PMID: 12788232Jun 6, 2003Paper

Effects of epistasis on phenotypic robustness in metabolic pathways

Mathematical Biosciences
Homayoun Bagheri-ChaichianG Wagner

Abstract

It is an open question whether phenomena such as phenotypic robustness to mutation evolve as adaptations or are simply an inherent property of genetic systems. As a case study, we examine this question with regard to dominance in metabolic physiology. Traditionally the conclusion that has been derived from Metabolic Control Analysis has been that dominance is an inevitable property of multi-enzyme systems and hence does not require an evolutionary explanation. This view is based on a mathematical result commonly referred to as the flux summation theorem. However it is shown here that for mutations involving finite changes (of any magnitude) in enzyme concentration, the flux summation theorem can only hold in a very restricted set of conditions. Using both analytical and simulation results we show that for finite changes, the summation theorem is only valid in cases where the relationship between genotype and phenotype is linear and devoid of non-linearities in the form of epistasis. Such an absence of epistasis is unlikely in metabolic systems. As an example, we show that epistasis can arise in scenarios where we assume generic non-linearities such as those caused by enzyme saturation. In such cases dominance levels can be modi...Continue Reading

References

Dec 1, 1975·Journal of Theoretical Biology·D Charlesworth, B Charlesworth
Jan 1, 1992·Bio Systems·S Schuster, R Heinrich
Dec 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·H A Orr
Mar 7, 1991·Journal of Theoretical Biology·H Kacser
Nov 8, 1989·Journal of Theoretical Biology·M A Savageau, A Sorribas
Aug 1, 1986·Genetical Research·A M DeanD L Hartl
Nov 21, 1988·Journal of Theoretical Biology·C Reder
Apr 7, 1987·Journal of Theoretical Biology·A Cornish-Bowden
Jun 21, 1987·Journal of Theoretical Biology·H Kacser
Oct 1, 1987·Genetics·P D Keightley, H Kacser
Nov 1, 1985·Genetics·D L HartlA M Dean
Feb 15, 1974·European Journal of Biochemistry·R Heinrich, T A Rapoport
Dec 1, 1971·Theoretical Population Biology·M W Feldman, S Karlin
Apr 21, 1983·Journal of Theoretical Biology·R Bürger
May 1, 1995·Biochemical Society Transactions·H Kacser, J A Burns
May 1, 1995·Biochemical Society Transactions·H Kacser
Mar 7, 1994·Journal of Theoretical Biology·D R Forsdyke
Sep 7, 1993·Journal of Theoretical Biology·T Höfer, R Heinrich
Sep 1, 1993·European Journal of Biochemistry·H Kacser, L Acerenza
Jan 1, 1993·Trends in Genetics : TIG·J Hodgkin
Jun 1, 1996·Genetics·P D Keightley
Oct 7, 1996·Journal of Theoretical Biology·J W Porteous
Oct 7, 1996·Journal of Theoretical Biology·D L Hartl, C H Taubes
Oct 7, 1996·Journal of Theoretical Biology·P D Keightley
Jun 26, 1997·Nature·N Barkai, S Leibler
Aug 14, 1999·Heredity·D Bourguet
Mar 21, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·G Gibson, G Wagner
Mar 31, 2000·Nature Genetics·A Wagner
Oct 18, 2000·Journal of Theoretical Biology·L Acerenza
Nov 9, 2000·The Journal of Experimental Zoology·L W Ancel, W Fontana
Mar 10, 2001·Science·J L HartmanL Hartwell
Sep 19, 2001·Genetics·M A Gilchrist, H F Nijhout
Jan 31, 2002·Proceedings of the National Academy of Sciences of the United States of America·David C Krakauer, Joshua B Plotkin
Nov 1, 1995·Biophysical Chemistry·B N KholodenkoH V Westerhoff
Jun 1, 1999·The American Naturalist·Sarah P Otto, Denis Bourguet

❮ Previous
Next ❯

Citations

Jan 25, 2005·BMC Evolutionary Biology·Mauro SantosWalkiria Céspedes
May 7, 2011·BMC Systems Biology·Michaël Bekaert, Gavin C Conant
Dec 24, 2010·The Journal of Experimental Biology·Walter F Eanes
Dec 8, 2004·Genetics·Homayoun C Bagheri, Günter P Wagner
Aug 19, 2008·Journal of Theoretical Biology·Paul S Agutter
Nov 29, 2005·Journal of Theoretical Biology·Joseph L McClay, Edwin J C G van den Oord
Sep 15, 2005·Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution·Homayoun C Bagheri
Aug 13, 2021·Biological Reviews of the Cambridge Philosophical Society·Sylvain BilliardViolaine Llaurens

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.