Affiliation:
1. Department of Chemical Biology, School of Life Sciences, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, 518055 Shenzhen, China
Abstract
Hybrid incompatibility as a kind of reproductive isolation contributes to speciation. The nucleocytoplasmic incompatibility between
Xenopus tropicalis
eggs and
Xenopus laevis
sperm (
t
e
×
l
s
) leads to specific loss of paternal chromosomes 3L and 4L. The hybrids die before gastrulation, of which the lethal causes remain largely unclear. Here, we show that the activation of the tumor suppressor protein P53 at late blastula stage contributes to this early lethality. We find that in stage 9 embryos, P53-binding motif is the most enriched one in the up-regulated Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) peaks between
t
e
×
l
s
and wild-type
X. tropicalis
controls, which correlates with an abrupt stabilization of P53 protein in
t
e
×
l
s
hybrids at stage 9. Inhibition of P53 activity via either
tp53
knockout or overexpression of a dominant-negative P53 mutant or Murine double minute 2 proto-oncogene (Mdm2), a negative regulator of P53, by mRNA injection can rescue the
t
e
×
l
s
early lethality. Our results suggest a causal function of P53 on hybrid lethality prior to gastrulation.
Funder
Shenzhen Municipal Science and Technology Innovation Council | Shenzhen Science and Technology Innovation Program
Publisher
Proceedings of the National Academy of Sciences