Paralogs in the PKA Regulon Traveled Different Evolutionary Routes to Divergent Expression in Budding Yeast

Functional divergence of duplicate genes, or paralogs, is an important driver of novelty in evolution. In the model yeast Saccharomyces cerevisiae, there are 547 paralog gene pairs that survive from an interspecies Whole Genome Hybridization (WGH) that occurred ~100MYA. In this work, we report that ~1/6th (110) of these WGH paralogs pairs (or ohnologs) are differentially expressed with a striking pattern upon Protein Kinase A (PKA) inhibition. One member of each pair in this group has low basal expression that increases upon PKA inhibition, while the other has moderate and unchanging expression. For these genes, expression of orthologs upon PKA inhibition in the non-WGH species Kluyveromyces lactis and for PKA-related stresses in other budding yeasts shows unchanging expression, suggesting that lack of responsiveness to PKA was likely the typical ancestral phenotype prior to duplication. Promoter sequence analysis across related budding yeast species further revealed that the subsequent emergence of PKA-dependence took different evolutionary routes. In some examples, regulation by PKA and differential expression appears to have arisen following the WGH, while in others, regulation by PKA appears to have arisen in one of the two parental lineages prior to the WGH. More broadly, our results illustrate the unique opportunities presented by a WGH event for generating functional divergence by bringing together two parental lineages with separately evolved regulation into one species. We propose that functional divergence of two ohnologs can be facilitated through such regulatory divergence.

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Paralogs in the PKA regulon traveled different evolutionary routes to divergent expression in budding yeast

10.1101/860981 ◽

2019 ◽

Author(s):

Benjamin Murray Heineike ◽

Hana El-Samad

Keyword(s):

Differential Expression ◽

Functional Divergence ◽

Transcriptional Response ◽

Differentially Expressed ◽

Environmental Stress Response ◽

Generating Functional ◽

Promoter Sequences ◽

Gene Pairs ◽

Basal Expression ◽

Paralog Gene

AbstractFunctional divergence of duplicate genes, or paralogs, is an important driver of novelty in evolution. In the model yeast Saccharomyces cerevisiae, there are 547 paralog gene pairs that survive from an interspecies Whole Genome Hybridization (WGH) that occurred ∼100MYA. Many WGH paralogs (or ohnologs) are known to have differential expression during the yeast Environmental Stress Response (ESR), of which Protein Kinase A (PKA) is a major regulator. While investigating the transcriptional response to PKA inhibition in S. cerevisiae, we discovered that approximately 1/6th (91) of all ohnolog pairs were differentially expressed with a striking pattern. One member of each pair tended to have low basal expression that increased upon PKA inhibition, while the other tended to have high but unchanging expression. Examination of PKA inhibition data in the pre-WGH species K. lactis and PKA-related stresses in other budding yeasts indicated that unchanging expression in response to PKA inhibition is likely to be the ancestral phenotype prior to duplication. Analysis of promoter sequences of orthologs of gene pairs that are differentially expressed in S. cerevisiae further revealed that the emergence of PKA-dependence took different evolutionary routes. In some examples, regulation by PKA and differential expression appears to have arisen following the WGH, while in others, regulation by PKA appears to have arisen in one of the two parental lineages prior to the WGH. More broadly, our results illustrate the unique opportunities presented by a WGH event for generating functional divergence by bringing together two parental lineages with separately evolved regulation into one species. We propose that functional divergence of two ohnologs can be facilitated through such regulatory divergence, which can persist even when functional differences are erased by gene conversion.

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Conservation of the Prion Properties of Ure2p through Evolution

Molecular Biology of the Cell ◽

10.1091/mbc.e03-01-0007 ◽

2003 ◽

Vol 14 (8) ◽

pp. 3449-3458 ◽

Cited By ~ 48

Author(s):

Agnès Baudin-Baillieu ◽

Eric Fernandez-Bellot ◽

Fabienne Reine ◽

Eric Coissac ◽

Christophe Cullin

Keyword(s):

