Investigating cross-species hybrid incompatibilities
The egg cytoplasm of a given species can only support normal development promoted by its own genome or nucleus. As a result, when the nucleus of one species is transplanted into the enucleated egg of a distantly related species, development arrests at an early stage. We have developed a simplified system using two frog species that allowed us to find some of the principles that underlie this cross-species incompatibility.
HFSP Long-Term Fellow Patrick Narbonne and colleagues
When two populations are reproductively isolated for several million years, over the course of evolution they normally accumulate many small differences in their characters, such that individuals from one population become visibly distinct from those of the second population, giving rise to two separate species. This occurs because many mutations accumulated within the genomes that are embedded within the nuclei of these two species, affecting not only how the animals look, or their phenotypes, but also importantly how eggs are prepared inside their germ line, and how embryos develop to give rise to the newly evolved, distinct characters of the two species. Because the initial steps of embryonic development are entirely under the control of the egg cytoplasm, the egg cytoplasm will try to initiate the development that would normally be promoted by its own species’ genome, even if it receives one that’s coming from another species, which would require a distinct set of priming steps. Thus, because of these accumulated differences between species, the egg cytoplasm of a given species can only support the normal development that is promoted by its own species’ genome.
Figure:A male Xenopus tropicalis frog is investigating whether it could make use of eggs laid by its giant, distantly related sister Xenopus laevis.
We have tried to understand in greater detail what types of problem occur in a special kind of cross-species hybrid embryo, which are formed by the combination of the egg cytoplasm from one species, and the nucleus of another species. These are called nucleo-cytoplasmic hybrid embryos or cybrids and do not normally occur in nature, but they can be generated experimentally, such as with the technique of nuclear transfer. To study this phenomenon, we developed a simplified system that takes advantage of two evolutionarily distant frog species (Xenopus laevis and Xenopus tropicalis).
We found that cybrid frog embryos with X. laevis cytoplasm and X. tropicalis nuclei are always defective in an important process that is necessary to generate the cell movements that shape the embryo during development. The large size of these amphibian embryos facilitating our task, we could dissect out parts of cybrid embryos, or recombine them with parts taken from normal embryos, and observe their behaviour in culture to identify at exactly which step the defect occurs. These embryonic cell movements normally occur in response to a morphogenetic signal and cybrid explants were largely insensitive to this signal. Interestingly, one of the key molecules that is responsible for responding to this signal exists at different concentrations in the embryos of the two species, while in cybrid embryos the concentration was according to the cytoplasmic species, thereby inappropriate for signalling to the nuclei that it now had. Thus we reasoned that differences in the concentration of key signalling molecules between the two species could lead to developmental defects in cybrid embryos. We further show that the developmental defects of cybrid explants and embryos can be partly improved by treatments that specifically compensate for the identified signalling problems. These concepts are important as they help to understand how the nucleus and the cytoplasm interact during early development, and what kind of reproductive barriers arise between species during evolution.
Reference
Deficient Induction Response in a Xenopus Nucleocytoplasmic Hybrid. Narbonne P, Simpson DE, Gurdon JB (2011) PLoS Biol 9(11): e1001197. (doi:10.1371/journal.pbio.1001197)
Other references
Breaking the Hybrid–Species Barrier. Shields R (2011) PLoS Biol 9(11): e1001201. (doi:10.1371/journal.pbio.1001201)
