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Evolution of the highly networked deubiquitinating enzymes USP4, USP15, and USP11

Overview of attention for article published in BMC Ecology and Evolution, October 2015
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Title
Evolution of the highly networked deubiquitinating enzymes USP4, USP15, and USP11
Published in
BMC Ecology and Evolution, October 2015
DOI 10.1186/s12862-015-0511-1
Pubmed ID
Authors

Caitlyn Vlasschaert, Xuhua Xia, Josée Coulombe, Douglas A. Gray

Abstract

USP4, USP15 and USP11 are paralogous deubiquitinating enzymes as evidenced by structural organization and sequence similarity. Based on known interactions and substrates it would appear that they have partially redundant roles in pathways vital to cell proliferation, development and innate immunity, and elevated expression of all three has been reported in various human malignancies. The nature and order of duplication events that gave rise to these extant genes has not been determined, nor has their functional redundancy been established experimentally at the organismal level. We have employed phylogenetic and syntenic reconstruction methods to determine the chronology of the duplication events that generated the three paralogs and have performed genetic crosses to evaluate redundancy in mice. Our analyses indicate that USP4 and USP15 arose from whole genome duplication prior to the emergence of jawed vertebrates. Despite having lower sequence identity USP11 was generated later in vertebrate evolution by small-scale duplication of the USP4-encoding region. While USP11 was subsequently lost in many vertebrate species, all available genomes retain a functional copy of either USP4 or USP15, and through genetic crosses of mice with inactivating mutations we have confirmed that viability is contingent on a functional copy of USP4 or USP15. Loss of ubiquitin-exchange regulation, constitutive skipping of the seventh exon and neural-specific expression patterns are derived states of USP11. Post-translational modification sites differ between USP4, USP15 and USP11 throughout evolution. In isolation sequence alignments can generate erroneous USP gene phylogenies. Through a combination of methodologies the gene duplication events that gave rise to USP4, USP15, and USP11 have been established. Although it operates in the same molecular pathways as the other USPs, the rapid divergence of the more recently generated USP11 enzyme precludes its functional interchangeability with USP4 and USP15. Given their multiplicity of substrates the emergence (and in some cases subsequent loss) of these USP paralogs would be expected to alter the dynamics of the networks in which they are embedded.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Unknown 50 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 14%
Researcher 6 12%
Student > Bachelor 5 10%
Student > Doctoral Student 4 8%
Student > Postgraduate 4 8%
Other 6 12%
Unknown 19 37%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 29%
Agricultural and Biological Sciences 5 10%
Medicine and Dentistry 3 6%
Chemistry 3 6%
Neuroscience 2 4%
Other 3 6%
Unknown 20 39%
Attention Score in Context

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 28 October 2015.
All research outputs
#17,285,036
of 25,373,627 outputs
Outputs from BMC Ecology and Evolution
#2,928
of 3,714 outputs
Outputs of similar age
#176,900
of 295,169 outputs
Outputs of similar age from BMC Ecology and Evolution
#62
of 79 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,714 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.5. This one is in the 14th percentile – i.e., 14% of its peers scored the same or lower than it.
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We're also able to compare this research output to 79 others from the same source and published within six weeks on either side of this one. This one is in the 20th percentile – i.e., 20% of its contemporaries scored the same or lower than it.