EMBL scientists discern key gene expression patterns in the human genome


Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have pinpointed key activities in the human genome that are important for the understanding of health and disease. The findings, published in the journal PNAS, highlight finely tuned, crucial events within a seemingly chaotic landscape.

When the first human genome was sequenced, many were surprised at how few genes we have: around 21,000, no more than a worm has. How can so few genes give rise to the complexity of the human body, with its hundreds of cell types?  One reason might be that our genes are broken up into parts (called exons), which are put together in various patterns to form different messages. In this manner, the same gene could issue different instructions in different organs. But the process is delicate, and it is difficult to tell which messages are important.

To find out, EMBL scientist Wolfgang Huber and his colleagues set out to determine how many of these exon patterns are important enough to have been conserved over the course of evolution. Using sequencing data from the University of Lausanne, they examined how exons are used in different human organs and compared their findings with data from five other primate species.

“We wanted to know which messages were important and which are noise,” says Wolfgang Huber. “People have wondered about this question for a long time, but we’ve only recently had the right technology to nail it down.”

The team examined five different organs to find exons whose usage differed between the organs. For these, they tested whether the pattern of usage was consistent amongst the primate species and, therefore, likely to be important for an organ’s function. Many of the usage patterns seemed to occur randomly. However, in 1643 genes, they found organ-specific messages that were conserved throughout evolution.

“We looked at gene expression data from several related species, and developed a novel statistical tool to analyse it,” said bioinformatician Alejandro Reyes of EMBL. “It was exciting to see a clear picture of what is going on with these exons in the different organs, and to start making sense of it all.”

“These patterns we found are important enough that they have been preserved for 25 millions years,” explains Wolfgang Huber. “What we’ve done, effectively, is to separate the wheat from the chaff – we can now explore why the presence of a particular exon is useful for, say, brain cells but not for muscle cells.”

The findings establish that specific exon activities are important to the functioning of human organs, and provide a rich resource for the study of genetics relating to human health and disease. The next step for the team is to study more tissues, drawing on large-scale studies of human variation and disease such as the Genotype-Tissue Express (GTEx) and International Cancer Genome projects.

Source Article

Reyes et al. (2013) Drift and conservation of differential exon usage across tissues in primate species. Published online in PNAS on DOI: 10.1073/pnas.1307202110