Format

Send to

Choose Destination
PLoS One. 2015 Apr 13;10(4):e0120785. doi: 10.1371/journal.pone.0120785. eCollection 2015.

Regulatory evolution and voltage-gated ion channel expression in squid axon: selection-mutation balance and fitness cliffs.

Author information

1
Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, New York, United States of America.
2
Institute of Molecular Cardiology, Stony Brook University, Stony Brook, New York, United States of America.
3
Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York, United States of America.
4
Institute of Molecular Cardiology, Stony Brook University, Stony Brook, New York, United States of America; Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York, United States of America.
5
Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, New York, United States of America; Institute of Molecular Cardiology, Stony Brook University, Stony Brook, New York, United States of America; The Department of Research, Veterans Affairs Medical Center, Northport, New York, United States of America.

Abstract

It has been suggested that optimization of either axonal conduction velocity or the energy efficiency of action potential conduction predominates in the selection of voltage-gated sodium conductance levels in the squid axon. A population genetics model of channel gene regulatory function was used to examine the role of these and other evolutionary forces on the selection of both sodium and potassium channel expression levels. In this model, the accumulating effects of mutations result in degradation of gene regulatory function, causing channel gene expression to fall to near-zero in the absence of positive selection. In the presence of positive selection, channel expression levels fall to the lowest values consistent with the selection criteria, thereby establishing a selection-mutation balance. Within the parameter space of sodium and potassium conductance values, the physiological performance of the squid axon model showed marked discontinuities associated with conduction failure and excitability. These discontinuities in physiological function may produce fitness cliffs. A fitness cliff associated with conduction failure, combined with the effects of phenotypic noise, can account for the selection of sodium conductance levels, without considering either conduction velocity or metabolic cost. A fitness cliff associated with a transition in axonal excitability, combined with phenotypic noise, can explain the selection of potassium channel expression levels. The results suggest that voltage-gated ion channel expression will fall to low levels, consistent with key functional constraints, even in the absence of positive selection for energy efficiency. Channel expression levels and individual variation in channel expression within the population can be explained by regulatory evolution in combination with genetic variation in regulatory function and phenotypic noise, without resorting to more complex mechanisms, such as activity-dependent homeostasis. Only a relatively small region of the large, nominally isofunctional parameter space for channel expression will normally be occupied, because of the effects of mutation.

PMID:
25875483
PMCID:
PMC4395378
DOI:
10.1371/journal.pone.0120785
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center