Study provides new insights into an ancient mechanism of mammalian evolution

Jan 12, 2012
Over 150 million years of evolution, CTCF binding events have been added to the genome through repeated waves of retrotransposon expansion. Panel A shows examples of these events (top) and a sample CTCF binding event (bottom) that dates from before mammals began to branch out. Panel B shows in more detail how the CTCF protein interacts with mouse binding motif.

A team of geneticists and computational biologists in the UK today reveal how an ancient mechanism is involved in gene control and continues to drive genome evolution. The new study is published in the journal Cell.

To function properly, mammalian tissues require the protein CTCF, which has several key activities including the regulation of genes and interaction with proteins in the cell's nucleus to alter . CTCF acts by binding to DNA and plays a role in diseases such as and cancer. However, very little is known about the origin of the that are bound by CTCF.

In this study, the researchers used samples from six mammals (human, macaque, mouse, rat, dog, and short-tailed ) to pinpoint where CTCF binds to each genome. They discovered around 5000 sites that are present in most cell types and tissues, and that have not changed over hundreds of millions of years of . Because these CTCF binding sites are conserved throughout evolution, the researchers believe that many might play an important role in .

The team found an even larger number of locations where CTCF binds DNA in only one lineage or a single species. These additional sites represent a signature of important since our last common ancestor – legacies, in some cases, of the evolutionary path to humans. These newer CTCF sites are embedded inside virus-like stretches of DNA called 'retro-transposons'. Retro-transposons use a copy-paste mechanism to spread copies of themselves throughout the genome.

"We developed a new, integrated model of CTCF evolution, which explains the origin of these 5000 highly conserved CTCF binding events in mammals," said Paul Flicek of the European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI) and the Wellcome Trust Sanger Institute. "Taken together, our findings provide fascinating insight into an ancient mechanism of evolution that is still actively changing our genome."

"CTCF is a key regulator involved in chromatin and gene expression remodelling, both of which are perturbed in the development of cancer. The gene expression and chromatin changes in cancer have also recently been relied on to predict the outcome of specific cancer treatments, which is why it is so important to have a detailed understanding of how particular parts of the genome are resistant or plastic to changes," said Duncan Odom of Cancer Research UK and the Wellcome Trust Sanger Institute.

The retro-transposon's copy-and-paste behaviour has long been considered totally self-serving. However, the study showed that when a retro-transposon containing a CTCF-binding sequence spreads around a mammal's genome, it can deposit functional CTCF binding sites in novel locations, altering the activity of distant genes.

"We looked at six mammalian species representing primates, marsupials, rodents and carnivores, and discovered a simple mechanism that they all use to remodel their DNA," explained Petra Schwalie of EMBL-EBI. "We also found that our distant ancestors also experienced the same complicated relationship between CTCF and retro-transposons."

Using molecular palaeontology techniques, the researchers were able to identify fossil traces of older retro-transposon expansions in the DNA around the shared CTCF binding locations, and showed that this process has been active for hundreds of millions of years.

Explore further: Vermicompost leachate improves tomato seedling growth

More information: Waves of repeat-driven CTCF binding expansions have shaped mammalian genomes. Schmidt D., Schwalie P., Wilson M.D., et al. Cell 2012, DOI: 10.1016/j.cell.2011.11.058 dx.doi.org/10.1016%2Fj.cell.2011.11.058

Related Stories

Good fences make good neighbors

May 14, 2009

Our genome is a patchwork of neighborhoods that couldn't be more different: Some areas are hustling and bustling with gene activity, while others are sparsely populated and in perpetual lock-down. Breaking ...

'Insulator' helps silence genes in dormant herpes virus

May 02, 2007

By adulthood, most people have suffered at least one bout of painful cold sores brought on by the Herpes simplex virus 1, also known as HSV-1. After the initial infection, the virus usually remains in the body, hiding out ...

Recommended for you

Vermicompost leachate improves tomato seedling growth

Nov 21, 2014

Worldwide, drought conditions, extreme temperatures, and high soil saline content all have negative effects on tomato crops. These natural processes reduce soil nutrient content and lifespan, result in reduced plant growth ...

Plant immunity comes at a price

Nov 21, 2014

Plants are under permanent attack by a multitude of pathogens. To win the battle against fungi, bacteria, viruses and other pathogens, they have developed a complex and effective immune system. And just as ...

Evolution: The genetic connivances of digits and genitals

Nov 20, 2014

During the development of mammals, the growth and organization of digits are orchestrated by Hox genes, which are activated very early in precise regions of the embryo. These "architect genes" are themselves regulated by ...

Surrogate sushi: Japan biotech for bluefin tuna

Nov 20, 2014

Of all the overfished fish in the seas, luscious, fatty bluefin tuna are among the most threatened. Marine scientist Goro Yamazaki, who is known in this seaside community as "Young Mr. Fish," is working to ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.