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Ask an Embryologist: Genomic Mosaicism


A reader writes to ask:

In a recent ENV post, Casey Luskin observed that humans have a "few thousand" different cell types. Here is my simple question: Does the DNA sequence in one cell type differ from the sequence in another cell type in the same person? Do we really know that the DNA sequence in one person is the same all over his body? I am inclined to guess that the answer is: "No one is quite sure."

The simple answer is: We now know that there is considerable variation in DNA sequences among tissues, and even among cells in the same tissue. It’s called genomic mosaicism.

In the early days of developmental genetics, some people thought that parts of the embryo became different from each other because they acquired different pieces of the DNA from the fertilized egg. That theory was abandoned — in large part because of early nuclear transplant experiments, which showed that the nuclei of some differentiated cells, when transplanted into an egg from which the nucleus had been removed, could support full development.

Since the nuclei of at least some differentiated cells apparently contained all the DNA needed to make an entire organism, "genomic equivalence" — the idea that all the cells of an organism (with a few exceptions, such as cells of the immune system) contain the same DNA — became the accepted view.

I taught genomic equivalence for many years. A few years ago, however, everything changed. With the development of more sophisticated techniques and the sampling of more tissues and cells, it became clear that genetic mosaicism is common.

Here is the Abstract of a 2012 article ("Extensive genetic variation in somatic human tissues") in Proceedings of the National Academy of Sciences USA (it’s open access).

Genetic variation between individuals has been extensively investigated, but differences between tissues within individuals are far less understood. It is commonly assumed that all healthy cells that arise from the same zygote possess the same genomic content, with a few known exceptions in the immune system and germ line. However, a growing body of evidence shows that genomic variation exists between differentiated tissues. We investigated the scope of somatic genomic variation between tissues within humans. Analysis of copy number variation by high-resolution array-comparative genomic hybridization in diverse tissues from six unrelated subjects reveals a significant number of intra-individual genomic changes between tissues. Many (79%) of these events affect genes. Our results have important consequences for understanding normal genetic and phenotypic variation within individuals, and they have significant implications for both the etiology of genetic diseases such as cancer and for immortalized cell lines that might be used in research and therapeutics.

This is not the same as the old idea that DNA fragmentation causes embryo differentiation. From what I now know as an embryologist I would say that the truth is the opposite: Tissues and cells, as they differentiate, modify their DNA to suit their needs. It’s the organism controlling the DNA, not the DNA controlling the organism.

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