The vast majority of the human genome consists of DNA without any apparent function, earning it the nomenclature of “junk DNA”. But at last a study conducted by the scientists Dr Laurence Ettwiller and Michael Eichenlaub at Heidelberg University's Centre for Organismal Studies now highlights this “dark matter” activation of the genome as a resource for evolutionary novelty.

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. The results of the study are published in “PLoS Biology”

Genetic variation in humans is not primarily due to differences in the 1.5% of DNA that code for gene products. Rather, experts currently assume most differences between humans are the result of changes in those DNA sequences that control gene regulation, that is 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; but they also carry the potential for evolutionary innovation.

Michael Eichenlaub (left) and Laurence Ettwiller (right) show that such innovation can occur through “de novo” forma­tion of new enhancers, emerging 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.

The view generally led scientists to focus attention on loss and modification of functional elements, neglecting variations in the “junk" DNA, which makes up about 97% of genetic information.

“This work brings such neglected regions of the genome to the forefront as a putative ‘breeding ground‘ for new enhancers,“ says Laurence 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 (embryo left) to capture rare events where 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% of the genetic information that differ between the chimp’s and our genomes,” adds  Ettwiller.


Above: Japanese freshwater fish Medeka. Image Etwiller/Eichenlaub.