Double the Fun, Double the Trouble: Paralogs and Homologs Functioning in the Endoplasmic Reticulum

Annu Rev Biochem. 2020 Jun 20:89:637-666. doi: 10.1146/annurev-biochem-011520-104831.

Abstract

The evolution of eukaryotic genomes has been propelled by a series of gene duplication events, leading to an expansion in new functions and pathways. While duplicate genes may retain some functional redundancy, it is clear that to survive selection they cannot simply serve as a backup but rather must acquire distinct functions required for cellular processes to work accurately and efficiently. Understanding these differences and characterizing gene-specific functions is complex. Here we explore different gene pairs and families within the context of the endoplasmic reticulum (ER), the main cellular hub of lipid biosynthesis and the entry site for the secretory pathway. Focusing on each of the ER functions, we highlight specificities of related proteins and the capabilities conferred to cells through their conservation. More generally, these examples suggest why related genes have been maintained by evolutionary forces and provide a conceptual framework to experimentally determine why they have survived selection.

Keywords: endoplasmic reticulum; gene families; homologs; ohnologs; paralogs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Activating Transcription Factor 6 / genetics
  • Activating Transcription Factor 6 / metabolism
  • Animals
  • Antiporters / genetics
  • Antiporters / metabolism
  • Carboxy-Lyases / genetics
  • Carboxy-Lyases / metabolism
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism*
  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / metabolism
  • Evolution, Molecular*
  • Gene Duplication*
  • HSP40 Heat-Shock Proteins / genetics
  • HSP40 Heat-Shock Proteins / metabolism
  • Hexosyltransferases / genetics
  • Hexosyltransferases / metabolism
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Selection, Genetic*
  • Sphingosine N-Acyltransferase / genetics
  • Sphingosine N-Acyltransferase / metabolism
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism

Substances

  • ATF6 protein, human
  • Activating Transcription Factor 6
  • Antiporters
  • HSP40 Heat-Shock Proteins
  • LTC1 protein, S cerevisiae
  • Membrane Proteins
  • Protein Isoforms
  • SEC24 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Vesicular Transport Proteins
  • Sphingosine N-Acyltransferase
  • Hexosyltransferases
  • dolichyl-diphosphooligosaccharide - protein glycotransferase
  • ERN1 protein, human
  • Protein Serine-Threonine Kinases
  • Endoribonucleases
  • Carboxy-Lyases
  • phosphatidylserine decarboxylase