Question by Makayla Estill, answers by Theresa Mecklenborg
Hi there! My name is Makayla Estill and i am a high schooler in Oregon doing a project about cloning. I have a questions for you:) if you could answer it, it would be very much appreciated!
Question: It seems to be that throughout all the cloning experiments, a high majority of the organisms cloned have died due to/developed mutations and/or other handicaps. Why exactly is this since there is nothing wrong with the DNA? Can you predict any potential mutations of the future cloned organism by looking at the DNA genome sequences that the organism will be produced from?
One of the original theories is that the problems are due to the clones starting out with shorter telomeres. Telomeres are repeated bases at the ends of chromosomes that get shorter each time the chromosome replicates itself. When they get too short, the genes on the chromosome can be replicated incorrectly, so that could be a source of damage for cloned DNA.
Newer research suggests that a big problem is, not damage to the genes themselves, but differences in the instructions for how the genes are activated. Many genes are inactivated in particular body cells, because the proteins that they produce aren't needed in that location. For instance, a skin cell doesn't need to produce digestive enzymes, so the genes for those enzymes might be deactivated. (One common way that genes are deactivated is by methylation. A methyl group is added to the DNA at the beginning of the gene so that the enzymes that make protein from the DNA can't attach to it properly.)
When an animal reproduces normally, there is very little methylation of the DNA in the zygote to start with. As the embryo develops differentiated parts, methylation occurs in different parts of the DNA depending on which genes that particular cell type will need to use.
However, when an animal is cloned from an adult cell, the cell has already differentiated. Some of the genes in the cell are inactive. That means that the embryo developing from the cloned cell may not be able to produce all the proteins it needs, because the genes for those proteins have already been deactivated. This article has a good general explanation of how gene expression differences can be a problem for cloned animals.
So the problems that the cloned animals are showing aren't necessarily mutations (changes in the DNA itself), but they sure can look like them. In most cases, offspring of cloned animals are perfectly normal, showing that the DNA itself is okay. When a cloned animal displays problems that look like mutations, there's a good chance that they're actually problems with how the gene is expressed.
The whole topic of how cells express different genes at different times is called "epigenetics", and it's an interesting area of research right now. We're learning a lot about how organisms develop, and how their environments can affect their genes. This PBS special shows a few examples of epigenetic differences between genetically identical twins.
Good luck with your project!
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