A functionally divergent intrinsically disordered region underlying the conservation of stochastic signaling.

Stochastic signaling dynamics expand living cells' information processing capabilities. An increasing number of studies report that regulators encode information in their pulsatile dynamics. The evolutionary mechanisms that lead to complex signaling dynamics remain uncharacterized, perhaps beca...

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Autores principales:	Ian S Hsu, Bob Strome, Emma Lash, Nicole Robbins, Leah E Cowen, Alan M Moses
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/fc43d48845f1409795c80b3a2d11b345
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spelling	oai:doaj.org-article:fc43d48845f1409795c80b3a2d11b3452021-12-02T20:03:03ZA functionally divergent intrinsically disordered region underlying the conservation of stochastic signaling.1553-73901553-740410.1371/journal.pgen.1009629https://doaj.org/article/fc43d48845f1409795c80b3a2d11b3452021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009629https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Stochastic signaling dynamics expand living cells' information processing capabilities. An increasing number of studies report that regulators encode information in their pulsatile dynamics. The evolutionary mechanisms that lead to complex signaling dynamics remain uncharacterized, perhaps because key interactions of signaling proteins are encoded in intrinsically disordered regions (IDRs), whose evolution is difficult to analyze. Here we focused on the IDR that controls the stochastic pulsing dynamics of Crz1, a transcription factor in fungi downstream of the widely conserved calcium signaling pathway. We find that Crz1 IDRs from anciently diverged fungi can all respond transiently to calcium stress; however, only Crz1 IDRs from the Saccharomyces clade support pulsatility, encode extra information, and rescue fitness in competition assays, while the Crz1 IDRs from distantly related fungi do none of the three. On the other hand, we find that Crz1 pulsing is conserved in the distantly related fungi, consistent with the evolutionary model of stabilizing selection on the signaling phenotype. Further, we show that a calcineurin docking site in a specific part of the IDRs appears to be sufficient for pulsing and show evidence for a beneficial increase in the relative calcineurin affinity of this docking site. We propose that evolutionary flexibility of functionally divergent IDRs underlies the conservation of stochastic signaling by stabilizing selection.Ian S HsuBob StromeEmma LashNicole RobbinsLeah E CowenAlan M MosesPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 9, p e1009629 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Ian S Hsu Bob Strome Emma Lash Nicole Robbins Leah E Cowen Alan M Moses A functionally divergent intrinsically disordered region underlying the conservation of stochastic signaling.
description	Stochastic signaling dynamics expand living cells' information processing capabilities. An increasing number of studies report that regulators encode information in their pulsatile dynamics. The evolutionary mechanisms that lead to complex signaling dynamics remain uncharacterized, perhaps because key interactions of signaling proteins are encoded in intrinsically disordered regions (IDRs), whose evolution is difficult to analyze. Here we focused on the IDR that controls the stochastic pulsing dynamics of Crz1, a transcription factor in fungi downstream of the widely conserved calcium signaling pathway. We find that Crz1 IDRs from anciently diverged fungi can all respond transiently to calcium stress; however, only Crz1 IDRs from the Saccharomyces clade support pulsatility, encode extra information, and rescue fitness in competition assays, while the Crz1 IDRs from distantly related fungi do none of the three. On the other hand, we find that Crz1 pulsing is conserved in the distantly related fungi, consistent with the evolutionary model of stabilizing selection on the signaling phenotype. Further, we show that a calcineurin docking site in a specific part of the IDRs appears to be sufficient for pulsing and show evidence for a beneficial increase in the relative calcineurin affinity of this docking site. We propose that evolutionary flexibility of functionally divergent IDRs underlies the conservation of stochastic signaling by stabilizing selection.
format	article
author	Ian S Hsu Bob Strome Emma Lash Nicole Robbins Leah E Cowen Alan M Moses
author_facet	Ian S Hsu Bob Strome Emma Lash Nicole Robbins Leah E Cowen Alan M Moses
author_sort	Ian S Hsu
title	A functionally divergent intrinsically disordered region underlying the conservation of stochastic signaling.
title_short	A functionally divergent intrinsically disordered region underlying the conservation of stochastic signaling.
title_full	A functionally divergent intrinsically disordered region underlying the conservation of stochastic signaling.
title_fullStr	A functionally divergent intrinsically disordered region underlying the conservation of stochastic signaling.
title_full_unstemmed	A functionally divergent intrinsically disordered region underlying the conservation of stochastic signaling.
title_sort	functionally divergent intrinsically disordered region underlying the conservation of stochastic signaling.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/fc43d48845f1409795c80b3a2d11b345
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A functionally divergent intrinsically disordered region underlying the conservation of stochastic signaling.

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