Dosage Compensation and Gene Expression of the X Chromosome in Sheep

• Published in: G3 : genes - genomes - genetics 2019-01, Vol.9 (1), p.305-314
• Main Authors: Duan, Jingyue (Ellie), Flock, Kaleigh, Jue, Nathanial, Zhang, Mingyuan, Jones, Amanda, Seesi, Sahar Al, Mandoiu, Ion, Pillai, Sambhu, Hoffman, Maria, O’Neill, Rachel, Zinn, Steven, Govoni, Kristen, Reed, Sarah, Jiang, Hesheng, Jiang, Zongliang (Carl), Tian, Xiuchun (Cindy)
• Format: Article
• Language: English
• Subjects: Animals; Dosage Compensation, Genetic; Female; Gene Expression Regulation, Developmental - genetics; Genes, X-Linked - genetics; Humans; Investigations; Male; Maternal nutrition; Ohno’s hypothesis; Ovine; Sequence Analysis, RNA; Sheep - genetics; X Chromosome - genetics; X Chromosome Inactivation - genetics; X chromosome upregulation
• ISSN: 2160-1836; 2160-1836
• DOI: 10.1534/g3.118.200815

Abstract Ohno’s hypothesis predicts that the expression of the single X chromosome in males needs compensatory upregulation to balance its dosage with that of the diploid autosomes. Additionally, X chromosome inactivation ensures that quadruple expression of the two X chromosomes is avoided in females. These mechanisms have been actively studied in mice and humans but lag behind in domestic species. Using RNA sequencing data, we analyzed the X chromosome upregulation in sheep fetal tissues from day 135 of gestation under control, over or restricted maternal diets (100%, 140% and 60% of National Research Council Total Digestible Nutrients), and in conceptuses, juvenile, and adult somatic tissues. By computing the mean expression ratio of all X-linked genes to all autosomal genes (X:A), we found that all samples displayed some levels of X chromosome upregulation. The degrees of X upregulation were not significant (P-value = 0.74) between ovine females and males in the same somatic tissues. Brain, however, displayed complete X upregulation. Interestingly, the male and female reproduction-related tissues exhibited divergent X dosage upregulation. Moreover, expression upregulation of the X chromosome in fetal tissues was not affected by maternal diets. Maternal nutrition, however, did change expression levels of several X-linked genes, such as sex determination genes SOX3 and NR0B1. In summary, our results showed that X chromosome upregulation occurred in nearly all sheep somatic tissues analyzed, thus support Ohno’s hypothesis in a new species. However, the levels of upregulation differed by different subgroups of genes such as those that are house-keeping and “dosage-sensitive”.