More genes that turn on just one copy than earlier believed

November 16th, 2007 - 4:23 pm ICT by admin  

London, Nov 16 (ANI): A new study has challenged the long thought belief for human genes that sequences from both paternal and maternal chromosomes are equally expressed within a cell by finding that hundreds of our genes turn on just one copy, rather than both.

Researchers at the Harvard University in Cambridge, Massachusetts say that this mechanism may allow cells to generate phenotypic diversity from a common genome.

It had been thought that there are only a handful of situations in which just one of a pair of gene copies is used. But a new screen of 4,000 human genes has uncovered 371 that sometimes play favourites, suggesting that this phenomenon is far more omnipresent than had been thought.

What weve shown violates general rules about what we think about genes: if a gene is turned on you express both the maternal and paternal copy, Nature quoted Andrew Chess, a biologist at Harvard, who led the study along with colleague Alexander Gimelbrant, as saying.

This kind of selective gene expression could create an additional source of variation between people, even when some of their genes are identical, he added.

Researchers have long known that some cells express just one version of certain genes, but this is for a specific purpose. Females have two X chromosomes but always shut down one copy, for example, to prevent making a double dose of some gene products. Immune cells designed to recognize the fingerprint of a specific disease turn off one set of immunoglobulin genes to optimize their specialist behaviour.

And during development, embryos chemically flag one parents version of a set of known genes for silencing. This handful of instances accounts for hundreds of genes known to turn off a copy in a controlled way.

To track more genes that behave similarly, Chess and Gimelbrant planted single human immune cells in dishes, and let the cells multiply. They examined the millions of cell copies using a gene chip to differentiate between the maternal and paternal version of messenger RNA (mRNA) produced by 3,939 genes.

The team found that that about 9 percent of the genes sometimes turned on just one copy.

Even though the cells were all genetically identical, some turned on maternal versions, some paternal, and others activated both.

“Even identical twins would make different choices,” said Gimelbrant.

The team observed a similar pattern in a much smaller division of genes that they looked at from specimens of donated human placenta and white blood cells.

This is not something weird that happens only in cell culture, says Chess.

Chess said that these differences could potentially help an organism to control gene expression and affect disease risk. Higher expression of a gene called APP is linked to early onset of Alzheimers disease, for example.

Chesss team found that cells in which just one copy of APP was turned on made about half as much mRNA as the cells with both copies turned on. At this point, the connection to Alzheimers remains speculative, he says.

The random gene inactivation that Chess’s team has found could be a spillover from more controlled forms of silencing, such as shutting down an X chromosome, says Huntington Willard, a geneticist at Duke University in Durham, North Carolina.

The study is published in Science. (ANI)

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