Genome-wide association mapping of transcriptome variation in Mimulus guttatus indicates differing patterns of selection on cis- versus trans-acting mutations

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 (AFS) 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 super-abundance 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 co-expressed 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.

Supergene potential of a selfish centromere

“…To examine patterns of gene expression across MDL11 haplotypes, we used publicly available RNASeq reads from two datasets. Specifically, we analysed (1) young bud transcriptomes from an eGWAS study of inbred lines from the IM population of M. guttatus that were either D or D − homozygotes ([45] SRA project number PRJNA736440) and (2) carpel and stamen transcriptomes collected from three replicates each of a M. guttatus DD individual (IM62) and an M. nasutus dd individual ([44] Biosample project # SAMN13979871- SAMN13979871).…”

“…For the intraspecific datasets, RNASeq data from 151 IM lines ( D or D − homozygotes) were initially treated as described in [45]. MDL11 haplotype calls followed [54] and five MDL11 heterozygotes (125, 294, 1133, Z368 and Z99) were dropped.…”

“…MDL11 haplotype calls followed [54] and five MDL11 heterozygotes (125, 294, 1133, Z368 and Z99) were dropped. Mapping, variant calling, and filtering are described in detail in [45]. In brief, reads were trimmed with bbuk from BBTools 38.86 () and aligned to the M. guttatus v2 reference genome () with STAR 2.5.0a [55].…”

“…Thus, these samples capture key reproductive stages when we might also expect differences in expression relevant to drive and its costs. Second, we used a large eGWAS dataset ( N = 151 lines; [45]) to investigate patterns of expression divergence between D and D − haplotypes within IM. This large dataset from young floral buds (which are a mix of tissues) do not precisely capture tissue-specific divergence in gene expression, but is ideally suited for characterizing the direct consequences of D 's sweep for constitutive expression variation at the population scale.…”

“…This large dataset from young floral buds (which are a mix of tissues) do not precisely capture tissue-specific divergence in gene expression, but is ideally suited for characterizing the direct consequences of D 's sweep for constitutive expression variation at the population scale. Because there is little evidence of trans- effects of common alleles on gene expression on other chromosomes [45], we focus on loci within MDL11 and flanking regions. While linkage disequilibrium within MDL11 makes it impossible to rule out (or in) any gene in the interval as a contributor to drive and costs, significant shifts in expression (particularly those consistent across datasets) may help identify functional candidates important in the biology of this selfish supergene.…”