Limitations of Serial Cloning in Mammals

5 hours ago

Mammals can be cloned artificially, but serial cloning leads to accumulation of large structural and lethal mutations in DNA.
Serial cloning in mice was performed for 20 years, reaching 58 generations before the birth rate declined and cloning became unsustainable.
Re-cloned mice appeared normal with typical lifespans, but mutations accumulated with each generation, affecting reproductive capacity.
Oocytes from late-generation re-cloned mice could be fertilized, but most embryos degenerated due to genetic anomalies.
A few embryos normalized through meiosis and fertilization, suggesting sexual reproduction is essential for eliminating genetic defects.
Whole-genome sequencing revealed increasing single-nucleotide variants (SNVs) and structural variants (SVs) with each generation.
Mutations became more deleterious after the 25th generation, leading to a decline in cloning success.
Sexual reproduction restored normal litter sizes in offspring of re-cloned mice, demonstrating its role in genetic normalization.
The study supports Muller’s ratchet theory, showing that asexual reproduction leads to mutational meltdown in mammals.
Cloning technology remains limited for practical applications due to genetic instability, reinforcing the necessity of sexual reproduction for species survival.

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