|Clues to the Human Condition
Groundbreaking Study Indicates Epigenetic Evolution Occurs
In an exciting new publication in PLoS Genetics, CHORI scientists Lucia Carbone, PhD, Pieter de Jong, PhD, David Martin, MD, and their colleagues, demonstrate for the first time by analyzing DNA sequences in the northern white-cheeked gibbon that epigenetic states of repeated elements can impact genome evolution. This new information is important not only for understanding mammalian evolution, but also to discover how epigenetic changes in DNA might cause human disease, such as cancer.
Everyone knows that the phenotypes seen in different individuals - their hair or eye color, for example - are the result of which genotypes, or sequences of DNA, they have inherited from their parents. The idea of epigenetics, however, is that the same DNA sequence might behave differently in different cells, species or individuals within a species.
"Genome evolution is the description of a how a genome changes through evolution, and the way in which you can actually study this is by comparing genomes of different species to discover the most important regions," explains Dr. Carbone. "For example, DNA sequences that are identical in human and mouse are most likely to have an essential function for mammalian organisms."
The advent of epigenetics, however, has raised the question of whether other DNA modifications that don't involved a change in DNA sequence could be influencing genome evolution, as well. The results of the new study, which Dr. Carbone recently presented at one of the most prestigious genome conferences in the world, the Biology of Genomes (Cold Spring Harbor), suggest for the first time that the answer to that question is undoubtedly, Yes.
"We're interested in studying gibbons because while they are evolutionarily very close to us, they have a 20-fold increase in chromosomal rearrangments as compared to humans and other primate species," Dr. Carbone says.Chromosomal rearrangments occur when two or more chromosomes break and recombine in ways they shouldn't. As Dr. Carbone explains, her goal in the current study was to try to understand why this happened so often during the evolution of gibbon species and possibly identify new mechanisms to explain such chromosome instability. To do so, Dr. Carbone focused on analyzing the DNA breakpoints - those sequences in which the DNA unexpectedly broke and recombined.
The relationship between undermethylated repeats and chromosome rearrangements is of particular interest because recent studies have shown that a similar relationship may be present in cancer cells.
"Either increased or decreased methylation has been a consistent finding in human tumors and it is thought to be associated with chromosome rearrangements; what we find in the gibbon is an indirect way to show that undermethylated repeats may be responsible for genome instability," says Dr. Carbone."Now we can actually use the gibbon to create a new model of chromosome evolution that we can apply to other species."
Tuesday, May 17, 2011 8:19 AM