The twin revolutions of genomics and informatics are changing the face of biomedical research. Every day all over the world, millions of genetic sequences — from disease-related genes to complete genomes of plants, animals, bacteria and viruses — are resolved, identified and dissected.
One of the most fascinating applications of the available information stemming from different organisms is the possibility to identify novel disease-related genes and predict their biological functions. The technique is simple and based on the fact that genes that work together or those that play an important role in biology will be present together in organisms that need them. Conversely, genes connected to a particular function like vision will disappear from species that have lost the power of sight, and may therefore be identified by a comparison to the genes in normal animals.
One example of a known mutation which increases the likelihood of developing breast and ovarian cancers is in the BRCA1 gene. Interest in this gene was highlighted when, in 2013, Angelina Jolie, having discovered that she had inherited the dangerous mutation from her mother who died of cancer aged 56, decided to undergo a preventative double mastectomy. However in the majority of cases, both for breast cancer and other genetically transmitted diseases, the identity of the gene responsible is unknown.
By using the methods of genetic analysis, researchers can now identify genes within the same network as the BRCA1 gene, or other associations of genes, simply by scanning the evolutionary profiles of tens of organisms with a single click. The number of organisms that can be scanned in this way is anticipated to increase to hundreds in the near future.
An interesting example of a gene that could be identified using this phylogenetic profiling approach is the so-called “Vampire’s Disease,” more professionally termed porphyria. Representing a family of genetic diseases characterized by abdominal pain, sensitivity to sunlight, purple urine, and psychotic episodes, porphyria probably forms the basis for the prevalent myths of vampires. These diseases are rare, but there is evidence for hereditary porphyria in European royal families, and it may have been responsible for the madness of King George III as well as for the psychotic behavior of the painter Vincent Van Gogh, misdiagnosed as a depressive schizophrenic. With one click, it is possible to identify essentially all the genes known to be associated with porphyria as well as other genes that, based on their phylogenetic profile, are very likely to be involved.
Citation: Ilyas R. Sadreyev, Fei Ji, Emiliano Cohen, Gary Ruvkun, and Yuval Tabach, “PhyloGene server for identification and visualization of coevolving proteins using normalized phylogenetic profiles”, Nucleic Acids Research doi: 10.1093/nar/gkv452