Allele-specific expression assays using Solexa

Main, Bradley J.; Bickel, Ryan D.; McIntyre, Lauren M.; Graze, Rita M.; Calabrese, Peter; Nuzhdin, Sergey V.

doi:10.1186/1471-2164-10-422

Cited by 40 publications

(48 citation statements)

References 34 publications

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“…In contrast to our interspecific comparisons, background dependency of the relative allelic expression was not observed within species (7,20). This finding suggests that natural selection is promoting compensatory cis-trans evolution.…”

Section: Discussioncontrasting

confidence: 56%

Two types of cis - trans compensation in the evolution of transcriptional regulation

Takahasi

Matsuo

Takano-Shimizu-Kouno

2011

Proc. Natl. Acad. Sci. U.S.A.

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Because distant species often share similar macromolecules, regulatory mutations are often considered responsible for much of their biological differences. Recently, a large portion of regulatory changes has been attributed to cis-regulatory mutations. Here, we examined an alternative possibility that the putative contribution of cis-regulatory changes was, in fact, caused by compensatory action of cis-and trans-regulatory elements. First, we show by stochastic simulations that compensatory cis-trans evolution maintains the binding affinity of a transcription factor at a constant level, thereby spuriously exaggerating the contribution of cis-regulatory mutations to gene expression divergence. This exaggeration was not observed when changes in the binding affinity were compensated by variable transcription factor concentration. Second, using reciprocal introgressions of Drosophila, we show that relative expression of heterozygous alleles from two distinct species often varied significantly between different species backgrounds, indicating the possible action of cis-trans compensation. Taken together, we propose that cis-trans hybrid incompatibilities are accumulating much faster than generally considered. compensatory evolution | trans-regulatory mutation | epistasis | cis-trans interaction | reproductive isolation A first step to understanding the evolution of gene expression is to decompose expression variation into cis-and transregulatory components (1-4). This decomposition can be done by combining an allele-specific expression assay using F 1 hybrids with expression assays in pure species backgrounds (1, 4). From these assays, two kinds of expression differences are determined for a gene: (i) difference between two parental strains and (ii) difference between two alleles in an F 1 hybrid. When the difference between parental strains is entirely due to trans-regulatory changes, we would not expect any difference between the two alleles in the hybrid condition. However, when the difference between parental strains is entirely due to cis-regulatory changes, this difference should be reproduced as an allelic difference in the hybrid. A recent application of this method identified a greater contribution of cis-regulatory changes in inter-than intraspecific comparisons, suggesting that cis-regulatory mutations are fixed more preferentially during evolution than transregulatory mutations (5).In the above decomposition, allelic differences in F 1 hybrids are entirely attributed to cis-regulatory variation under the assumption that trans-regulatory factors should affect both alleles equally. However, some types of cis-trans interactions can violate this assumption by differently affecting the two alleles. For example, by adapting to an evolving cis-regulatory element of the same species, a transcription factor may bind less efficiently with the cis-regulatory element from the distinct species. In the extreme case where the binding between species does not occur at all, an allelic difference in a hybrid would be simil...

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Section: Discussioncontrasting

confidence: 56%

Two types of cis - trans compensation in the evolution of transcriptional regulation

Takahasi

Matsuo

Takano-Shimizu-Kouno

2011

Proc. Natl. Acad. Sci. U.S.A.

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“…For genomic analysis of the evolution of gene expression, cis-acting differences in a heterozygote diploid can be mapped at high resolution (20)(21)(22), but to date, methods for this purpose have required custom microarray tools. The RNA-seq platform we pioneer here enables study of cis-acting variation in expression in any organism and any strain (23)(24)(25). Likewise, we have demonstrated the power of extending the classical sequence-based McDonald-Kreitman test for selection to pathways, an approach that has increasing utility with the advent of population genomic sequencing data (5)(6)(7)(8)32).…”

Section: Discussionmentioning

confidence: 99%

“…Detecting expression variation within the hybrid requires techniques that recognize the alleles encoded by each ortholog in each species. For this purpose, we measured allele-specific expression with Illumina short-read sequencing (RNA-seq) (23)(24)(25). We mated the W303 strain of S. cerevisiae and the CBS 4001 isolate of S. bayanus to form a hybrid diploid and isolated RNA from two independent cultures of this strain as biological replicates.…”

