For a long time, gene expression seemed fairly straightforward. We knew that when cellular machinery arrives at the start site of an active gene, the gene sequence is transcribed into a messenger RNA molecule, which is then modified before ribosomes translate it into a protein. But research has shown that sometimes, there is 'misbehavior' in gene expression. For example, gene transcripts may not always start or end where they should. And new research has shown that occasionally, genes are active when they should be turned off, even in healthy people.
A new study reported in the American Journal of Human Genetics has described several situations in which inactive genes are expressed anyway. This study determined that in a healthy group of people, misexpression is somewhat rare at the level of single genes, but can occur in over half of genes that should not be expressed. This work may help shed new light on how some complex disorders that can involve many genes may arise.
There are around 20,000 genes in the human genome that code for protein. The identity of specific cells, whether they are in the heart, brain, or other parts of the body, largely depend on the types of genes that are expressed in cells. Thus, gene expression has to be carefully controlled or problems can arise. There are a few rare disorders that are known to involve gene misexpression, but this is one of the first to investigate the phenomenon in healthy people.
Blood samples from over 4,500 healthy people were collected, and the mRNA in these samples was analyzed. Since active genes are expressed as mRNA, the researchers could determine which genes were being expressed. While there was only misexpression in 0.07 percent of genes, there was evidence of misexpression in almost every sample, (96 percent). Additional work indicated that most of the misexpression was due to structural changes in DNA, which can affect which areas of the genome are available to the cellular machinery that expresses genes.
These results have suggested that while many healthy people do misexpress some genes, it happens at low levels and probably does not have a major impact on health. However, there may be some cases in which misexpressed genes are exerting a serious influence.
"Interestingly, while over half of genes occasionally misexpress, we find certain critical genes, particularly those governing development, rarely make such mistakes. This suggests that when these essential genes do misexpress, the consequences for health and disease are likely to be more severe," noted study co-author Dr. Katie Burnham of the Wellcome Sanger Institute.
Sources: Wellcome Trust Sanger Institute, American Journal of Human Genetics