scholarly journals Endless Conflicts: Detecting Molecular Arms Races in Mammalian Genomes

2019 ◽  
Author(s):  
Jacob C. Cooper ◽  
Christopher J. Leonard ◽  
Brent S. Pedersen ◽  
Clayton M. Carey ◽  
Aaron R. Quinlan ◽  
...  

AbstractRecurrent positive selection at the codon level is often a sign that a gene is engaged in a molecular arms race – a conflict between the genome of its host and the genome of another species over mutually exclusive access to a resource that has a direct effect on the fitness of both individuals. Detecting molecular arms races has led to a better understanding of how evolution changes the molecular interfaces of proteins when organisms compete over time, especially in the realm of host-pathogen interactions. Here, we present a method for detection of gene-level recurrent positive selection across entire genomes for a given phylogenetic group. We deploy this method on five mammalian clades – primates, mice, deer mice, dogs, and bats – to both detect novel instances of recurrent positive selection and to compare the prevalence of recurrent positive selection between clades. We analyze the frequency at which individual genes are targets of recurrent positive selection in multiple clades. We find that coincidence of selection occurs far more frequently than expected by chance, indicating that all clades experience shared selective pressures. Additionally, we highlight Polymeric Immunoglobulin Receptor (PIGR) as a gene which shares specific amino acids under recurrent positive selection in multiple clades, indicating that it has been locked in a molecular arms race for ∼100My. These data provide an in-depth comparison of recurrent positive selection across the mammalian phylogeny, and highlights of the power of comparative evolutionary approaches to generate specific hypotheses about the molecular interactions of rapidly evolving genes.

2018 ◽  
Author(s):  
Jason D Fernandes ◽  
Maximilian Haeussler ◽  
Joel Armstrong ◽  
Kristof Tigyi ◽  
Joshua Gu ◽  
...  

KRAB Zinc Finger Proteins (KZNFs) are the largest and fastest evolving family of human transcription factors1,2. The evolution of this protein family is closely linked to the tempo of retrotransposable element (RTE) invasions, with specific KZNF family members demonstrated to transcriptionally repress specific families of RTEs3,4. The competing selective pressures between RTEs and the KZNFs results in evolutionary arms races whereby KZNFs evolve to recognize RTEs, while RTEs evolve to escape KZNF recognition5. Evolutionary analyses of the primate-specific RTE family L1PA and two of its KZNF binders, ZNF93 and ZNF649, reveal specific nucleotide and amino changes consistent with an arms race scenario. Our results suggest a model whereby ZNF649 and ZNF93 worked together to target independent motifs within the L1PA RTE lineage. L1PA elements eventually escaped the concerted action of this KZNF “team” over ∼30 million years through two distinct mechanisms: a slow accumulation of point mutations in the ZNF649 binding site and a rapid, massive deletion of the entire ZNF93 binding site.


2021 ◽  
Vol 11 (4) ◽  
pp. 309
Author(s):  
Vincenzo Di Leo ◽  
Patrick J. Gleeson ◽  
Fabio Sallustio ◽  
Carine Bounaix ◽  
Jennifer Da Silva ◽  
...  

IgA Nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by the mesangial deposition of abnormally glycosylated IgA1 (Gd-IgA). The production of Gd-IgA occurs in mucose-associated lymphoid tissue (MALT). The microbiota plays a role in MALT modulation. Rifaximin (NORMIX®), a non-absorbable oral antibiotic, induces positive modulation of the gut microbiota, favoring the growth of bacteria beneficial to the host. Here, we evaluate the effect of rifaximin on a humanized mice model of IgAN (α1KI-CD89Tg). Methods: The α1KI-CD89Tg mice were treated by the vehicle (olive oil) or rifaximin (NORMIX®). Serum levels of hIgA, hIgA1–sCD89, and mIgG–hIgA1 immune complexes were determined. Glomerular hIgA1 deposit and CD11b+ cells recruitment were revealed using confocal microscopy. Furthermore, the mRNA of the B-Cell Activating Factor (BAFF), polymeric immunoglobulin receptor (pIgR), and Tumor Necrosing Factor-α (TNF-α) in gut samples were detected by qPCR. Results: Rifaximin treatment decreased the urinary protein-to-creatinine ratio, serum levels of hIgA1–sCD89 and mIgG–hIgA1 complexes, hIgA1 glomerular deposition, and CD11b+ cell infiltration. Moreover, rifaximin treatment decreased significantly BAFF, pIgR, and TNF-α mRNA expression. Conclusions: Rifaximin decreased the IgAN symptoms observed in α1KI-CD89Tg mice, suggesting a possible role for it in the treatment of the disease.


2003 ◽  
Vol 279 (8) ◽  
pp. 6296-6304 ◽  
Author(s):  
Christine Elm ◽  
Ranveig Braathen ◽  
Simone Bergmann ◽  
Ronald Frank ◽  
Jean-Pierre Vaerman ◽  
...  

Cell ◽  
1986 ◽  
Vol 46 (4) ◽  
pp. 613-621 ◽  
Author(s):  
Keith E. Mostov ◽  
David L. Deitcher

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