Role of DNA in adult animals?

Factual Questions
1

I tried to search the SDMB but “dna” is too short. Google has too much stuff for me to make sense of - can a biologist Doper help me out?

What role does DNA play in the daily existence of a fully-grown organism? All I remember from my entry-level biology classes is that DNA is a genetic “blueprint” for how an organism is built - made up of the two halves of the parents’ split DNA molecules.

Well - if it is a blueprint, what role does it play once the “building” is done? A house doesn’t “need” its blueprints after it is built, if you follow me. But I hear references to how gene therapy can help adults with certain diseases, and other references that lead me to believe that DNA does play a role in “built” animals.

What is that role? If new/modified DNA is introduced into an organism, what process occurs that would to the targeted changes?

Thank you!

2

DNA within an adult organism is constantly being used to produce proteins (functional DNA, that is, much of an animal’s DNA will be non-coding “junk” DNA, whose function is unclear at best).

The cell isn’t just built once - the DNA is in a constant state of use where it will be used to produce the proteins that exist in the cell, the products of the cell that will be exported to other parts of the body (e.g. insulin is produced and released into the bloodstream by cells in the Islets of Langerhans in your pancreas), and the DNA is often in a state of replication - being duplicated so that a copy can be passed on to the daughter cells if it is a cell in your body which can still divide.

Modified DNA can be introduced, and will produce new/modified proteins under certain circumstances - this is what happens when you get infected with a DNA virus - your cell turns from a factory for your own body into a factory for new viruses, following the instructions inserted by the virus into your DNA.

3

Sorry, I don’t think I addressed this part in my post.

A far better analogy than the blueprint → house analogy would be to think of each cell in your body like your local fast food restaurant.

In order to produce a supply of burgers for its customers, the restaurant needs to process incoming raw materials, ensure that it is suitably modified for consumption, needs to fix the soda machine if it gets broken, so it might need to order spare parts (and imagine that the spare parts are built on-site in the restaurant!), it needs new workers from time to time, the tables need to be wiped down, etc. etc.

It’s not like the cell is “built” and then the DNA’s job is done. There’s a lot going on in the daily life of the cell that requires the instructions from the DNA. Plus a new cell will often need to be produced. For example, red blood cells only last an average of about 30 days in your body, so you need a constant supply of new cells to replace the old as they die.

It works much better to think of the DNA as the franchise instruction manual for a fast food restaurant, managing and governing ongoing processes like preparing food from raw materials, repairing machines, and recruiting new workers, rather than as blueprints for a house that is built and stands with minimal maintenance for a long time.

4

There is a tremendous role for DNA in the management of the minute-to-minute processes of a cell. There is a baseline level of RNA transcription off the DNA which is necessary for a cell to stay alive.

Every cell responds to internal and external changes constantly. A few examples would be the transition from unfed to fed, learning and memory, and normal homeostasis like blood pressure, fluid, heart rate, and temperature regulation. Many of these depend on the reception and the sending of hormonal signals, and hormones are either proteins themselves or synthesized by protein enzymes.

Think of something reasonably simple – blood sugar regulation. In an unfed normal state, blood sugar is low, glucagon (protein fragment) is synthesized to set off a number of biosynthetic pathways (depends on enzymes) to make new glucose, break down glycogen, and if necessary start fat metabolism. Eating a sugar load triggers receptors which signal to the pancreas to secrete insulin (protein fragment). Insulin binds to receptors on cells which stimulate the cells to uptake glucose (proteins required). Through asignal transduction pathway, the activated insulin receptor can switch off the biosynthetic pathways of an unfed state and turn on synthetic pathways such as fat and glycogen anabolism. All of these things require transcription (to make RNA from DNA, which is usually short-lived) and translation to turn RNA into protein.

Also, almost everything in the body has normal wear and tear. Proteins, lipids, even bone is recycled and replaced regularly. To do so requires lots of baseline level of gene transcription and protein synthesis.

DNA indeed does contain a blueprint. But don’t think of your body like a house, think of it like a city or a country. There is constant renewal, replacement, and new construction to deal with changing demographics and stresses. All of these need the blueprints as well.

5

Celullar replication and repair are ongoing processes in adults. Many cell types in the body have lifespans on the order of weeks.

As was noted, DNA also codes for “gene products”. One mechanism for controlling the levels of these proteins in the cell (or available for export) is an elaborate control system of “variable transcription” or controlling the rate messenger RNA is copied from each DNA template gene. [mRNA is quickly degraded in the cell, so only recently produced cpies are active). DNA also codes the structure of many other kinds of RNA (e.g. the RNA backbone of the protein-synthesizing ribosomes) that serve essential cell functions other than carrying the code for gene products.

DNA performs quite a few other functions as well. The telomeres (long chains of repeating sequences at the ends of chromosomes) are believed to be one of the mechanisms by which the number of generations of a cell is controlled, and probably impacts aging in the mature adult. You lose some telomeres every time the cell divides after fertilization. (But a full set is generated in the DNA of gametes or “sex cells” for the next generation)

Basically, DNA is the “brain” of the often short-lived cell (more accurately, it’s the cross generational lore) While it may appear to an alien that only a certain specialized adult humans have any need for the brain once they achieve their mature physical state, it can actually be helpful in many subtle ways throughout the life cycle :wink:

6

This is great - thanks you guys! My ignorance is being fought even as we speak.

Okay, follow up: the explanations so far make sense to me and the analogies work. But how does DNA move from cell to cell? I think of oxygen, nutrients, etc., moving from lung/digestive tract into the bloodstream and via that to throughout the body.

I also think I get the revised analogy of DNA being not only blueprints, but an ongoing replenishment “manual” so new protein cells can be built and added to “inventory” as needed, if you will.

