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Time lapse of a developing drosophila embryo. (Credit: Carlos Sanchez-Higueras/Hombría lab/CABD)

Every animal, from an ant to a human, contains in their genome pieces of DNA called Hox genes. Architects of the body, these genes are keepers of the body’s blueprints; they dictate how embryos grow into adults, including where a developing animal puts its head, legs and other body parts. Scientists have long searched for ways to decipher how Hox genes create this body map; a key to decoding how we build our bodies.

Now an international group of researchers from Columbia University and the Spanish National Research Council (CSIC) based at the Universidad Pablo de Olavide in Seville, Spain have found one such key: a method that can systematically identify the role each Hox gene plays in a developing fruit fly. Their results, reported recently in Nature Communications , offer a new path forward for researchers hoping to make sense of a process that is equal parts chaotic and precise, and that is critical to understanding not only growth and development but also aging and disease.

“The genome, which contains thousands of genes and millions of letters of DNA, is the most complicated code ever written,” said study co-senior author Richard Mann , PhD, principal investigator at Columbia’s Mortimer B. Zuckerman Mind Brain Behavior Institute and a faculty member in the Department of Systems Biology . “Deciphering this code has proven so difficult because evolution wrote it in fits and starts over hundreds of millions of years. Today’s study offers a key to cracking that code, bringing us closer than ever to understanding how Hox genes build a healthy body, or how this process gets disrupted in disease.”

Read the full article at the Zuckerman Institute

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Gradually eliminating low-affinity binding sites identified by NRLB (from left to right) results in a gradual reduction of gene expression (white); Credit: Mann Lab/Columbia’s Zuckerman Institute

As reported  by the Zuckerman Mind Brain Behavior Institute, Columbia University researchers have developed a new computational method for deciphering DNA’s most well-kept secrets, and this new algorithm may help find the links between genes and disease. 

The researchers included lead PI at Zuckerman  Richard Mann , PhD, with collaborator, Harmen Bussemaker , PhD, both faculty members of the Department of Systems Biology. They recently published their findings in the Proceedings of the National Academy of Sciences .

“The genomes of even simple organisms such as the fruit fly contain 120 million letters worth of DNA, much of which has yet to be decoded because the cues it provides have been too subtle for existing tools to pick up,” said Mann, who is also Higgins Professor of Biochemistry and Molecular Biophysics and senior author of the paper. “But our new algorithm lets us sweep through these millions of lines of genetic code and pick up even the faintest signals, resulting in a much more complete picture what DNA encodes.”

A few years ago, the two labs--Mann and Bussemaker--developed a genetic sequencing method called SELEX-seq to systematically characterize all Hox binding sites. Hox genes are known as the drivers of some of the body's earliest and most critical aspects of growth and differentiation. Still, SELEX-seq had limitations: It required the same DNA fragment to be sequenced over and over again. With each new round, more pieces of the puzzle were revealed, but information about those critical low-affinity binding sites remained hidden.

Faculty

Barry Honig

Director, Center for Computational Biology & Bioinformatics and Investigator, Howard Hughes Medical Institute
Director, Center for Computational Biology & Bioinformatics and Investigator, Howard Hughes Medical Institute