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Selected heterozygosity at cis-regulatory sequences increases the expression homogeneity of a cell population in humans

Overview of attention for article published in Genome Biology (Online Edition), July 2016
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Citations

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Title
Selected heterozygosity at cis-regulatory sequences increases the expression homogeneity of a cell population in humans
Published in
Genome Biology (Online Edition), July 2016
DOI 10.1186/s13059-016-1027-8
Pubmed ID
Authors

Min Kyung Sung, Juneil Jang, Kang Seon Lee, Cheol-Min Ghim, Jung Kyoon Choi

Abstract

Examples of heterozygote advantage in humans are scarce and limited to protein-coding sequences. Here, we attempt a genome-wide functional inference of advantageous heterozygosity at cis-regulatory regions. The single-nucleotide polymorphisms bearing the signatures of balancing selection are enriched in active cis-regulatory regions of immune cells and epithelial cells, the latter of which provide barrier function and innate immunity. Examples associated with ancient trans-specific balancing selection are also discovered. Allelic imbalance in chromatin accessibility and divergence in transcription factor motif sequences indicate that these balanced polymorphisms cause distinct regulatory variation. However, a majority of these variants show no association with the expression level of the target gene. Instead, single-cell experimental data for gene expression and chromatin accessibility demonstrate that heterozygous sequences can lower cell-to-cell variability in proportion to selection strengths. This negative correlation is more pronounced for highly expressed genes and consistently observed when using different data and methods. Based on mathematical modeling, we hypothesize that extrinsic noise from fluctuations in transcription factor activity may be amplified in homozygotes, whereas it is buffered in heterozygotes. While high expression levels are coupled with intrinsic noise reduction, regulatory heterozygosity can contribute to the suppression of extrinsic noise. This mechanism may confer a selective advantage by increasing cell population homogeneity and thereby enhancing the collective action of the cells, especially of those involved in the defense systems in humans.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
France 1 3%
Brazil 1 3%
Unknown 34 94%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 22%
Student > Bachelor 5 14%
Professor 4 11%
Student > Postgraduate 3 8%
Other 3 8%
Other 9 25%
Unknown 4 11%
Readers by discipline Count As %
Agricultural and Biological Sciences 15 42%
Biochemistry, Genetics and Molecular Biology 9 25%
Engineering 2 6%
Computer Science 2 6%
Medicine and Dentistry 1 3%
Other 1 3%
Unknown 6 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 16 September 2016.
All research outputs
#3,981,122
of 8,386,076 outputs
Outputs from Genome Biology (Online Edition)
#2,034
of 2,368 outputs
Outputs of similar age
#119,381
of 260,175 outputs
Outputs of similar age from Genome Biology (Online Edition)
#50
of 58 outputs
Altmetric has tracked 8,386,076 research outputs across all sources so far. This one has received more attention than most of these and is in the 50th percentile.
So far Altmetric has tracked 2,368 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 21.8. This one is in the 13th percentile – i.e., 13% 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 260,175 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.
We're also able to compare this research output to 58 others from the same source and published within six weeks on either side of this one. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.