The evolution of zebrafish RAG2 protein is required for adapting to the elevated body temperature of the higher endothermic vertebrates.

Scientific Reports
Ao SunXiaolong Liu

Abstract

The recombination activating gene (RAG or RAG1/RAG2 complex)-mediated adaptive immune system is a hallmark of jawed vertebrates. It has been reported that RAG originated in invertebrates. However, whether RAG further evolved once it arose in jawed vertebrates remains largely unknown. Here, we found that zebrafish RAG (zRAG) had a lower activity than mouse RAG (mRAG). Intriguingly, the attenuated stability of zebrafish RAG2 (zRAG2), but not zebrafish RAG1, caused the reduced V(D)J recombination efficiency compared to mRAG at 37 °C which are the body temperature of most endotherms except birds. Importantly, the lower temperature 28 °C, which is the best temperature for zebrafish growth, made the recombination efficiency of zRAG similar to that of mRAG by improving the stability of zRAG2. Consistent with the prementioned observation, the V(D)J recombination of Rag2KI/KI mice, which zRAG2 was substituted for mRAG2, was also severely impaired. Unexpectedly, Rag2KI/KI mice developed cachexia syndromes accompanied by premature death. Taken together, our findings illustrate that the evolution of zebrafish RAG2 protein is required for adapting to the elevated body temperature of the higher endothermic vertebrates.

References

Apr 14, 1983·Nature·S Tonegawa
Apr 17, 1999·Molecular and Cellular Biology·P C Swanson, S Desiderio
May 19, 2001·Methods in Molecular Biology·R G Caldwell, R Longnecker
Jan 20, 2005·The Journal of Experimental Medicine·Claire L LangrishDaniel J Cua
Nov 2, 2005·Nature Reviews. Immunology·Gary W LitmanLarry J Dishaw
Feb 25, 2006·Cell·Max D Cooper, Matthew N Alder
Mar 16, 2006·Proceedings. Biological Sciences·Frank SeebacherMichael B Thompson
Apr 19, 2007·Nature Reviews. Genetics·Graham J Lieschke, Peter D Currie
Sep 28, 2007·Nature·Barbara CorneoDavid B Roth
Nov 29, 2007·Zebrafish·Raymond E EngeszerDavid M Parichy
Dec 14, 2007·Nature·John Kuriyan, David Eisenberg
May 27, 2008·Nature Immunology·Xiaoming WangXiaolong Liu
Jul 22, 2008·Nature Chemical Biology·Nina M Goodey, Stephen J Benkovic
Sep 22, 2009·Current Opinion in Structural Biology·Nobuhiko Tokuriki, Dan S Tawfik
Dec 10, 2009·Nature Reviews. Genetics·Martin F Flajnik, Masanori Kasahara
Jun 29, 2010·European Journal of Immunology·Akihiro Kimura, Tadamitsu Kishimoto
Dec 3, 2010·Proceedings of the National Academy of Sciences of the United States of America·Cosmas C GiallourakisFrederick W Alt
Mar 12, 2011·Nature Reviews. Immunology·David G Schatz, Yanhong Ji
Aug 23, 2011·Annual Review of Genetics·David G Schatz, Patrick C Swanson
Sep 13, 2011·Nature·Chunguang GuoFrederick W Alt
Nov 19, 2011·Nature Reviews. Immunology·Kingston H G Mills
Dec 27, 2011·Cell·Kimberly A ReynoldsRama Ranganathan
Sep 6, 2012·Proceedings of the National Academy of Sciences of the United States of America·Gang XiaoXiaolong Liu
Oct 16, 2012·Nature·Michael S BreenFyodor A Kondrashov
Jun 22, 2013·Molecular Cancer Research : MCR·Aaron LaineTej K Pandita
Dec 26, 2013·Proceedings of the National Academy of Sciences of the United States of America·Yanni ZhangXiaolong Liu
Oct 9, 2014·Frontiers in Immunology·Kurt Buchmann
Nov 11, 2014·Annual Review of Animal Biosciences·Thomas Boehm, Jeremy B Swann
Feb 25, 2015·Nature·Min-Sung KimMartin Gellert
Apr 24, 2015·Nature·Martin D Brazeau, Matt Friedman
Aug 4, 2015·Cell·Grace TengDavid G Schatz
Oct 20, 2015·Advances in Immunology·Grace Teng, David G Schatz
Dec 23, 2015·European Journal of Immunology·Ke XuXiaolong Liu
Feb 24, 2016·Oncogenesis·P E Porporato
Mar 22, 2016·Nature Reviews. Immunology·Luigi D NotarangeloYu Nee Lee

❮ Previous
Next ❯

Citations

Oct 14, 2021·Cell Reports·Tingting GanJiazhi Hu

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
transfection
flow cytometry
FACS
PMA
genotyping

Software Mentioned

FlowJo

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Advances in Experimental Medicine and Biology
Adam G W Matthews, M A Oettinger
Genome Biology and Evolution
D Passagem-SantosJ B Pereira-Leal
© 2021 Meta ULC. All rights reserved