SC Connecticut News

Creating zygotes from the genetic material and cytoplasm of two mouse species has led to offspring that differ significantly from their parents, according to a new study. This research may have implications for understanding how new species emerge.

The study was conducted by James McGrath, a clinical geneticist and research scientist at Yale, along with his colleagues. The findings are published posthumously in the journal Science Advances, as McGrath passed away in March. His work explored the possibility that male cytoplasm entering a female's egg during fertilization could lead to new species development.

“Once the sperm enters the egg, the cytoplasm of the male is gone,” explained Tamas Horvath, co-senior author of the study and professor at Yale School of Medicine. “James wanted to know, what if it’s not gone? What if you mix up the gene pool as well as the cytoplasm pool?”

The researchers experimented by creating zygotes with nuclear material and cytoplasm from both male Mus domesticus mice and female Mus spretus mice. Typically, when these species are naturally bred together, they do not produce offspring. However, through what researchers call "true hybridization," offspring were successfully born.

“Mules are the offspring of a horse and a donkey,” noted Horvath. “But the true hybrid mice were much larger than either parental species.” These differences suggest potential mechanisms for evolution.

The resulting true hybrid mice were all male and sterile, prompting further investigation into why this occurs and which components of cytoplasm contribute to these findings.

Throughout his career, McGrath focused on biological mechanisms affecting development and disease. He discovered genomic imprinting in 1984. His latest work indicates that different egg cytoplasm environments can lead to varying offspring development outcomes.

“James was a clinician...and he had an amazing interest in science,” said Horvath. “He was such a remarkable human being and we’re going to make sure we continue his work forward.”

The study received support from institutions including the National Institutes of Health and Yale’s Department of Comparative Medicine. Leyla Sati from Akdeniz University School of Medicine was first author; Luis Varela from Yale School of Medicine was also involved in this research.