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

2020 ◽  
Vol 89 (1) ◽  
pp. 637-666
Author(s):  
Emma J. Fenech ◽  
Shifra Ben-Dor ◽  
Maya Schuldiner
Keyword(s):  
Endoplasmic Reticulum ◽  
Gene Duplication ◽  
Secretory Pathway ◽  
Duplicate Genes ◽  
Entry Site ◽  
Cellular Processes ◽  
Evolutionary Forces ◽  
Duplication Events ◽  
Related Proteins ◽  
Eukaryotic Genomes

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.

scholarly journals Enhanced functional divergence of duplicate genes several million years after gene duplication in the Arabidopsis lineage

2016 ◽  
Author(s):  
Kousuke Hanada ◽  
Ayumi Tezuka ◽  
Masafumi Nozawa ◽  
Yutaka Suzuki ◽  
Sumio Sugano ◽  
...  
Keyword(s):  
Gene Duplication ◽  
Functional Divergence ◽  
Purifying Selection ◽  
Orthologous Gene ◽  
Synonymous Substitution ◽  
Duplicate Genes ◽  
Duplicated Genes ◽  
Highly Qualified ◽  
Duplication Events ◽  
Synonymous Substitution Rates

AbstractLineage-specifically duplicated genes likely contribute to the phenotypic divergence in closely related species. However, neither the frequency of duplication events nor the degree of selective pressures immediately after gene duplication is clear in the speciation process. Plants have substantially higher gene duplication rates than most other eukaryotes. Here, using Illumina short reads from Arabidopsis halleri, which has highly qualified plant genomes in close species (Brassica rapa, A. thaliana and A. lyrata), we succeeded in generating orthologous gene groups among B. rapa, A. thaliana, A. lyrata and A. halleri. The frequency of duplication events in the Arabidopsis lineage was approximately 10 times higher than the frequency inferred by comparative genomics of Arabidopsis, poplar, rice and moss. Of the currently retained genes in A. halleri, 11–24% had undergone gene duplication in the Arabidopsis lineage. To examine the degree of selective pressure for duplicated genes, we calculated the ratios of nonsynonymous to synonymous substitution rates (KA/KS) in the A. halleri-lyrata and A. halleri lineages. Using a maximum-likelihood framework, we examined positive (KA/KS > 1) and purifying selection (KA/KS < 1) at a significant level (P < 0.01). Duplicate genes tended to have a higher proportion of positive selection compared with non-duplicated genes. More interestingly, we found that functional divergence of duplicated genes was accelerated several million years after gene duplication at a higher proportion than immediately after gene duplication.

scholarly journals An evolving paradigm for the secretory pathway?

2011 ◽  
Vol 22 (21) ◽  
pp. 3929-3932 ◽  
Author(s):  
Jennifer Lippincott-Schwartz
Keyword(s):  
Endoplasmic Reticulum ◽  
Secretory Pathway ◽  
New Technologies ◽  
Fluorescent Protein ◽  
Subsequent Development ◽  
Dynamic Processes ◽  
Genetic Studies ◽  
Cellular Processes ◽  
Transport Vesicles ◽  
Green Fluorescent

The paradigm that the secretory pathway consists of a stable endoplasmic reticulum and Golgi apparatus, using discrete transport vesicles to exchange their contents, gained important support from groundbreaking biochemical and genetic studies during the 1980s. However, the subsequent development of new imaging technologies with green fluorescent protein introduced data on dynamic processes not fully accounted for by the paradigm. As a result, we may be seeing an example of how a paradigm is evolving to account for the results of new technologies and their new ways of describing cellular processes.

scholarly journals HSDFinder: A BLAST-Based Strategy for Identifying Highly Similar Duplicated Genes in Eukaryotic Genomes

2021 ◽  
Vol 1 ◽  
Author(s):  
Xi Zhang ◽  
Yining Hu ◽  
David Roy Smith
Keyword(s):  
Gene Duplication ◽  
Genetic Material ◽  
Duplicate Genes ◽  
Functional Categories ◽  
Web Tool ◽  
Eukaryotic Species ◽  
External Software ◽  
Multiple Species ◽  
User Friendly ◽  
Eukaryotic Genomes

