Course: SAT 170 Introductory Biotechnology

Unit 8 Learning Module

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Animal Cloning

Figure 1

In this next section of the learning module, we will discuss cloning which is a method that is commonly being used for the production of organisms with ideal characteristics by creating genetically identical offspring that also exhibit those characteristics. Figure 1: A descendent of the famous Starbuck cow is an example of creating identical offspring with ideal characteristics.

Now that we have a clear understanding of the processes for molecular and cellular cloning, we can discuss the more complex cloning of multicellular organisms, with a focus on mammalian cloning. Somatic cell nuclear transfer (SCNT) is the primary mechanism used for reproductive cloning. During this procedure, a nucleus is removed from a somatic cell and is then placed into an egg which has had its nucleus previously removed. This egg is said to be enucleated. Recall from unit 2, that the nucleus is the structure of eukaryotes which has the DNA and from unit 7, that a somatic cell is any body cell other than the gametes. Once the egg has acquired the full genome of the somatic cell donor, it can then be placed into a surrogate for development. This is the mechanism that was utilized to generate the famous Dolly the sheep. Recall from unit 1 that Dolly was the first animal that was cloned from the DNA of an adult cell and was born in 1996 from the research of Ian Wilmut and Keith Campbell. Figure 2: This diagram illustrates the mechanism known as somatic cell nuclear transfer (SCNT) which is used for the production of animal clones.

The major hurdle of the SCNT technique comes from the fact that the somatic cell from which the nucleus was obtained is already differentiated, and during the differentiation process, there are significant changes that occur to the DNA. Recall from unit 3, that DNA holds our genetic information is a sequence of adenine (A), thymine (T), cytosine (C) and guanine (G) nucleotides. This genetic material is then passed from one generation to the next. The changes that occur to the DNA, which I was referring to earlier, include the way that DNA is packaged and organized within our cells. For example, DNA molecules wind tightly around a group of proteins known as histones. When bound to these proteins, DNA becomes inaccessible, and thus cannot be expressed. The primary factor that influences how tightly the DNA will be wound around these histone proteins is a process known as histone acetylation. During histone acetylation, a chemical group known as an acetyl is added to the histone proteins. This modification causes the histones to release the DNA, making it accessible for gene expression. A similar process known as DNA methylation, which is the addition of a chemical group known as a methyl to the DNA nucleotides, can also impact the accessibility of DNA for gene expression. Such modifications to gene expression, which do not impact or change the underlying genes, are the focus of epigenetics. It is these epigenetic changes that make cloning difficult as the cell must be reprogrammed to its totipotent state by removing many of these modifications. Figure 3: This diagram highlights the two main types of epigenetic modifications which we discussed in this learning module: histone acetylation and DNA methylation. Notice that when the acetyl group (shown here as the epigenetic factor) is attached to the histone, the histone releases the DNA making the gene (shown in pink) more accessible. Figure 4: The significance of epigenetic modifications, such as DNA methylation, is illustrated here when comparing these two mice clones. Even though they have identical DNA, the mouse on the right had a gene for a kinked tail methylated. This results in the different physical appearance of these mice as the mouse on the left did not receive the epigenetic change and thus expressed the gene for a kinked tail.

A second type of cloning, often referred to as therapeutic cloning, involves the use of embryos as a source of embryonic stem cells. This will be discussed in further detail on the following page.

For much the same reasons as were previously stated for plants, animal clones can be beneficial (i.e. to protect endangered species and to breed organisms with particular desired characteristics).

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Figure 4 - Bradbury J (2003) Human Epigenome Project—Up and Running. PLoS Biol 1(3): e82. doi:10.1371/journal.pbio.0000082
Figure 3