WDR75: An essential protein for ribosome assembly undergoing purifying selection

Area of Science:

• Molecular Biology
• Evolutionary Biology
• Structural Biology

Background:

• Ribosomes are essential for protein synthesis, with the small subunit (SSU) critical for translation initiation.
• The SSU processome is a large complex involved in ribosome biogenesis.
• WDR75 is a key protein within the SSU processome, binding rRNA to facilitate SSU formation.

Purpose of the Study:

• To investigate the molecular evolution, 3D structure, and phylogeny of mammalian WDR75.
• To understand the evolutionary pressures acting on WDR75, given its crucial role in ribosome assembly.

Main Methods:

• Comparative sequence analysis of 70 mammalian WDR75 sequences.
• Identification of sites under selection (purifying and positive).
• Phylogenetic analysis to reconstruct evolutionary relationships.

Main Results:

• Approximately 25% of WDR75 sites showed significant purifying selection, with stronger selection in beta-sheet structures compared to coils.
• Phylogenetic analysis confirmed mammalian relationships but revealed an accelerated evolutionary rate in mouse-eared bats.
• Diversifying selection was detected specifically among African great apes, with no evidence of purifying selection on individual branches.

Conclusions:

• WDR75 is under significant evolutionary constraint, supporting its essential role in SSU assembly.
• Specific evolutionary patterns, including accelerated evolution in bats and diversifying selection in apes, highlight unique evolutionary trajectories.
• Structural and evolutionary insights into WDR75 can inform our understanding of ribosome biogenesis and evolution.