Gene duplication is an important evolutionary mechanism capable of providing new genetic material for adaptive and nonadaptive evolution. However, bioinformatics tools for identifying duplicate genes are often limited to the detection of paralogs in multiple species or to specific types of gene duplicates, such as retrocopies. Here, we present a user-friendly, BLAST-based web tool, called HSDFinder, which can identify, annotate, categorize, and visualize highly similar duplicate genes (HSDs) in eukaryotic nuclear genomes. HSDFinder includes an online heatmap plotting option, allowing users to compare HSDs among different species and visualize the results in different Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway functional categories. The external software requirements are BLAST, InterProScan, and KEGG. The utility of HSDFinder was tested on various model eukaryotic species, including Chlamydomonas reinhardtii, Arabidopsis thaliana, Oryza sativa, and Zea mays as well as the psychrophilic green alga Chlamydomonas sp. UWO241, and was proven to be a practical and accurate tool for gene duplication analyses. The web tool is free to use at http://hsdfinder.com. Documentation and tutorials can be found via the GitHub: https://github.com/zx0223winner/HSDFinder.

Testicular Injury Attenuated by Rapamycin Through Induction of Autophagy and Inhibition of Endoplasmic Reticulum Stress in Streptozotocin- Induced Diabetic Rats

2019 ◽  
Vol 19 (5) ◽  
pp. 665-675 ◽  
Author(s):  
Wenjiao Shi ◽  
Zhixin Guo ◽  
Ruixia Yuan
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protective Effect ◽  
Er Stress ◽  
B Cell Lymphoma ◽  
Diabetic Rats ◽  
Pathological Changes ◽  
Rapamycin Treatment ◽  
Related Proteins

Background and Objective: This study investigated whether rapamycin has a protective effect on the testis of diabetic rats by regulating autophagy, endoplasmic reticulum stress, and oxidative stress. Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups: control, diabetic, and diabetic treated with rapamycin, which received gavage of rapamycin (2mg.kg-1.d-1) after induction of diabetes. Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 65mg.Kg-1). All rats were sacrificed at the termination after 8 weeks of rapamycin treatment. The testicular pathological changes were determined by hematoxylin and eosin staining. The protein or mRNA expression of autophagy-related proteins (Beclin1, microtubule-associated protein light chain 3 (LC3), p62), ER stress marked proteins (CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), caspase-12), oxidative stress-related proteins (p22phox, nuclear factor erythroid2-related factor 2 (Nrf2)) and apoptosis-related proteins (Bax, B cell lymphoma-2 (Bcl-2)) were assayed by western blot or real-time fluorescence quantitative PCR. Results: There were significant pathological changes in the testes of diabetic rats. The expression of Beclin1, LC3, Nrf2, Bcl-2 were significantly decreased and p62, CHOP, caspase12, p22phox, and Bax were notably increased in the testis of diabetic rats (P <0.05). However, rapamycin treatment for 8 weeks significantly reversed the above changes in the testis of diabetic rats (P <0.05). Conclusion: Rapamycin appears to produce a protective effect on the testes of diabetic rats by inducing the expression of autophagy and inhibiting the expression of ER-stress, oxidative stress, and apoptosis.

scholarly journals Ceramide chain length–dependent protein sorting into selective endoplasmic reticulum exit sites

2020 ◽  
Vol 6 (50) ◽  
pp. eaba8237
Author(s):  
Sofia Rodriguez-Gallardo ◽  
Kazuo Kurokawa ◽  
Susana Sabido-Bozo ◽  
Alejandro Cortes-Gomez ◽  
Atsuko Ikeda ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Chain Length ◽  
Secretory Pathway ◽  
Protein Sorting ◽  
Endoplasmic Reticulum Membrane ◽  
Lipid Chain ◽  
Secretory Transport ◽  
Dependent Protein ◽  
Cellular Compartmentalization

Protein sorting in the secretory pathway is crucial to maintain cellular compartmentalization and homeostasis. In addition to coat-mediated sorting, the role of lipids in driving protein sorting during secretory transport is a longstanding fundamental question that still remains unanswered. Here, we conduct 3D simultaneous multicolor high-resolution live imaging to demonstrate in vivo that newly synthesized glycosylphosphatidylinositol-anchored proteins having a very long chain ceramide lipid moiety are clustered and sorted into specialized endoplasmic reticulum exit sites that are distinct from those used by transmembrane proteins. Furthermore, we show that the chain length of ceramide in the endoplasmic reticulum membrane is critical for this sorting selectivity. Our study provides the first direct in vivo evidence for lipid chain length–based protein cargo sorting into selective export sites of the secretory pathway.

