of Science:

• Evolutionary biology
• Cellular and molecular biology
• Genomics

Background:

• Guanine nucleotide exchange factors (GEFs) initiate signaling for regulatory GTPases, controlling essential cellular processes.
• ADP-ribosylation factor (ARF) GTPases regulate bidirectional membrane trafficking, with their complexity evolving alongside eukaryotic systems.
• Diverse families of GEFs typically activate distinct GTPase families.

Purpose of the Study:

• To perform phylogenetic analyses of ADP-ribosylation factor (ARF) Guanine nucleotide exchange factors (GEFs) across eukaryotes.
• To understand the evolutionary origins and diversification of ARF GEFs.
• To generate hypotheses about ARF GEF functions and their role in eukaryotic cellular complexity.

Main Methods:

• Phylogenetic analyses of ARF GEFs, identified by the presence of the Sec7 domain, were conducted in eukaryotes.
• Comparative evolutionary analysis of ARF GTPases and their GTPase-activating proteins was performed.

Main Results:

• Three ARF GEF subfamilies (BIG, GBF1, cytohesins) were present in the common ancestor of all eukaryotes.
• Four additional subfamilies (EFA6/PSD, IQSEC7/BRAG, FBX8, TBS) evolved later and are specific to certain eukaryotic clades, all derived from cytohesins.
• A novel cytohesin-derived subfamily (ankyrin repeat-containing cytohesin) independently evolved in amoebozoans and SAR/haptophyte clades.

Conclusions:

• The study elucidates the deep evolutionary history of ARF GEFs, revealing ancient origins and subsequent diversification.
• The findings provide insights into the co-evolution of ARF GTPases and their regulators, contributing to eukaryotic cellular complexity.
• Understanding ARF GEF evolution aids in hypothesizing protein functions and the development of cellular trafficking systems.