Dosage Compensation of the X Chromosomes in Bovine Germline, Early Embryos and Somatic Tissues.

Research paper by Jingyue Ellie JE Duan, Wei W Shi, Nathaniel K NK Jue, Zongliang Z Jiang, Lynn L Kuo, Rachel R O'Neill, Eckhard E Wolf, Hong H Dong, Xinbao X Zheng, Jingbo J Chen, Xiuchun Cindy XC Tian

Indexed on: 20 Dec '18Published on: 20 Dec '18Published in: Genome biology and evolution


Dosage compensation of the mammalian X chromosome (X) was proposed by Susumu Ohno as a mechanism wherein the inactivation of one X in females would lead to the doubling the expression of the other. This would resolve the dosage imbalance between eutherian females (XX) vs. male (XY) and between a single active X vs. autosome pairs (A). Expression ratio of X- and A-linked genes has been relatively well-studied in humans and mice, despite controversial results over the existence of up-regulation of X-linked genes. Here we report the first comprehensive test of Ohno's hypothesis in bovine pre-attachment embryos, germline and somatic tissues. Overall an incomplete dosage compensation (0.5<X:A<1) of expressed genes and an excess X dosage compensation (X:A>1) of ubiquitously expressed "dosage-sensitive" genes were seen. No significant differences in X:A ratios were observed between bovine female and male somatic tissues, further supporting Ohno's hypothesis. Interestingly, pre-implantation embryos manifested a unique pattern of X dosage compensation dynamics. Specifically, X dosage decreased after fertilization, indicating that the sperm brings in an inactive X to the matured oocyte. Subsequently, the activation of the bovine embryonic genome enhanced expression of X-linked genes and increased the X dosage. As a result, an excess compensation was exhibited from the 8-cell stage to the compact morula stage. The X dosage peaked at the 16-cell stage and stabilized after the blastocyst stage. Together, our findings confirm Ohno's hypothesis of X dosage compensation in the bovine and extend it by showing incomplete and over-compensation for expressed and "dosage-sensitive" genes, respectively.