Section: Resultsmentioning

confidence: 99%

Polygenic and directional regulatory evolution across pathways in Saccharomyces

Bullard

Mostovoy

Dudoit

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

142

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The search to understand how genomes innovate in response to selection dominates the field of evolutionary biology. Powerful molecular evolution approaches have been developed to test individual loci for signatures of selection. In many cases, however, an organism's response to changes in selective pressure may be mediated by multiple genes, whose products function together in a cellular process or pathway. Here we assess the prevalence of polygenic evolution in pathways in the yeasts Saccharomyces cerevisiae and S. bayanus. We first established short-read sequencing methods to detect cis-regulatory variation in a diploid hybrid between the species. We then tested for the scenario in which selective pressure in one species to increase or decrease the activity of a pathway has driven the accumulation of cis-regulatory variants that act in the same direction on gene expression. Application of this test revealed a variety of yeast pathways with evidence for directional regulatory evolution. In parallel, we also used population genomic sequencing data to compare protein and cis-regulatory variation within and between species. We identified pathways with evidence for divergence within S. cerevisiae, and we detected signatures of positive selection between S. cerevisiae and S. bayanus. Our results point to polygenic, pathway-level change as a common evolutionary mechanism among yeasts. We suggest that pathway analyses, including our test for directional regulatory evolution, will prove to be a relevant and powerful strategy in many evolutionary genomic applications.A main challenge of evolutionary biology is to understand the influence of selection on genetic variation within and between species. Classically, molecular evolution methods have targeted individual genes or loci for tests of selection. Their successes have uncovered both protein-coding and regulatory variants with signatures of non-neutral evolution (1-3). However, decades of quantitative genetic mapping studies indicate that in most cases, variation in phenotype between individuals is the result of multiple sequence changes at unlinked loci (4). The genetic response to changes in selective pressure is likely to follow the same pattern, but, to date, methods for identifying cases of polygenic evolution have been at a premium.Some of the strongest evidence for polygenic adaptation has emerged from the study of protein-coding variants between phylogenetic lineages. Signatures of positive selection can be detected in the protein-coding sequences of groups of genes of related function (5-8), suggestive of a coherent series of genetic changes accumulated by a population in response to selection. Additionally, genetic variation in gene expression represents a rich data source for signatures of selection, both positive (9, 10) and purifying (11,12), although the mechanisms that govern regulatory evolution are not fully understood. Regulatory variants can act in cis, to impact the expression of a neighboring gene, or in trans, targeting the expression of genes el...

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“…The second row indicates the expected expression patterns of (c) cis mutations and (d) trans mutations in the offspring genomes. (Main et al 2009) and A. thaliana (Zhang & Borevitz 2009) and between individuals from closely related species in Drosophila (Ranz et al 2004;Wittkopp et al 2004;Landry et al 2005) and Saccharomyces (Tirosh et al 2009). …”

Section: Allele-specific Assays For Measuring Cis and Trans Expressiomentioning

confidence: 99%

The genetic basis of evolutionary change in gene expression levels

Emerson

2010

Phil. Trans. R. Soc. B

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The regulation of gene expression is an important determinant of organismal phenotype and evolution. However, the widespread recognition of this fact occurred long after the synthesis of evolution and genetics. Here, we give a brief sketch of thoughts regarding gene regulation in the history of evolution and genetics. We then review the development of genome-wide studies of gene regulatory variation in the context of the location and mode of action of the causative genetic changes. In particular, we review mapping of the genetic basis of expression variation through expression quantitative trait locus studies and measuring the cis/trans component of expression variation in allele-specific expression studies. We conclude by proposing a systematic integration of ideas that combines global mapping studies, cis/trans tests and modern population genetics methodologies, in order to directly estimate the forces acting on regulatory variation within and between species.

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Allele-specific expression assays using Solexa

Cited by 40 publications

References 34 publications

Two types of cis - trans compensation in the evolution of transcriptional regulation

Two types of cis - trans compensation in the evolution of transcriptional regulation

Polygenic and directional regulatory evolution across pathways in Saccharomyces

The genetic basis of evolutionary change in gene expression levels

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