%0 Journal Article %1 tulchinsky2014hybrid %A Tulchinsky, A Y %A Johnson, N A %A Porter, A H %D 2014 %J Genetics %K GRN constraint genotype-phenotype hybrid_incompatibility pleiotropy selection simulation speciation transcription_regulation %N 4 %P 1645-1654 %R 10.1534/genetics.114.171397 %T Hybrid incompatibility despite pleiotropic constraint in a sequence-based bioenergetic model of transcription factor binding %U http://www.ncbi.nlm.nih.gov/pubmed/25313130 %V 198 %X Hybrid incompatibility can result from gene misregulation produced by divergence in trans-acting regulatory factors and their cis-regulatory targets. However, change in trans-acting factors may be constrained by pleiotropy, which would in turn limit the evolution of incompatibility. We employed a mechanistically explicit bioenergetic model of gene expression wherein parameter combinations (number of transcription factor molecules, energetic properties of binding to the regulatory site, and genomic background size) determine the shape of the genotype-phenotype (G-P) map, and interacting allelic variants of mutable cis and trans sites determine the phenotype along that map. Misregulation occurs when the phenotype differs from its optimal value. We simulated a pleiotropic regulatory pathway involving a positively selected and a conserved trait regulated by a shared transcription factor (TF), with two populations evolving in parallel. Pleiotropic constraints shifted evolution in the positively selected trait to its cis-regulatory locus. We nevertheless found that the TF genotypes often evolved, accompanied by compensatory evolution in the conserved trait, and both traits contributed to hybrid misregulation. Compensatory evolution resulted in "developmental system drift," whereby the regulatory basis of the conserved phenotype changed although the phenotype itself did not. Pleiotropic constraints became stronger and in some cases prohibitive when the bioenergetic properties of the molecular interaction produced a G-P map that was too steep. Likewise, compensatory evolution slowed and hybrid misregulation was not evident when the G-P map was too shallow. A broad pleiotropic "sweet spot" nevertheless existed where evolutionary constraints were moderate to weak, permitting substantial hybrid misregulation in both traits. None of these pleiotropic constraints manifested when the TF contained nonrecombining domains independently regulating the respective traits.

@article{tulchinsky2014hybrid, abstract = {Hybrid incompatibility can result from gene misregulation produced by divergence in trans-acting regulatory factors and their cis-regulatory targets. However, change in trans-acting factors may be constrained by pleiotropy, which would in turn limit the evolution of incompatibility. We employed a mechanistically explicit bioenergetic model of gene expression wherein parameter combinations (number of transcription factor molecules, energetic properties of binding to the regulatory site, and genomic background size) determine the shape of the genotype-phenotype (G-P) map, and interacting allelic variants of mutable cis and trans sites determine the phenotype along that map. Misregulation occurs when the phenotype differs from its optimal value. We simulated a pleiotropic regulatory pathway involving a positively selected and a conserved trait regulated by a shared transcription factor (TF), with two populations evolving in parallel. Pleiotropic constraints shifted evolution in the positively selected trait to its cis-regulatory locus. We nevertheless found that the TF genotypes often evolved, accompanied by compensatory evolution in the conserved trait, and both traits contributed to hybrid misregulation. Compensatory evolution resulted in "developmental system drift," whereby the regulatory basis of the conserved phenotype changed although the phenotype itself did not. Pleiotropic constraints became stronger and in some cases prohibitive when the bioenergetic properties of the molecular interaction produced a G-P map that was too steep. Likewise, compensatory evolution slowed and hybrid misregulation was not evident when the G-P map was too shallow. A broad pleiotropic "sweet spot" nevertheless existed where evolutionary constraints were moderate to weak, permitting substantial hybrid misregulation in both traits. None of these pleiotropic constraints manifested when the TF contained nonrecombining domains independently regulating the respective traits.}, added-at = {2015-02-23T01:50:56.000+0100}, author = {Tulchinsky, A Y and Johnson, N A and Porter, A H}, biburl = {https://www.bibsonomy.org/bibtex/268d7521a2e006b7545c01783435e8f05/peter.ralph}, doi = {10.1534/genetics.114.171397}, interhash = {2059766f8666722ad8a566675e855c7c}, intrahash = {68d7521a2e006b7545c01783435e8f05}, journal = {Genetics}, keywords = {GRN constraint genotype-phenotype hybrid_incompatibility pleiotropy selection simulation speciation transcription_regulation}, month = dec, number = 4, pages = {1645-1654}, pmid = {25313130}, timestamp = {2015-02-23T01:50:56.000+0100}, title = {Hybrid incompatibility despite pleiotropic constraint in a sequence-based bioenergetic model of transcription factor binding}, url = {http://www.ncbi.nlm.nih.gov/pubmed/25313130}, volume = 198, year = 2014 }