Dolly's Diverse Heritage

Dolly and other cloned sheep may look like exact replicas, but they aren't. A study in this week's Nature Genetics shows that the DNA in Dolly's mitochondria--the cells' power plants--is not from her genetic mother, but from her second "parent," the sheep that donated the "empty" egg cell. The finding may be important for breeders who want to use cloning to create transgenic animals, because mitochondria may be home to some crucial genes.

Dolly was created using nuclear transfer, a technique in which an intact donor cell is fused with an egg whose nucleus had been removed. In the process, the cytoplasm (the cellular soup in which mitochondria and other cellular organelles float) of both cells is mixed, so one might expect the resulting embryos to inherit mitochondria from both. However, during normal fertilization, when an egg and a sperm fuse, the sperm's mitochondria are destroyed, as the embryo inherits only its mother's mitochondria. Scientists think this happens because having two sets of mitochondria might somehow disturb cellular physiology. "Natural selection works pretty hard to eliminate this," says James Cummins, a biochemist at Murdoch University in Perth, Australia.

Molecular biologist Eric Schon and his colleagues at Columbia University in New York, in collaboration with Dolly's creators at the Roslin Institute in Edinburgh, Scotland, wondered whether during cloning a donor cell's mitochondria, like those of sperm, are taken out of the picture. Schon's team compared a highly variable region of the mitochondrial DNA from cells of Dolly's genetic mother and from the breed of sheep that provided the surrogate egg. They found four differences that together gave a reliable genetic fingerprint for each individual. Next they tested mitochondrial DNA from Dolly and nine other cloned sheep and found that "in all of them the mitochondria came just from one source," says Schon--the recipient egg. The mitochondria from the donor cells had disappeared, apparently having suffered the same fate as sperm mitochondria.

"This is a very interesting finding," says reproductive biologist James Robl of the University of Massachusetts, Amherst. Although mitochondria encode a mere 37 genes, some may be important for certain traits desired in superior livestock. For example, nuclear transfer experiments in dairy cows, says Robl, suggest "there is a significant difference in milk production that could be attributed to the [recipient] cytoplasm."