Allele-specific expression and alternative splicing in horse×donkey and cattle×yak hybrids.

Yu Wang,Ming Li,Wei-Huang Chen,Lei Wang,Shan Gao,Guang-Xian Zhou,Yu-Lin Chen,Wei-Dong Deng,Jing-Tao Xu,Ni-Ni Wang,Yu Jiang,Yue Zhao,Wen Wang,Wen-Jing Shen,Jun-Jie Shao

doi:10.24272/j.issn.2095-8137.2019.042

Abstract

Divergence of gene expression and alternative splicing is a crucial driving force in the evolution of species; to date, however the molecular mechanism remains unclear. Hybrids of closely related species provide a suitable model to analyze allele-specific expression (ASE) and allele-specific alternative splicing (ASS). Analysis of ASE and ASS can uncover the differences in cis-regulatory elements between closely related species, while eliminating interference of trans-regulatory elements. Here, we provide a detailed characterization of ASE and ASS from 19 and 10 transcriptome datasets across five tissues from reciprocal-cross hybrids of horse×donkey (mule/hinny) and cattle×yak (dzo), respectively. Results showed that 4.8%–8.7% and 10.8%–16.7% of genes exhibited ASE and ASS, respectively. Notably, lncRNAs and pseudogenes were more likely to show ASE than protein-coding genes. In addition, genes showing ASE and ASS in mule/hinny were found to be involved in the regulation of muscle strength, whereas those of dzo were involved in high-altitude adaptation. In conclusion, our study demonstrated that exploration of genes showing ASE and ASS in hybrids of closely related species is feasible for species evolution research.

Highlights

The accumulation of genetic variations in a genome sequence results in phenotypic diversity and adaptive evolution, with the majority of genetic variations functioning in gene expression regulation (Keane et al, 2011; Kwan et al, 2008)
Among the expressed genes (FPKM≥1), 846 (6.5%), 790 (7.3%), and 905 (6.8%) genes showing allele-specific expression (ASE) were identified in the brain, muscle, and skin tissues of mule/hinny, respectively (Figure 3A, B), whereas 883 (8.7%) and 592 (4.8%) genes showing ASE were identified in the liver and ear of dzo, respectively (Figure 3A, B)
Principal component analysis was conducted based on the allelic expression ratios, which showed that samples were clustered according to tissue type, further indicating tissue specificity in genes showing ASE (Supplementary Figure S3A, B)

Summary

Introduction

The accumulation of genetic variations in a genome sequence results in phenotypic diversity and adaptive evolution, with the majority of genetic variations functioning in gene expression regulation (Keane et al, 2011; Kwan et al, 2008). Identification of changes in the gene expression profiles, including expression levels and alternative splicing, between closely related species It is widely accepted that environmental factors can affect gene expression (Forrest et al, 2014; Prabhakar et al, 2008; Villar et al, 2015), which can hinder comparisons of gene expression profiles between species (Brown et al, 2014). Hybrids of closely related species provide a good model for interspecific comparisons of gene expression pro fi les at the allelic level (Tirosh et al, 2009). The relative expression profiles of two alleles of a heterozygous variant can be assessed by allele-specific expression (ASE) and allelespecific splicing (ASS).

Methods

Results

Conclusion