Researchers writing in BioMed Central's open access Journal of Biology have shown that expression in tissues with a limited number of specialized cell types is strongly conserved, even between the mammalian and non-mammalian vertebrates.
Timothy Hughes from the University of Toronto, Canada, worked with a team of researchers to investigate evolutionary alterations in gene regulation in the five different vertebrates. They found that although the specialized DNA sequences that regulate the expression of the genes seem to have changed beyond recognition over the hundreds of millions of years since the clades parted evolutionary company, the actual patterns of gene expression remain closely conserved. According to Hughes, "There are clearly strong evolutionary constraints on tissue-specific gene expression. Many genes show conserved human/fish expression despite having almost no nonexonic conserved primary sequence".
The authors studied 3074 genes that were present as a single unambiguous copy in each of the five genomes. The similar expression profiles they uncovered suggest the existence of a basic ancestral pattern of expression in each tissue, the so-called 'inner fish'.
The strongest similarities were seen in brain tissue. Hughes said, "This relatively low divergence of gene expression in brain supports the hypothesis that neurons participate in more functional interactions than cells in other tissues - imposing constraints on the degree of alteration that can be tolerated". Genes expressed in tissues subject to greater environmental influence (such as intestine, stomach and spleen) may be more likely to take on new roles and diverge in expression as a means of adaptation.
Although this study only investigated vertebrates, these expression profiles may go much further back into our past. The authors conclude, "It is likely that the conservation of gene expression extends beyond the base of vertebrates, coexpression of neuronal genes, for example, has been observed as far as nematodes".
biomedcentral/
The report provides case studies in which DECIPHER played a pivotal role. In one example a four-year-old girl with symptoms of developmental delay and poor eye contact had a novel genetic finding and remained without a clear diagnosis. However, two new cases with similar structural variants were submitted to the database one year later, to provide the elusive diagnosis. The case studies exemplify increasing value of the database as clinicians add case information.
"DECIPHER is particularly useful when we look at patients with developmental delay, learning disability, dysmorphic features or congenital abnormalities, where, using genomic array technology, we can assign a diagnosis in 15 per cent of previously undiagnosed cases," explains Helen Firth, Consultant Clinical Geneticist at Addenbrookes Hospital and lead author on the study. "This improvement is dependent on a fantastic level of collaboration. More than 2000 patient cases have been contributed to the DECIPHER database since its inception: its diagnostic power strengthens as new cases are added"
DECIPHER is built upon the Ensembl genome browser. It is the only open-access, web-based interactive database of its type, although data from other databases are available. The report's authors suggest that while combination of all data in one resource would be ideal, providing access to the data in one genome browser is a realistic and practical method of harnessing the combined power of the datasets.
Sharing data between researchers is increasingly important. As the role of CNVs in human disease is better understood, so resources such as DECIPHER will gain momentum that will drive significant health benefits and improvements to genetic counselling.
sanger.ac/