Rondell Melling, PixxlTeufel / Pixabay
Serial cloning of mice has a limit: it began to fail after dozens of generations.
A long-term study recently contradicted the idea that serial cloning could go on indefinitely and even become more efficient over time.
Researchers in Japan have concluded that mammals cannot be cloned generation after generation without serious problems arising: after 57 generations, the effects accumulated in the DNA become too severe, and In the 58th generation, cloned mice no longer survived after birth.
The same team had previously shown that it was possible to clone mice successively over 25 generations with no apparent impact on the animals’ health. At that stage, the results even suggested a gradual improvement in the success rate. But by extending the experiment for another 22 generations, scientists led by Teruhiko Wakayamafrom the University of Yamanashi, in Japan, found a reversal of the trend.
From the 27th generation onwards, Wakayama tells , mutations began to accumulate in the animals’ DNA, while the birth rate decreased. The team initially thought efficiency could continue to improve, but the data showed just the opposite.
Analysis of the complete mouse genome revealed an unusually high number of major structural variants — mutations associated with significant changes in chromosome organization.
The researchers suspect that this damage accumulated since the first cloning, although its negative effects were temporarily masked by a selection process: in each generation, individuals with the greatest capacity to originate viable clones were chosen, which would have allowed the results to be kept stable for some time.
As the generations progressed, the problems became more evident. THE fertility of cloned mice decreased and were also detected changes in the structure of the placenta. Still, when mice from later generations were allowed to reproduce naturally, their descendants showed improved fertility and placentas very similar to those of uncloned mice.
The observation reinforces the importance of sexual reproduction in maintaining biological stability.
The team admits, in the study published in , that they still do not know why clones present around three times more mutations than naturally generated animals. One hypothesis is that the physical cloning process itself damages the cell nucleus, as it has to be extracted with an extremely fine micropipette.
Cloning may continue to be useful, for example, in livestock production with valuable characteristics, as long as preserved cells from the original animal are used instead of successive clones, the team points out.
