Tuesday, May 27, 2008

What's The Difference Between A Human And A Fruit Fly?

Not a whole lot, by objective standards. Wait... is this a trick question? Maybe. Turns out you can tell the difference by looking at protein interactions. (Technically, this is part of the "interactome".)

What's The Difference Between A Human And A Fruit Fly?
Fruit flies are dramatically different from humans not in their number of genes, but in the number of protein interactions in their bodies, according to scientists who have developed a new way of estimating the total number of interactions between proteins in any organism.

The new research, published May 13, 2008 in the Proceedings of the National Academy of Sciences journal, shows that humans have approximately 10 times more protein interactions than the simple fruit fly, and 20 times as many as simple, single-cell yeast organisms.

This contradicts comparisons between the numbers of genes in different organisms, which yield surprising results: humans have approximately 24,000 genes, but fruit flies are not far behind, with approximately 14,000 genes.

Surprisingly little seems to be known about how many actual genes different organisms have. It's relatively easy to figure out the size of an organism's complete genome, which is the number of base pairs in its DNA. (In just a single copy of the total genome, that is. Humans have 2 sets of chromosomes, hence two copies. But one bacterial species, Epulopiscium, has tens of thousands of copies of its genome. See here.)

You can find a table of a few different genome sizes here, and for more on genome size see here. Anyhow, this number varies dramatically. Humans have about 3.2 billion base pairs, but there's an amoeba, Amoeba dubia that has 670 billion base pairs, the largest size genome known. For a little more on genome size, see here.

Determining the actual number of genes is quite a bit harder, as some genomes contain a great deal of DNA that is not part of any gene. (This used to be called "junk DNA", but it's now realized that much of this DNA is actually important. We just don't know exactly what it's important for.) As we discussed here, it has finally been determined, after quite a bit of study, that there are about 20,500 human genes. (So the number 24,000 quoted above is an earlier, less exact estimate.)

For genomes which have not been studied as intensively as those of humans and fruit flies, our estimates on the number of genes are less certain. But, for example, corn has about 50,000 genes. So what is interesting is that most relatively complex organisms have numbers of genes numbering in the low tens of thousands.

An interesting question, then, based on the research cited at the beginning of this note, is why evolution has chosen to implement complexity through increasing the number of protein interactions rather than the number of actual genes.

At present, this question can only be speculated on. But it seems that some simple considerations of probabilities would lead us to have predicted the outcome.

Apparently, nature finds it relatively difficult to create new genes. New genes are created when a genome acquires two or more copies of an existing gene. Usually additional copies come about (over multiple generations) when it is useful to an organism to produce larger amounts of a certain protein, since two copies of a gene would be expected to result in about twice as much of its corresponding protein.

But as soon as there are multiple copies of any gene, the copies can start to diverge from each other in their exact sequence, if the protein they originally code for becomes less critical. The result is two or more genes that gradually, over many generations, code for slightly different proteins, which may come to have very different functions.

However, what we apparently have to conclude from the fruit fly research, is that changes to an organism's phenotype (roughly, its physical form) are rather more likely to occur when genetic changes are so slight that they don't lead to actual new genes, but instead merely large enough to alter a protein only enough to change how it interacts with some, probably just a few, other proteins.

We still don't know how many distinct proteins are actually produced, even in humans. We do know the number is much larger than the number of different genes, because of alternative splicing. In humans, this number might be in the hundreds of thousands. Whatever the actual number (call it N) is, the number of possible interactions within the set is astronomical, since the number of distinct protein pairs is almost N2/2.

So it stands to reason, just on a crude probabilistic estimate, that a minuscule change in a protein, due to a change of a single amino acid in its sequence, is far more likely to affect how the protein interacts with some other protein than how it significantly affects the protein's main function.

The net is that small phenotype-altering changes to existing genes are much more likely to result from changes to protein interactions than from development of entirely new genes.

Further reading:

Web of protein interactions reflects human complexity better than number of genes – very good 5/12/08 article on this research at Science News

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