CA cloning

We continue the experiment of the previous chapter . The CA on the left is the wild type, while the mutant CA was injured at t =2.  We  remove the first two rows (states) and a new picture emerges. It seems as if both CA start from the same initial  state (a gray square). The mutant lags by three time units. Why do they differ?   Since their  age distributions  differ. The age of the wild type zygote is zero, while the age of the mutant square at t = 3, is greater than zero.

Let's distinguish  between two cell types: A zygote whose age = 0, and a somatic cell whose age > 0. The two gray squares (genes) may look alike yet have different ages. A similar zygote-like somatic cell appears in the left tail at t = 40. The inset is similar to the above image, nevertheless the cell lacks the capacity to form two tails like a real zygote, since its  age > 0.  In the next CA the right tail was cut off. In the third CA the age of the cell at t = 40 was set to zero, and it grew a double tail. Compare with the wild type CA.


The experiment illustrates a major stumbling block of cell cloning. The procedure seems simple and straight forward. You remove a nucleus from an egg, and replace it with another one. You switch two DNA molecules, or blue prints. And yet this simple explanation is deceiving, since each blue print has a different (biological) age. Imagine that the above CA zygote was replaced with the somatic cell of t = 40. It would not  grow two tails. Only after eliminating its age structure and setting it to zero, it regains the power of a zygote to form two tails. 

When Dolly was cloned,  the nucleus of an  egg was replaced with  a nucleus of the skin. Dolly is not so healthy because its genetic material is old. Most cloned eggs  die. Other develop malformations, because they received old nuclei.


As  embryo develops, cells become committed to different lineages because gene-expression programs change as cells differentiate. This commitment is represented in the CA  by state, and age. Each new state and its age structure  are equivalent to lineage commitment. Morphologically, the nuclei in some cloned embryos resemble those of the somatic cells that were used for cloning. The cloned cells retained their (advanced) biological age of the donor nucleus, like in our previous experiment.

Another  obstacle to cloning is the egg  cytoplasm, which is regarded as an inert container for carrying the fused nucleus. Yet  the cytoplasm is very active. It carries mitochondria with  their own DNA, which it inherited from the mother. Its protein will determine the axis of symmetry of the developing fetus, and the future site of its head. Other cytoplasmic factors control  nuclear genes by a process called imprinting. All these factors were inherited form the mother! 

Monozygotic twins

With all these obstacles one wonders  whether  cloning  is really feasible? The answer is provided by Nature, when a fertilized egg divides into two identical twins. Both get the same genes, and cytoplasmic factors. They are the best clones one can hope for.  Are they really identical? Or simply similar, like our two CA depicted above?

Further reading:
Cloning fallacy
Beware of the Gene
Iatrogenic Medicine


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