Introns control stochastic allele expression bias

Abstract

Monoallelic expression (MAE) or extreme allele bias can account for incomplete penetrance, missing heritability and non-Mendelian diseases. In cancer, MAE is associated with shorter patient survival times and higher tumor grade. Prior studies showed that stochastic MAE is caused by stochastic epigenetic silencing, in a gene and tissue-specific manner. Here, we used C. elegans to study stochastic MAE in vivo. We found allele bias/MAE to be widespread within C. elegans tissues, presenting as a continuum from fully biallelic to MAE. We discovered that the presence of introns within alleles robustly decreases MAE. We determined that introns control MAE at distinct loci, in distinct cell types, with distinct promoters, and within distinct coding sequences, using a 5’-intron position-dependent mechanism. Bioinformatic analysis showed human intronless genes are significantly enriched for MAE. Our experimental evidence demonstrates a role for introns in regulating MAE, possibly explaining why some mutations within introns result in disease.

Transgressive and parental dominant gene expression and cytosine methylation during seed development in Brassica napus hybrids

“…The extent of these features in an allopolyploid model crop like B. napus also have potential implications in other polyploid crops where heterosis still remains to be exploited, such as wheat and potatoes (Steeg et al 2022 ). Patterns of expression and methylation dominance levels could also contribute a new level of understand regarding allele-specific gene expression (Fan et al 2020 ; Sands et al 2021 ), isoform expression (Vitting-Seerup and Sandelin 2019 ; Yao et al 2020 ; Golicz et al 2021 ), gene fusion and dosage (Mahmoud et al 2019 ; Serin Harmanci et al 2020 ; Bird et al 2021b ) as well as non-germline omics variations among F 1 plants and populations (Higgins et al 2018 ; Cortijo et al 2019 ; Orantes-Bonilla et al 2022 ; Quezada-Martinez et al 2022 ). Their role in heterotic gene expression patterns is ultimately also of interest for transcriptome-based genomic selection or hybrid performance prediction (e.g.…”

Transgressive and parental dominant gene expression and cytosine methylation during seed development inBrassica napushybrids

“…Expression and methylation dominance levels are a fast way of interpretating -omics data, and to our knowledge, the present study is the first one to analyze expression and methylation dominance level patterns in hybrids derived from two Brassica napus parents. Recent advances in allele specific expression (Fan et al, 2020;Sands et al, 2021), isoform expression (Vitting-Seerup and Sandelin, 2019;Yao et al, 2020;Golicz et al, 2021), gene fusion and dosage (Mahmoud et al, 2019;Serin Harmanci et al, 2020;Bird et al, 2021b) as well as non-germline -omics variations among F1 plants and populations (Higgins et al, 2018;Cortijo et al, 2019;Orantes-Bonilla et al, 2022;Quezada-Martinez et al, 2022) would prove useful in improving the resolution of ELD and MLD analyses. Furthermore, multi-omics features have been employed in genomic selection in plants; hence, defining the role from each -omic feature per stage could be used to enhance expression and phenotype prediction modelling in B.napus (Seifert et al, 2018;Zrimec et al, 2020;Cheng et al, 2021;H.…”

“…The extent of these features in an allopolyploid model crop like B. napus also have potential implications in other polyploid crops where heterosis still remains to be exploited, such as wheat and potatoes (Steeg et al, 2022). Patterns of expression and methylation dominance levels could also contribute a new level of understand regarding allele-specific gene expression (Fan et al, 2020; Sands et al, 2021), isoform expression (Vitting-Seerup and Sandelin, 2019; Yao et al, 2020; Golicz et al, 2021), gene fusion and dosage (Mahmoud et al, 2019; Serin Harmanci et al, 2020; Bird et al, 2021b) as well as non-germline omics variations among F1 plants and populations (Higgins et al, 2018; Cortijo et al, 2019; Orantes-Bonilla et al, 2022; Quezada-Martinez et al, 2022). Their role in heterotic gene expression patterns is ultimately also of interest for transcriptome-based genomic selection or hybrid performance prediction (e.g.…”

“…The extent of these features in an allopolyploid model crop like B. napus also have potential implications in other polyploid crops where heterosis still remains to be exploited, such as wheat and potatoes(Steeg et al, 2022). Patterns of expression and methylation dominance levels could also contribute a new level of understand regarding allelespecific gene expression(Fan et al, 2020;Sands et al, 2021), isoform expression (Vitting-…”

ClockstaRX: testing molecular clock hypotheses with genomic data

“…Null expectations of various degrees of selection across clusters or data types could be tested using simulations and used to assess the crucial role of introns in gene regulation (Chorev and Carmel 2012;Rose 2019). Specifically, the high evolutionary rates of introns might be driven by the fast-evolving nature of adaptive gene expression (Ghalambor et al 2015;Sands et al 2021), rather than simply reflecting the underlying rates of neutral mutation. The support for a second principal component in these data (explaining 13.9% of the variance) suggests that other processes have driven variation in evolutionary rates.…”