Somatic Cell Nuclear Transfer: the Conservation Genomic Solution You Haven’t Heard Of

One of biggest concerns for conservation geneticists is the effect of inbreeding on the long-term viability of an endangered species. Following a decline in population size, the risk of inbreeding increases partly because there are fewer individuals to mate with thus any two individuals are more likely to be related. Over several generations, this risk of mating between individuals that share recent ancestors increases. The problem with small populations and inbreeding is that deleterious mutations accumulate in the population. A famous example of an inbred population with deleterious mutations is the Florida panther; from slow sperm (it’s hard to make kittens if the sperm don’t have enough energy to swim to the egg) to increased disease susceptibility, the alleles in this population resulted in few births and early mortality, problems that kept the population size low.

For species with small population sizes, managed captive breeding is one solution to increase population size before reintroducing individuals into the wild. Captive breeding efforts often use genetic data and pedigrees to breed the least related individuals and maintain the greatest amount of genetic diversity. There are a number of challenges to captive breeding, including that there are only so many individuals to breed at any one time. This limits both the number of matings that can be tried, and the genetic diversity within the captive pool (remember, we’re often trying to maintain or increase genetic diversity). But conservation genomics offers a potential solution: somatic cell nuclear transfer, better known as cloning.

Somatic cell nuclear transfer (SCNT) was the technique used to produce Dolly the sheep. The idea is to remove the nucleus from one somatic (2n, diploid) and one egg (1n, haploid) cell from two different females, then transfer the diploid nucleus into the de-nucleated egg. After some tissue culture magic, the embryo is implanted into a surrogate female for the remainder of embryonic development.

Somatic Cell Nuclear Transfer (aka- Cloning) The nucleus of the diploid somatic cell is transferred into the de-nucleated egg cell, before implantation of the zygote into a surrogate.
Somatic Cell Nuclear Transfer (aka- Cloning)
The nucleus of the diploid somatic cell is transferred into the de-nucleated egg cell, before implantation of the zygote into a surrogate.

This process is slightly majorly tweaked for conservation; specifically, instead of using the same species for both the somatic and egg cell donations, the somatic cell comes from an endangered species and the egg comes from an abundant (often domesticated) species. Then the domestic species is used as the surrogate mother for implantation of the embryo. Thus this process is often referred to as interspecies cloning. Interspecies cloning has been tried on bantengs (Bos javanicus, an endangered bovine from Southeast Asia), black-footed ferrets (Mustela nigripes), and bighorn sheep (Ovis canadensis). Given the variety of domestics (cows, horses, pigs, goats, sheep, dogs, cats, ferrets, and camels), this opens the door for a number of endangered species within the same genera to be candidates for interspecies cloning.

Interspecies Cloning Differing from "regular" cloning due to the use of two different species, where the diploid somatic cell comes from an endangered species and the de-nucleated egg cell and surrogate are from a domesticated species.
Interspecies Cloning
Differing from “regular” cloning due to the use of two different species, where the diploid somatic cell comes from an endangered species and the de-nucleated egg cell and surrogate are from a domesticated species.

Challenges
Death. Mortality for SCNT is high across all process stages. I glossed over the part that the somatic cell from the endangered species can be any cell type, and the first step in SCNT is to de-differentiate the cell. This means if you take a skin cell, the cell must be reprogramed to express embryonic genes, not just express the genes to make skin. If the reprogramming is successful (and it’s not ~30% of the time), the cell must then proceed through all the steps of early embryogenesis, no easy task which is why ~70% of reprogramed cells fail at this step. After all of that reprograming the embryo must have normal development, and here too there is a high rate of embryo death. A final challenge with cloned animals, is that animals die younger; however, if they have contributed to the gene pool for the next generation, then the clone would still be considered a conservation success.

The challenges of SCNT and extra challenges of interspecies cloning are also opportunities to learn a lot about embryology, mito-nuclear conflict (because the cloned animal will have the mitochondrial genome from the donor cell), cellular programing, cellular aging, and the role of epigenetics in imprinting and development.

Of course, none of the biological challenges address issues of allocating conservation funding, public perception, or ethical issues associated with cloning.

Animal pictures from PhyloPic.

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