But DNA exists in cells - and once a cell is created with its DNA “manual” in it, that’s it, right? If modified DNA is introduced into an organism, how is that new DNA circulated and how does it replace the older DNA? It’s not like the body’s fast-food franchise (to use wevets’ analogy) can just circulate a new CD-ROM with the updated instruction manual on it and say “throw the other/old one away.” Can you spell that one out for a non-bio civilian like me?

Thanks again!

7

that’s “protein molecules”, or probably better stated, “proteins” - sorry…

But anyway, I hope my follow-on question makes sense!

8

It doesn’t (except in the special case of sperm meeting egg). Each cell has its own complement of DNA which it uses for its specific purposes.

Hence, an individual can be identified (and, in theory, cloned) from the DNA present in a single cell.

9

My point exactly - so how can modified DNA be introduced in an organism and have an influence? Or am I misundertanding how modified DNA can address certain genetic conditions…

10

Wait, I just thought of another special case that may be closer to what you’re asking about.

A virus reproduces by injecting its own DNA into a cell. It also injects specialized proteins that will cut the cell’s own DNA, and splice the viral DNA into it, like it was a filmstrip. The cell is then highjacked into making parts of the virus, the splicing protein, the viral casing and the viral DNA, and sending new virus out into the surrounding environment. This often kills the host cell, but not always. In fact, our DNA contains huge portions of viral DNA that’s stuck around, passing through the generations, for millions of years!

Scientists are trying to learn how to use this viral splicing technique to deliver beneficial DNA to cells (like a gene that’s missing in a person with a disease), but so far most trials have had lethal side effects.

11

DNA never moves from cell to cell. Each cell has the entire set of DNA for that species.

However, parts of that DNA library are turned off in different types of cells. So the recipe to turn an embryonic cell into a nerve cell are present in every cell, but those genes are only turned on in nerve cells.

12

What you are talking about is gene therapy.

The simplest explanation is that we don’t know exactly how it would work yet. But we have a pretty good idea of what is required.

As others have mentioned, the easiest way to introduce DNA into a cell would be a virus. Viruses are little DNA-injecting machines, so we have taken certain viruses, gutted their genomes, and can put our piece of DNA in there in place. Viruses aren’t really alive so they don’t really need any genes to survive (although there is size constraints and DNA binding sites in the viral genome that are necessary for correct packing and such). A regular virus turns a cell into a virus-producing factory. A gutted virus would introduce its DNA, we would hope for incorporation, and we would go from there.

Let’s take twoan example. It is not one that you are probably familiar with, but it is one of the more tractable genetic diseases for gene therapy – ornithine transcarbamylase (OTC) deficiency. This disease is from an inborn deficiency of the enzyme ornitihine transcarbamylase. The goal is to reintroduce this enzyme into a tissue that could get rid of the toxic accumulating substances – the liver. So a modified adenovirus, the type that causes a common cold, was produced carrying that gene and not a lot else. The hope was that this virus would infect the liver (it carried proteins that bound liver cells), and introduce the enzyme. These cells would divide and provide enough OTC to get rid of the toxic substances. Unfortunately, one of the test subjects, a 17 year old boy named Jesse Gelsinger, developed hepatic failure and went into ARDS and died. The body responded to the virus in a bad way, and perhaps responded as well by attacking its own liver and this led to multi-system organ failure.

Besides that tragic failure, there are other roadblocks. Take a disease like cystic fibrosis – one would have to target a subpopulation of stem cells in the respiratory epithelium. This is because the respiratory epithelium is constantly regenerating and being shed. So targeting the outer layer of cells won’t cut it, you have to target the few stem cells right on the basement membrane. Unfortunately, these cells are mostly dormant, are only a tiny fraction of the total population, and are usually resistant to any kind of uptake.

There are other ways to introduce new genetic material besides with viruses. One of the more successful is for immune deficiencies and cancer syndrom. Making transgenic cells in a culture dish is a lot easier than doing it in a patient’s bone marrow. So one takes out a bone marrow sample, cultures it, introduces new genes, expands the population, make sure everything is going OK. Then one kills the bone marrow of the patient (with high doses of chemotherapy) and reintroduces the cultured transgenic bone marrow. Unfortunately, a few cases of leukemia have resulted from such an approach. There are also other emerging technologies – gene guns and naked DNA introduction and DNA-coated beads and the like.

It would be next-to-impossible to change the DNA in every cell at the same time. Gene therapy, for now, is just focusing on correcting mutations and broken genes in affected tissues.

13

Ah - I get it. It is not about circulating new DNA which then replaces old DNA; it about using an existing method - viruses - that splice new “instructions” into a cell’s DNA, so as that cell goes through it’s normal “re-inventorying construction” process for proteins, the desired modifications get made.

If I missed it, let me know - but otherwise - cool!

14

Yeah, there needs to be a distinction made between the genome and other, extragenomic DNA bits. The genome, in the cell’s nucleus, is basically the same in every cell in the person’s body, and is first created at fertilization when the egg and sperm pronuclei fuse. During mitosis, it is copied and one copy is distributed to each of the two daughter cells. Each cell is responsible for copying and repairing its own genome. If a mutation arises in a cell which gives rise to 1000 daughter cells, all 1000 of those daughter cells will carry the same mutation (if it is not repaired). Think cancer.

15

Well, everyone’s already done an admirable job covering it for you, so I have to come up with something only vaguely related to contribute. The genes that are always “on” in any cell to keep it up and running are called housekeeping genes. We use them in the lab a lot as internal controls. Since you know that those housekeeping RNAs (copied from the DNA) are present, you amplify one of them just to prove that you have isolated good, useable RNA and that your reaction is working correctly.

I got nuthin’.