Over 20 Years, One Mouse Was Cloned for 58 Generations — Until the Line Collapsed
Cloning can recreate an animal almost exactly, at least initially. But with each generation, small genetic changes begin to accumulate.
Over the course of a 20-year experiment, researchers repeatedly cloned mice from a single original donor, producing more than 1,200 animals over 58 generations. The mice appeared healthy and lived a normal lifespan. But with each round of cloning, mutations quietly accumulated in their DNA, eventually reducing success rates and halting the process. Over the past few generations, cloning has been successful less than 1% of the time. The results, published in Natureshow that while cloning can nurture individuals, it may not nurture a species.
The results point to a fundamental limitation. “Mammals rely on sexual rather than asexual reproduction to eliminate genetic abnormalities caused by clonal reproduction,” the authors state in the study.
A 20-year animal cloning experience
The experiment began in 2005, using cells from a single female mouse. The researchers used somatic cell nuclear transfer (the same technique used for Dolly the Sheep) to produce each new generation. In this process, the nucleus of a body cell is inserted into an egg cell to create a new individual. Cells from one cloned mouse were then used to produce the next one, repeating the process over nearly two decades.
At first, the results were promising. Cloning success rates improved over the first few generations, peaking in the mid-20s. The mice appeared normal, with typical body weight and a lifespan of about two years, comparable to naturally raised mice.
After 25 generations, success rates began to decline. By the 57th generation, cloning worked less than 1% of the time. The 58th generation was the last since none survived more than a day after birth.
Learn more: Transforming skin cells into viable human eggs could be an important step in treating infertility
Quietly constructed mutations
This decline was not due to visible health problems in the mice themselves. Instead, the problem was hidden in their DNA.
Whole genome sequencing revealed that each generation accumulated new mutations, approximately 70 single-letter DNA changes and more than one structural mutation per generation. Over time, these changes added up to thousands of genetic alterations.
Over subsequent generations, these changes included dozens of mutations that could disrupt gene function, as well as larger chromosomal alterations. Overall, mutation rates in cloned mice were about three times higher than in naturally breeding mice, accelerating the accumulation of genetic damage over time.
Some mutations had little effect. Others were more disruptive, including large-scale structural changes such as chromosomal rearrangements and deletions that could interfere with normal development.
At the start of the experiment, harmful mutations may have been filtered out, thereby improving cloning success. But over the generations, this balance has changed. The number of damaging mutations increased, eventually overwhelming the system.
Unlike sexual reproduction, cloning does not mix genes or dilute or remove harmful mutations. Instead, each generation inherits all of the accumulated changes, as well as any new changes that may arise.
Why sex still matters
Even toward the end of the experiment, many of the cloned mice remained healthy. But problems arose when it came to reproduction.
Cells from later generation clones increasingly failed to support early development. In testing, many embryos failed before development could progress, revealing that degradation begins long before birth.
However, when these same mice reproduced sexually with normal males, some offspring developed successfully. The process of meiosis and fertilization appears to allow the formation of viable embryos.
This contrast highlights the key role of sexual reproduction: not only creating variation, but actively preventing the accumulation of harmful mutations over time.
The results align with an evolutionary idea known as Muller’s ratchet – the concept that in asexual populations, mutations accumulate irreversibly until they become unsustainable.
In this case, the process took place over decades. Cloning alone pushed mice toward a genetic tipping point, a point where sexual reproduction could help delay or buffer genetic damage, but not avoid it indefinitely.
Learn more: The world’s most planted wine grape still carries signals from the 1600s
Article sources
Our Discovermagazine.com editors use peer-reviewed research and high-quality sources for our articles, and our editors review the articles for scientific accuracy and editorial standards. See the sources used below for this article:
