Thursday, April 02, 2009

Dynamic Genomes

There may have been a time in the past when scientists imagined a static genome that only changed slowly over millions of years. However, beginning in the 1960's we began to see the genome as a much more dynamic entity. The first evidence of this kind of genome came with the discovery of huge amounts of variation between individuals in a species.

This was followed by the discovery of transposons and junk DNA. We began to see genomes as rather sloppy DNA molecules with lots of pieces hopping in and out on a timescales of generations. We began to realize that many genomes were full of pseudogenes.

Chromosomal rearrangements such as inversions, duplications, and translocations were documented. In mammals, many of them were associated with cancer, thalassemias, and other diseases but the general impression was that these rearrangements of genetic material were quite common. Indeed, some non-disease examples began to accumulate in the literature. Clear evidence of normal rearrangements associated with regulation and development—including mating type switching in yeast, immunoglobulin rearrangements in mammals, chorion gene amplification in Drosophila, and antigenic variation in trypanosomes—reinforced the idea that the genome was not static.

Most of this information was incorporated into the textbooks. For example, by the early 1980's Benjamin Lewin' textbook Genes had an entire group of chapters under the heading "The Dynamic Genome: DNA in Flux."

We soon learned about the expansion and contraction of repetitive sequences in the human genome. These observations eventually gave rise to DNA fingerprinting whereby every individual could be uniquely identified by variations in the genome.

By the early 1990's the concept of the dynamic genome had become so widely entrenched among molecular biologists that when Singer and Berg published "Genes and Genomes" they felt obliged to inject a note of caution. While genomes are dynamic at the scale of species evolution, the typical genome of an individual is not subject to significant rearrangements.

Outside of molecular biology, the idea that genomes were flexible never seemed to catch on. Most people thought of genomes as relatively static entities that didn't change much over millions of years. In part, they adopted this position because they still placed a great deal of emphasis on the power of natural selection. If genomes were well-adapted then why would they change? Part of the skepticism about junk DNA stems from the belief that selection will eliminate useless DNA.

Recent developments have stirred many people to re-think their concept of genomes. For example, Sandra Porter of Discovering Biology in a Digital World recently asked, "What if everything you thought you knew about the genome was wrong?."

To the extent that such questions acquaint people with the concept of a dynamic genome, they are good. On the other hand, if such questions lead to the unthinking acceptance of alternative splicing, superabundant transcription, and a plethora ot RNAs, they are bad.


3 comments:

  1. Nice. I love this topic.

    What's the mechanism of CNV outside of the context of disease like cancer?

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  2. That's a lot of left-handed junk DNAs on your illustration :-)

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  3. Heh! Good catch, DK!

    I don't know if it's been proven whether Z-DNA occurs in vivo, but it's certainly not THAT common.

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