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Comparative Genomics Reveals Key Gain-of-Function Events in Foxp3 during Regulatory T Cell Evolution

Overview of attention for article published in Frontiers in immunology, January 2012
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Title
Comparative Genomics Reveals Key Gain-of-Function Events in Foxp3 during Regulatory T Cell Evolution
Published in
Frontiers in immunology, January 2012
DOI 10.3389/fimmu.2012.00113
Pubmed ID
Authors

Kristian G. Andersen, Jesper K. Nissen, Alexander G. Betz

Abstract

The immune system has the ability to suppress undesirable responses, such as those against commensal bacteria, food, and paternal antigens in placenta pregnancy. The lineage-specific transcription factor Foxp3 orchestrates the development and function of regulatory T cells underlying this immunological tolerance. Despite the crucial role of Foxp3 in supporting immune homeostasis, little is known about its origin, evolution, and species conservation. We explore these questions using comparative genomics, structural modeling, and functional analyses. Our data reveal that key gain-of-function events occurred during the evolution of Foxp3 in higher vertebrates. We identify key conserved residues in its forkhead domain and show a detailed analysis of the N-terminal region of Foxp3, which is only conserved in mammals. These components are under purifying selection, and our mutational analyses demonstrate that they are essential for Foxp3 function. Our study points to critical functional adaptations in immune tolerance among higher vertebrates, and suggests that Foxp3-mediated transcriptional mechanisms emerged during mammalian evolution as a stepwise gain of functional domains that enabled Foxp3 to interact with a multitude of interaction partners.

Mendeley readers

The data shown below were compiled from readership statistics for 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 2 7%
Mexico 1 4%
United States 1 4%
Unknown 24 86%

Demographic breakdown

Readers by professional status Count As %
Student > Master 10 36%
Student > Ph. D. Student 7 25%
Researcher 7 25%
Lecturer 1 4%
Student > Postgraduate 1 4%
Other 2 7%
Readers by discipline Count As %
Agricultural and Biological Sciences 18 64%
Medicine and Dentistry 5 18%
Computer Science 2 7%
Arts and Humanities 1 4%
Biochemistry, Genetics and Molecular Biology 1 4%
Other 1 4%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 June 2012.
All research outputs
#2,016,642
of 3,628,758 outputs
Outputs from Frontiers in immunology
#748
of 1,224 outputs
Outputs of similar age
#33,629
of 72,175 outputs
Outputs of similar age from Frontiers in immunology
#2
of 3 outputs
Altmetric has tracked 3,628,758 research outputs across all sources so far. This one is in the 25th percentile – i.e., 25% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,224 research outputs from this source. They receive a mean Attention Score of 2.3. This one is in the 3rd percentile – i.e., 3% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 72,175 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 3 others from the same source and published within six weeks on either side of this one.