Researchers have shed more light on the evolution of the human genome, by answering a difficult as well as relevant genomic question: Which of the thousands of long stretches of repeated DNA in the human genome came first, and which are the duplicates?
The new study, from an interdisciplinary team led by biologist Evan Eichler from the University of Washington School of Medicine and computer scientists Pavel Pevzner from University of California, San Diego, provides the first evolutionary history of the duplications in the human genome that are partially responsible for both disease and recent genetic innovations.
According to the researchers, their work marks an important step towards a better understanding of what genomic changes paved the way for modern humans, when these duplications occurred and what the associated costs are - in terms of susceptibility to disease-causing genetic mutations.
Genomes have an extraordinary ability to copy a long stretch of DNA from one chromosome and insert it into another region of the genome. The resulting chunks of repeated DNA, called "segmental duplications," contain many evolutionary secrets and detecting them is a difficult biological and computational challenge with implications for both medicine and our understanding of evolution.
To decipher the duplication code and find out which of the DNA segments are originals - ancestral duplications, and which are copies - derivative duplications, the researchers looked at both algorithmic biology and comparative genomics.
"Identifying the original duplications is a prerequisite to understanding what makes the human genome unstable. Maybe there is something special about the originals, some clue or insight into what causes this colonization of the human genome," Nature quoted said Pevzner, as saying.
The researchers located the ancestral origin of more than two thirds of these long DNA duplications, and concluded with two major findings.
First, the researchers suggest that specific regions of the human genome experienced elevated rates of duplication activity at different times in our recent genomic history. This contrasts with most models of genomic duplication which suggest a continuous model for recent duplications.
Second, the researchers proved that a large fraction of the recent duplication architecture centers around a rather small subset of "core duplicons" - short segments of DNA that come together to form segmental duplications. These cores are focal points of human gene/transcript innovations.
"We found that not all of the duplications in the human genome are created equal. Some of them - the core duplicons - appear to be responsible for recent genetic innovations the in human genome," explained Pevzner.
"We note that in 4 of the 14 cases, there is compelling evidence that genes embedded within the cores are associated with novel human gene innovations. In two cases the core duplicon has been part of novel fusion genes whose functions appear to be radically different from their antecedents," the authors wrote in their paper.
In the future, the researchers plan to continue their exploration of evolution.
"We want to figure out how the human genome evolved. In the future, we will combine what we know about the evolution within genomes with comparative genomics in order to extend our view of evolution," said Pevzner.
The findings are published online in Nature Genetics.'