Natural Transgenics and DNA Ingestion

NATURAL TRANSGENICS AND DNA INGESTION

Historically speaking, we are all transgenic. The human genome contains a significant number of genes of bacterial origin. These have presumably been picked up at various stages in evolutionary history from assorted bacteria. In addition, we carry quite a few genes that came originally from other higher organisms, some of which have been transmitted by retroviruses. Such movement of genes between organisms that are not direct descendants is generally known as lateral or horizontal gene transfer, but might just as well be called “natural transgenesis.”

There are two major pathways for naturally acquiring genetic material from other organisms. One is by viral transduction and the other is by direct intake of DNA. In microorganisms DNA from the environment may be taken up by transformation. In the case of animals, DNA is constantly ingested along with other components of the diet. Certain protozoa such as Paramecium and some amoebas live by ingesting bacteria. It is thought that several genes involved in fermentative metabolism in Entamoeba are derived from such ingested bacteria.

Humans and other mammals, whether carnivorous or vegetarian, are constantly eating food that contains substantial amounts of DNA. Although it is generally assumed that ingested DNA is degraded into nucleotides in the intestinal tract, this is not entirely true. Recent findings suggest that a very small proportion of the DNA survives as fragments of moderate size (up to 1000 base pairs) and actually crosses the intestinal wall into the bloodstream of the animal in this form. At least transiently, DNA from food can be traced to several different organs and can also cross the placenta to fetuses and newborns.

DNA from the bacterial virus M13 and the gene for green fluorescent protein have been used as test molecules. More recently, naturally occurring DNA sequences for the plant-specific ribulose-1,5-bisphosphate carboxylase (Rubisco) gene have been tracked by PCR. All of these foreign DNA sequences have been found both in the bloodstream and in the cell nuclei of various tissues in animals that ingested the DNA. Sometimes the foreign DNA appears to be integrated into host chromosomal DNA. However, so far no evidence for expression of genes carried by ingested DNA has been found, nor has incorporation into the germline been seen for DNA eaten by mice. The overall likelihood of food-borne DNA infiltrating the genome and being expressed is unknown, although it seems low. Nonetheless, because vast numbers of animals have eaten DNA every day of their lives over millions of years, it seems likely that this must occur now and then. Furthermore, the fact that our genomes do include a small percentage of foreign genes argues that germline insertion does occur, albeit very rarely.

From a purely theoretical viewpoint, we should remember that living cells contain much more RNA than DNA. Thus the amount of RNA ingested in the food is at least 10-fold greater than the amount of DNA. Whether any of this RNA survives long enough to cross the intestinal wall and enter animal cells has so far not been investigated. Reverse transcriptase from the assortment of retroelements present in most animal genomes could in theory reverse transcribe such incoming RNA, so generating a DNA copy that might occasionally integrate into the host cell genome.