The scientists found that even small changes in functionally inactive “junk DNA” are sufficient to create essential control elements in gene regulation known as enhancers.
Genetic variation in humans is not primarily due to differences in the 1.5 per cent of DNA that code for gene products. Rather, experts today assume that most differences between humans are the result of changes in those DNA sequences that control gene regulation, in example the formation of gene products such as proteins. Enhancers are an essential component in the control mechanism of gene regulation. Changes in enhancers can lead to disease and malformation; on the other hand, they carry the potential for evolutionary innovation.
Michael Eichenlaub and Doctor Laurence Ettwiller have shown that such innovation can occur through “de novo” formation of new enhancers, arising from slight changes in the DNA that had no regulatory activity before. This finding contrasts with the general view amongst evolutionary scientists that novelty mainly arises from modification of pre-existing functional components of the genome.
This view has generally led scientists to focus their attention on the loss and modification of functional elements, neglecting variations in the “junk DNA”, which makes up about 97 per cent of genetic information. “This work brings such neglected regions of the genome to the forefront as a putative ‘breeding ground’ for new enhancers“, says Ettwiller, who headed the study.
To prove the existence of those new enhancers, the Heidelberg scientists designed an assay in the Japanese freshwater fish Medaka to capture rare events in which the sequence of a novel enhancer could be traced to other related species and validated these sequences experimentally. In several cases, they found evidence of a “de novo” formation of new enhancers. “Even though this study has been conducted in fish, the same mechanisms apply to the human genome”, says Ettwiller.
“The study demonstrates that the slow but persistent changes that occur in DNA in each generation are sufficient to eventually lead to the apparition of new functions”, explains Eichenlaub. “The methods we have established here could help to identify the changes that have contributed to the evolution of our species and explain the 1.23 per cent of the genetic information that differ between the chimp’s and our genomes”, adds Ettwiller.
MEDICA.de; Source: Ruprecht-Karls-Universität Heidelberg