Neofunctionalization of ciliary BBS proteins to nuclear roles is likely a frequent innovation across eukaryotes

Alexander Ewerling; Vanessa Maissl; Bill Wickstead; Helen Louise May-Simera

doi:10.1016/j.isci.2023.106410

Neofunctionalization of ciliary BBS proteins to nuclear roles is likely a frequent innovation across eukaryotes

iScience. 2023 Mar 16;26(4):106410. doi: 10.1016/j.isci.2023.106410. eCollection 2023 Apr 21.

Authors

Alexander Ewerling¹, Vanessa Maissl¹, Bill Wickstead², Helen Louise May-Simera¹

Affiliations

¹ Institute of Molecular Physiology, Faculty of Biology, Johannes Gutenberg-University Mainz, Mainz, Germany.
² School of Life Sciences, University of Nottingham, Nottingham, UK.

Abstract

The eukaryotic BBSome is a transport complex within cilia and assembled by chaperonin-like BBS proteins. Recent work indicates nuclear functions for BBS proteins in mammals, but it is unclear how common these are in extant proteins or when they evolved. We screened for BBS orthologues across a diverse set of eukaryotes, consolidated nuclear association via signal sequence predictions and permutation analysis, and validated nuclear localization in mammalian cells via fractionation and immunocytochemistry. BBS proteins are-with exceptions-conserved as a set in ciliated species. Predictions highlight five most likely nuclear proteins and suggest that nuclear roles evolved independently of nuclear access during mitosis. Nuclear localization was confirmed in human cells. These findings suggest that nuclear BBS functions are potentially not restricted to mammals, but may be a common frequently co-opted eukaryotic feature. Understanding the functional spectrum of BBS proteins will help elucidating their role in gene regulation, development, and disease.

Keywords: BBS; Bardet-Biedl Syndrome; Cell biology; Evolutionary biology; Molecular biology; cilia; nucleus.

Associated data

figshare/10.6084/m9.figshare.22140347.v1