Functional Analysis ◽

Candida Albicans ◽

Gene Deletion ◽

Yeast Species ◽

Kluyveromyces Lactis ◽

In Silico Analysis ◽

Functional Domain ◽

Extreme Situation ◽

Homologous Genes ◽

Silico Analysis

The yeast inheritable [URE3] element corresponds to a prion form of the nitrogen catabolism regulator Ure2p. We have isolated several orthologous URE2 genes in different yeast species: Saccharomyces paradoxus, S. uvarum, Kluyveromyces lactis, Candida albicans, and Schizosaccharomyces pombe. We show here by in silico analysis that the GST-like functional domain and the prion domain of the Ure2 proteins have diverged separately, the functional domain being more conserved through the evolution. The more extreme situation is found in the two S. pombe genes, in which the prion domain is absent. The functional analysis demonstrates that all the homologous genes except for the two S. pombe genes are able to complement the URE2 gene deletion in a S. cerevisiae strain. We show that in the two most closely related yeast species to S. cerevisiae, i.e., S. paradoxus and S. uvarum, the prion domains of the proteins have retained the capability to induce [URE3] in a S. cerevisiae strain. However, only the S. uvarum full-length Ure2p is able to behave as a prion. We also show that the prion inactivation mechanisms can be cross-transmitted between the S. cerevisiae and S. uvarum prions.

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Respiration-Dependent Utilization of Sugars in Yeasts: a Determinant Role for Sugar Transporters

Journal of Bacteriology ◽

10.1128/jb.184.2.427-432.2002 ◽

2002 ◽

Vol 184 (2) ◽

pp. 427-432 ◽

Cited By ~ 45

Author(s):

Paola Goffrini ◽

Iliana Ferrero ◽

Claudia Donnini

Keyword(s):

Yeast Species ◽

Kluyveromyces Lactis ◽

Sugar Uptake ◽

Sugar Transporters ◽

High Substrate ◽

Fermentative Growth ◽

Major Bottleneck ◽

Respiratory Conditions

ABSTRACT In many yeast species, including Kluyveromyces lactis, growth on certain sugars (such as galactose, raffinose, and maltose) occurs only under respiratory conditions. If respiration is blocked by inhibitors, mutation, or anaerobiosis, growth does not take place. This apparent dependence on respiration for the utilization of certain sugars has often been suspected to be associated with the mechanism of the sugar uptake step. We hypothesized that in many yeast species, the permease activities for these sugars are not sufficient to ensure the high substrate flow that is necessary for fermentative growth. By introducing additional sugar permease genes, we have obtained K. lactis strains that were capable of growing on galactose and raffinose in the absence of respiration. High dosages of both the permease and maltase genes were indeed necessary for K. lactis cells to grow on maltose in the absence of respiration. These results strongly suggest that the sugar uptake step is the major bottleneck in the fermentative assimilation of certain sugars in K. lactis and probably in many other yeasts.

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The Rap1p-Telomere Complex Does Not Determine the Replicative Capacity of Telomerase-Deficient Yeast

Molecular and Cellular Biology ◽

10.1128/mcb.23.23.8729-8739.2003 ◽

2003 ◽

Vol 23 (23) ◽

pp. 8729-8739 ◽

Cited By ~ 2

Author(s):

Sarit Smolikov ◽

Anat Krauskopf

Keyword(s):

Telomere Length ◽

Replicative Senescence ◽

Budding Yeast ◽

Kluyveromyces Lactis ◽

Dna Binding Protein ◽

Replicative Capacity ◽

Telomeric Dna ◽

Telomeric Repeats ◽

Telomere Lengthening

ABSTRACT Telomeres are nucleoprotein structures that cap the ends of chromosomes and thereby protect their stability and integrity. In the presence of telomerase, the enzyme that synthesizes telomeric repeats, telomere length is controlled primarily by Rap1p, the budding yeast telomeric DNA binding protein which, through its C-terminal domain, nucleates a protein complex that limits telomere lengthening. In the absence of telomerase, telomeres shorten with every cell division, and eventually, cells enter replicative senescence. We have set out to identify the telomeric property that determines the replicative capacity of telomerase-deficient budding yeast. We show that in cells deficient for both telomerase and homologous recombination, replicative capacity is dependent on telomere length but not on the binding of Rap1p to the telomeric repeats. Strikingly, inhibition of Rap1p binding or truncation of the C-terminal tail of Rap1p in Kluyveromyces lactis and deletion of the Rap1p-recruited complex in Saccharomyces cerevisiae lead to a dramatic increase in replicative capacity. The study of the role of telomere binding proteins and telomere length on replicative capacity in yeast may have significant implications for our understanding of cellular senescence in higher organisms.

