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Abstract 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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Quantifying the Evolution of SNPs That Affect RNA Secondary Structure in Arabidopsis thaliana Genes
Abstract Single-stranded RNA molecules can form intramolecular bonds between nucleotides to create secondary structures. These structures can have phenotypic effects, meaning mutations that alter secondary structure may be subject to natural selection. Here, we examined the population genetics of these mutations within Arabidopsis thaliana genes. We began by identifying derived SNPs with the potential to alter secondary structures within coding regions, using a combination of computational prediction and empirical data analysis. We identified 8,469 such polymorphisms, representing a small portion (∼0.024%) of sites within transcribed genes. We examined nucleotide diversity and allele frequencies of these “pair-changing mutations” (pcM) in 1,001 A. thaliana genomes. The pcM SNPs at synonymous sites had a 13.4% reduction in nucleotide diversity relative to non-pcM SNPs at synonymous sites and were found at lower allele frequencies. We used demographic modeling to estimate selection coefficients, finding selection against pcMs in 5′ and 3′ untranslated regions. Previous work has shown that some pcMs affect gene expression in a temperature-dependent matter. We explored associations on a genome-wide scale, finding that pcMs existed at higher population frequencies in colder environments, but so did non-PCM alleles. Derived pcM mutations had a small but significant relationship with gene expression; transcript abundance for pcM-containing alleles had an average reduction in expression of ∼4% relative to alleles with conserved ancestral secondary structure. Overall, we document selection against derived pcMs in untranslated regions but find limited evidence for selection against derived pcMs at synonymous sites.
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- Award ID(s):
- 2414478
- PAR ID:
- 10609985
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- Molecular Biology and Evolution
- Volume:
- 42
- Issue:
- 6
- ISSN:
- 0737-4038
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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