Systematic evidence from gene duplication and regulation

1990 ◽  
Vol 3 (1) ◽  
pp. 145
Author(s):  
DJ Colgan
Keyword(s):  
Gene Duplication ◽  
Evolutionary History ◽  
Tandem Duplication ◽  
Fragment Length Polymorphism ◽  
Duplicate Genes ◽  
Polymorphism Analysis ◽  
Multiple Origins ◽  
The Family ◽  
History Of ◽  
Phylogenetic Hypotheses

This paper is a review of the use of information regarding the presence of duplicate genes and their regulation in systematics. The review concentrates on data derived from protein electrophoresis and restriction fragment length polymorphism analysis. The appearance of a duplication in a subset of a group of species implies that the members of the subset belong to the same clade. Suppression of the duplication may render this clade apparently paraphyletic, but may itself be informative of relations within the lineage through patterns of loss of expression in all, or some tissues, or through restrictions of the formation of functional heteropolymers in polymeric enzymes. Examples are given of studies which have used such information to establish phylogenetic hypotheses at the family level, to identify an auto- or allo-polyploid origin of polyploid species and to determine whether there have been single or multiple origins of such species. The likelihood of homoplasy in the patterns of appearance and regulation of duplicates depends on the molecular basis of the duplication. In particular, the contrast between the expected consequences of tandem duplication and the expression of pseudogenes emphasises the value of determining the mechanism of the original duplication. Many instances of sporadic gene duplication are now known, and polyploidisation is a common event in the evolutionary history of both plants and animals. So the opportunities to discover duplicationrelated characters will arise in many systematic studies. A program is presented to increase the chances that such useful information will be recognisable during the studies.

scholarly journals The unfolded protein response coordinates the production of endoplasmic reticulum protein and endoplasmic reticulum membrane.

1997 ◽  
Vol 8 (9) ◽  
pp. 1805-1814 ◽  
Author(s):  
J S Cox ◽  
R E Chapman ◽  
P Walter
Keyword(s):  
Endoplasmic Reticulum ◽  
Unfolded Protein Response ◽  
Secretory Pathway ◽  
Lipid Synthesis ◽  
Secretory Proteins ◽  
Endoplasmic Reticulum Membrane ◽  
Yeast Saccharomyces Cerevisiae ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

The endoplasmic reticulum (ER) is a multifunctional organelle responsible for production of both lumenal and membrane components of secretory pathway compartments. Secretory proteins are folded, processed, and sorted in the ER lumen and lipid synthesis occurs on the ER membrane itself. In the yeast Saccharomyces cerevisiae, synthesis of ER components is highly regulated: the ER-resident proteins by the unfolded protein response and membrane lipid synthesis by the inositol response. We demonstrate that these two responses are intimately linked, forming different branches of the same pathway. Furthermore, we present evidence indicating that this coordinate regulation plays a role in ER biogenesis.

scholarly journals The EF-Hand Ca2+-binding Protein p22 Plays a Role in Microtubule and Endoplasmic Reticulum Organization and Dynamics with Distinct Ca2+-binding Requirements

2004 ◽  
Vol 15 (2) ◽  
pp. 481-496 ◽  
Author(s):  
Josefa Andrade ◽  
Hu Zhao ◽  
Brian Titus ◽  
Sandra Timm Pearce ◽  
Margarida Barroso
Keyword(s):  
Endoplasmic Reticulum ◽  
Conformational Changes ◽  
Membrane Trafficking ◽  
Secretory Pathway ◽  
Network Formation ◽  
Binding Protein ◽  
Dependent Manner ◽  
Microtubule Depolymerization ◽  
Independent Manner ◽  
Ef Hand

We have reported that p22, an N-myristoylated EF-hand Ca2+-binding protein, associates with microtubules and plays a role in membrane trafficking. Here, we show that p22 also associates with membranes of the early secretory pathway membranes, in particular endoplasmic reticulum (ER). On binding of Ca2+, p22's ability to associate with membranes increases in an N-myristoylation-dependent manner, which is suggestive of a nonclassical Ca2+-myristoyl switch mechanism. To address the intracellular functions of p22, a digitonin-based “bulk microinjection” assay was developed to load cells with anti-p22, wild-type, or mutant p22 proteins. Antibodies against a p22 peptide induce microtubule depolymerization and ER fragmentation; this antibody-mediated effect is overcome by preincubation with the respective p22 peptide. In contrast, N-myristoylated p22 induces the formation of microtubule bundles, the accumulation of ER structures along the bundles as well as an increase in ER network formation. An N-myristoylated Ca2+-binding p22 mutant, which is unable to undergo Ca2+-mediated conformational changes, induces microtubule bundling and accumulation of ER structures along the bundles but does not increase ER network formation. Together, these data strongly suggest that p22 modulates the organization and dynamics of microtubule cytoskeleton in a Ca2+-independent manner and affects ER network assembly in a Ca2+-dependent manner.

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