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김철민

Ghim, Cheol-Min
Physical Biology Biological Physics Lab.
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On a Selective Advantage of Heterozygosity in Regulatory Sequences

Author(s)
Ghim, Cheol-Min
Issued Date
2016-11-23
URI
https://scholarworks.unist.ac.kr/handle/201301/40561
Fulltext
https://www.apctp.org/plan.php/apctp-ictp2016/1579
Citation
APCTP-ICTP Joint Workshop: Quantitative Life Sciences
Abstract
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.
Publisher
Asia Pacific Center for Theoretical Physics

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