Genes that allow nerve cells to communicate may have come from bacteria eons ago

Some of the genes that allow nerve cells and some other types of cells to send elaborate chemical messages to each other appear to have been transferred to animals or their immediate ancestors from bacteria eons ago, according to a study by researchers from the National Library of Medicine and the National Institute of Child Health and Human Development, both part of the National Institutes of Health.

Specifically, the genes contain the information needed to make enzymes, which, in turn are crucial for making the complex molecules that cells use to communicate with each other. These cell-signaling molecules play a role in learning, memory, mental alertness, sleep patterns, and allergic responses.

The study was published on the web at http://www.sciencedirect.com and will appear in the July issue of Trends in Genetics.

"By studying these enzymes in bacteria, we may be able to get a better idea of how they work in human beings," said the study's first author, Lakshminarayan Iyer, Ph.D., Research Fellow, of the National Center for Biotechnology Information of the National Library of Medicine (NLM).

Bacteria are single celled organisms. In plants and animals, DNA is contained in a membrane bound compartment called the nucleus. The DNA of bacteria is not contained within a nucleus.

For the study, the researchers conducted a comprehensive search of the National Library of Medicine's genetic databases. They identified a group of genes needed to make some enzymes involved in the manufacture of the chemical messengers that cells use to communicate. The genes are present in bacteria and in vertebrate animals, but with a few exceptions, not in plants, or other complex living organisms. The search was prompted by the group's earlier observation that the enzyme arylalkylamine N-acetyltransferase (AANAT) was present in animals, bacteria, and yeast, but in no other living organisms. AANAT is used to make melatonin, a hormone that regulates the body's cycles of sleeping and waking.

The researchers also identified genes for enzymes that are involved in the manufacture of the following chemical messengers:

• acetylcholine — involved in learning and memory, muscle contraction,

• dopamine — the absence of which results in Parkinson's disease

• norepinephrine and epinephrine — involved in alertness, vascular tone

• serotonin — involved in mood,

• glutamate — involved in alertness

• nitric oxide — involved in many bodily functions, including blood pressure regulation

• histamine — involved in the allergic response

The bacterial genes may have been transferred to the organisms that were the ancestors of animals more than a half billion years ago, explained another of the study's authors, David Klein, Ph.D., a melatonin researcher at the National Institute of Child Health and Human Development (NICHD).

It is not known how the genes were transferred, but Dr. Klein theorizes that one form of transfer took place during the reproductive cycle, with the genes having been incorporated into either sperm or egg cells or incorporated shortly after fertilization. It's possible that the transfer could also represent a form of infection where genetic material is transferred into these reproductive cells and thereby into the entire genome of the recipient.

Bacteria do transfer genes to other bacteria, by means of a circular DNA molecule known as a plasmid. However, Dr. Klein said, bacteria are not believed to be capable of passing plasmids to animal cells.

The study's authors offered an alternative explanation for the fact that some genes are present only in bacteria and animals. According to this explanation, all living organisms once possessed these genes as well, and most lost them. However, the authors wrote that it is unlikely that such a large group of living organisms could have lost so many genes.

An understanding of how the enzymes function in bacteria may provide insight into how they function in animals, Dr. Klein said. All the enzymes may be important to bacteria because they provide a detoxification function — they make chemical changes within the bacteria that eliminate potentially toxic substances. AANAT, he said, is present in both the pineal gland, located in the brain, and in the retina of human beings and other primates. In the pineal gland, AANAT plays a role in manufacturing melatonin. However, AANAT in the retina does not manufacture melatonin. Dr. Klein suspects that, in the retina, AANAT may have a role in neutralizing and eliminating toxic substances. He is currently investigating whether a disruption in AANAT function plays a role in the development of macular degeneration, a disease that impairs vision and that may result in blindness.

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