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Inferring sequence regions under functional divergence in duplicate genes

Bioinformatics ◽

10.1093/bioinformatics/btr635 ◽

2011 ◽

Vol 28 (2) ◽

pp. 176-183 ◽

Cited By ~ 9

Author(s):

Yi-Fei Huang ◽

G. Brian Golding

Keyword(s):

Functional Divergence ◽

Duplicate Genes

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Mutant casein kinase I (Hrr25p/Kti14p) abrogates the G1 cell cycle arrest induced by Kluyveromyces lactis zymocin in budding yeast

Molecular Genetics and Genomics ◽

10.1007/s00438-003-0807-5 ◽

2003 ◽

Vol 269 (2) ◽

pp. 188-196 ◽

Cited By ~ 26

Author(s):

C. Mehlgarten ◽

R. Schaffrath

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Budding Yeast ◽

Kluyveromyces Lactis ◽

Casein Kinase ◽

Casein Kinase I ◽

Cycle Arrest ◽

G1 Cell Cycle Arrest

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Closely related budding yeast species respond to different ecological signals for spore activation

Yeast ◽

10.1002/yea.3538 ◽

2020 ◽

Author(s):

Samuel Plante ◽

Christian R. Landry

Keyword(s):

Yeast Species ◽

Budding Yeast ◽

Spore Activation

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Either of the major H2A genes but not an evolutionarily conserved H2A.F/Z variant of Tetrahymena thermophila can function as the sole H2A gene in the yeast Saccharomyces cerevisiae.

Molecular and Cellular Biology ◽

10.1128/mcb.16.6.2878 ◽

1996 ◽

Vol 16 (6) ◽

pp. 2878-2887 ◽

Cited By ~ 11

Author(s):

X Liu ◽

J Bowen ◽

M A Gorovsky

Keyword(s):

Saccharomyces Cerevisiae ◽

Tetrahymena Thermophila ◽

Yeast Species ◽

Budding Yeast ◽

Yeast Cells ◽

Ciliated Protozoan ◽

Yeast Saccharomyces Cerevisiae ◽

Evolutionarily Conserved ◽

Cold Sensitive ◽

Conserved Epitope

H2A.F/Z histones are conserved variants that diverged from major H2A proteins early in evolution, suggesting they perform an important function distinct from major H2A proteins. Antisera specific for hv1, the H2A.F/Z variant of the ciliated protozoan Tetrahymena thermophila, cross-react with proteins from Saccharomyces cerevisiae. However, no H2A.F/Z variant has been reported in this budding yeast species. We sought to distinguish among three explanations for these observations: (i) that S. cerevisiae has an undiscovered H2A.F/Z variant, (ii) that the major S. cerevisiae H2A proteins are functionally equivalent to H2A.F/Z variants, or (iii) that the conserved epitope is found on a non-H2A molecule. Repeated attempts to clone an S. cerevisiae hv1 homolog only resulted in the cloning of the known H2A genes yHTA1 and yHTA2. To test for functional relatedness, we attempted to rescue strains lacking the yeast H2A genes with either the Tetrahymena major H2A genes (tHTA1 or tHTA2) or the gene (tHTA3) encoding hv1. Although they differ considerably in sequence from the yeast H2A genes, the major Tetrahymena H2A genes can provide the essential functions of H2A in yeast cells, the first such case of trans-species complementation of histone function. The Tetrahymena H2A genes confer a cold-sensitive phenotype. Although expressed at high levels and transported to the nucleus, hv1 cannot replace yeast H2A proteins. Proteins from S. cerevisiae strains lacking yeast H2A genes fail to cross-react with anti-hv1 antibodies. These studies make it likely that S. cerevisiae differs from most other eukaryotes in that it does not have an H2A.F/Z homolog. A hypothesis is presented relating the absence of H2A.F/Z in S. cerevisiae to its function in other organisms.

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