In this section
@article{Johnston:2016:10.1016/j.ajhg.2016.09.016,
author = {Johnston, IG and Jones, NS},
doi = {10.1016/j.ajhg.2016.09.016},
journal = {American Journal of Human Genetics},
pages = {1150--1162},
title = {Evolution of cell-to-cell variability in stochastic, controlled, heteroplasmic mtDNA populations},
url = {http://dx.doi.org/10.1016/j.ajhg.2016.09.016},
volume = {99},
year = {2016}
}
TY - JOUR
AB - Populations of physiologically vital mitochondrial DNA (mtDNA) molecules evolve in cells under control from the nucleus. The evolution of populations of mixed mtDNA types is complicated and poorly understood, and variability of these controlled admixtures plays a central role in the inheritance and onset of genetic disease. Here, we develop a mathematical theory describing the evolution of, and variability in, these stochastic populations for any type of cellular control, showing that cell-to-cell variability in mtDNA and mutant load inevitably increases with time, according to rates that we derive and which are notably independent of the mechanistic details of feedback signaling. We show with a set of experimental case studies that this theory explains disparate quantitative results from classical and modern experimental and computational research on heteroplasmy variance in different species. We demonstrate that our general model provides a host of specific insights, including a modification of the often-used but hard-to-interpret Wright formula to correspond directly to biological observables, the ability to quantify selective and mutational pressure in mtDNA populations, and characterization of the pronounced variability inevitably arising from the action of possible mtDNA quality-control mechanisms. Our general theoretical framework, supported by existing experimental results, thus helps us to understand and predict the evolution of stochastic mtDNA populations in cell biology.
AU - Johnston,IG
AU - Jones,NS
DO - 10.1016/j.ajhg.2016.09.016
EP - 1162
PY - 2016///
SN - 1537-6605
SP - 1150
TI - Evolution of cell-to-cell variability in stochastic, controlled, heteroplasmic mtDNA populations
T2 - American Journal of Human Genetics
UR - http://dx.doi.org/10.1016/j.ajhg.2016.09.016
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000387529600012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - http://hdl.handle.net/10044/1/43253
VL - 99
ER -