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Cited by 386Chromosomal and Genetic VariationsDevelopmental Biology and Gene RegulationGenomics and Phylogenetic Studies

Regulatory divergence in Drosophila revealed by mRNA-seq

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McManus, C. Joel, Coolon, Joseph D., Duff, Michael O., Eipper-Mains, Jodi, Graveley, Brenton R., Wittkopp, Patricia J.·2010·Genome Research
DOI 10.1101/gr.102491.109PMC PMC2877578
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Abstract

The regulation of gene expression is critical for organismal function and is an important source of phenotypic diversity between species. Understanding the genetic and molecular mechanisms responsible for regulatory divergence is therefore expected to provide insight into evolutionary change. Using deep sequencing, we quantified total and allele-specific mRNA expression levels genome-wide in two closely related Drosophila species (D. melanogaster and D. sechellia) and their F(1) hybrids. We show that 78% of expressed genes have divergent expression between species, and that cis- and trans-regulatory divergence affects 51% and 66% of expressed genes, respectively, with 35% of genes showing evidence of both. This is a relatively larger contribution of trans-regulatory divergence than was expected based on prior studies, and may result from the unique demographic history of D. sechellia. Genes with antagonistic cis- and trans-regulatory changes were more likely to be misexpressed in hybrids, consistent with the idea that such regulatory changes contribute to hybrid incompatibilities. In addition, cis-regulatory differences contributed more to divergent expression of genes that showed additive rather than nonadditive inheritance. A correlation between sequence similarity and the conservation of cis-regulatory activity was also observed that appears to be a general feature of regulatory evolution. Finally, we examined regulatory divergence that may have contributed to the evolution of a specific trait--divergent feeding behavior in D. sechellia. Overall, this study illustrates the power of mRNA sequencing for investigating regulatory evolution, provides novel insight into the evolution of gene expression in Drosophila, and reveals general trends that are likely to extend to other species.

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  • Current approaches to allele-specific expression discard allelic multireads that map to both parents and fail to account for reads that are simultaneously genomic and allelic multireads.

    “These methods discard allelic multireads that map to both parents and fail to account for reads that are simultaneously genomic and allelic multireads.”

    From RNA-Seq Alignment to Individualized Genomes Improves Transcript Abundance Estimates in Multiparent Populations (2014) · cites this paper as McManus et al. 2010

    The Results and Discussion say reads that could not be assigned unambiguously to either parent were excluded, supporting part of the claim. But they also say some reads matching both parents were assigned using mate-pair information, so not all such reads were discarded. The Methods discuss reads mapping to multiple genomic locations but do not establish how reads ambiguous in both ways were handled. (LLM, conf=0.85)

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  • After aligning reads, differentiating sites with fewer than 20 overlapping reads were excluded, and binomial exact tests with a false discovery rate threshold of 0.05 were used to test each differentiating site for a statistically significant difference in relative allelic abundance.

    “Therefore, after aligning reads, we excluded differentiating sites with fewer than 20 overlapping reads and used binomial exact tests with a false discovery rate threshold of 0.05 to test each differentiating site for a statistically significant difference in relative allelic abundance [15,27].”

    From Sources of bias in measures of allele-specific expression derived from RNA-seq data aligned to a single reference genome (2013) · cites this paper as [15]

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  • Aligning sequence reads to both parental genomes can eliminate the systematic bias in relative allele-specific expression favoring the reference allele.

    “two alternative strategies for aligning reads have been shown to eliminate the systematic bias in measures of relative ASE favoring the reference allele”

    From Sources of bias in measures of allele-specific expression derived from RNA-seq data aligned to a single reference genome (2013) · cites this paper as [15]

    The Results and Discussion section says that reads from mixed parental and hybrid samples were independently aligned to both parental genomes, supporting the alignment strategy. The paper reports checks on allele-assignment accuracy, but our copy does not show that this strategy eliminated systematic bias favoring a reference allele. (LLM, conf=0.84)

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Authors
McManus, C. J., Coolon, J. D., Duff, M. O., Eipper-Mains, J., Graveley, B. R., & Wittkopp, P. J.
Affiliations
  • University of Connecticut (US)
  • University of Michigan (US)
ORCID
Venue
Genome Research
Publisher
Cold Spring Harbor Laboratory
Published
2010-03-30
Volume
20
Issue
6
Pages
816-825
ISSN
1088-9051 (ISSN-L)
DOI
10.1101/gr.102491.109
PMC
PMC2877578
OpenAlex
W2121547736
Cited by
381
References
51
Citations by year
2026: 16 · 2025: 16 · 2024: 19 · 2023: 18 · 2022: 33 · 2021: 26 · 2020: 34 · 2019: 18 · 2018: 17 · 2017: 16 · 2016: 26 · 2015: 31 · 2014: 27 · 2013: 24 · 2012: 31
Type
posted content
Language
en
Open access
Locations
  • Genome Research (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Alfred P. Sloan Foundation
  • March of Dimes Foundation (5-FY07-181)
  • University of Michigan
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM062516)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
Keywords
regulatory divergence, cis-regulatory divergence, gene expression evolution, Drosophila sechellia, Drosophila melanogaster, interspecific hybrids, hybrid incompatibility, allele-specific expression, additive inheritance, phenotypic diversity
MeSH terms
Animals, Drosophila, Gene Expression Regulation, RNA, Messenger, Species Specificity, Evolution, Molecular, Gene Expression Profiling

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