Cytological and biochemical correlation of late X-chromosome replication and gene inactivation in the mule.

The correlation between late X-chromosome replication and the quantitation of different X-linked glucose-6-phosphate dehydrogenase electrophoretic forms was studied in a natural hybrid, the female mule. In all four animals examined, a significant deviation from the expected 1: 1 ratio of random X-chromosome inactivation was observed, with the donkey X-chromosome the more frequently late-replicating one. The relative amounts of horse and donkey enzymes activities in lysates of mule skin fibroblasts and in peripheral blood were in agreement with this finding: the donkey enzyme was the minor component. Although random expression of the enzymes from the two parent species was not observed, sampling, selection, or adaptation may actually be responsible for the apparent "preferential inactivation". These studies support the hypothesis that late DNA replication indicates genetic inactivation.