Abstract

PEX genes encode proteins involved in peroxisome biogenesis and proliferation. Using a comparative genomics approach, we clarify the evolutionary relationships between the 37 known PEX proteins in a representative set of eukaryotes, including all common model organisms, pathogenic unicellular eukaryotes and human. A large number of previously unknown PEX orthologs were identified. We analyzed all PEX proteins, their conservation and domain architecture and defined the core set of PEX proteins that is required to make a peroxisome. The molecular processes in peroxisome biogenesis in different organisms were put into context, showing that peroxisomes are not static organelles in eukaryotic evolution. Organisms that lack peroxisomes still contain a few PEX proteins, which probably play a role in alternative processes. Finally, the relationships between PEX proteins of two large families, the Pex11 and Pex23 families, were analyzed, thereby contributing to the understanding of their complicated and sometimes incorrect nomenclature. We provide an exhaustive overview of this important eukaryotic organelle.

Highlights

  • IntroductionTheir number, size and protein composition are highly variable

  • We used a comparative genomics approach to provide an upto-date overview of all PEX protein families identified so far, in a range of representative organisms from distant eukaryotic lineages, including many model organisms that are currently extensively used in cell biology research

  • In agreement with previous studies, our computational survey identified a core set of PEX proteins that is broadly conserved across distant eukaryotic lineages (PEX1/2/3/5/10/12/14/19 (Gabaldón et al, 2006; Schlüter et al, 2006) and in addition PEX6/7/11/13/16, this study)

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Summary

Introduction

Their number, size and protein composition are highly variable. In lower eukaryotes, such as yeast, peroxisome proliferation is stimulated by specific growth substrates. Peroxisome abundance and composition vary with organism, tissue and developmental stage. Conserved peroxisomal pathways are the β-oxidation of fatty acids and hydrogen peroxide degradation. The crucial role of peroxisomes for human health is illustrated by the occurrence of inborn errors that cause severe diseases and are often lethal. Roles in non-metabolic processes such as aging, anti-viral defense and cancer show that the significance of peroxisomes in human health goes far beyond the relatively rare inherited peroxisomal disorders (Islinger et al, 2018)

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