Journal
GENETICS
Volume 220, Issue 1, Pages -Publisher
GENETICS SOCIETY AMERICA
DOI: 10.1093/genetics/iyab189
Keywords
eGWAS; coexpression modules; selection; floral traits; transcriptome; regulatory; monkeyflower
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Funding
- National Science Foundation [PRFB IOS-1907061]
- Center for Research Computing at the University of Kansas
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The study of the floral bud transcriptome in Mimulus guttatus revealed a difference in allele frequency spectrum between cis-acting and trans-acting mutations, with the latter influenced by gene expression modules and predicting allele frequency and plant traits.
We measured the floral bud transcriptome of 151 fully sequenced lines of Mimulus guttatus from one natural population. Thousands of single nucleotide polymorphisms (SNPs) are implicated as transcription regulators, but there is a striking difference in the allele frequency spectrum of cis-acting and trans-acting mutations. Cis-SNPs have intermediate frequencies (consistent with balancing selection) while trans-SNPs exhibit a rare-alleles model (consistent with purifying selection). This pattern only becomes clear when transcript variation is normalized on a gene-to-gene basis. If a global normalization is applied, as is typically in RNAseq experiments, asymmetric transcript distributions combined with rarity disequilibrium produce a superabundance of false positives for trans-acting SNPs. To explore the cause of purifying selection on trans-acting mutations, we identified gene expression modules as sets of coexpressed genes. The extent to which trans-acting mutations influence modules is a strong predictor of allele frequency. Mutations altering expression of genes with high connectedness (those that are highly predictive of the representative module expression value) have the lowest allele frequency. The expression modules can also predict whole-plant traits such as flower size. We find that a substantial portion of the genetic (co)variance among traits can be described as an emergent property of genetic effects on expression modules.
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