Study confirms males and females have at least one thing in common: Upregulating X

October 24, 2011

In a study published today in the journal Nature Genetics, a group of scientists including UNC biologist Jason Lieb, PhD, present experiments supporting a longstanding hypothesis that explains how males can survive with only one copy of the X chromosome. The finding provides clarity to a hotly debated topic in science and provides biologists with more information to interpret experiments involving genetic measurements in males and females.

"The issue is important because many diseases are tied to a defect in a within the cell," said Lieb, who is also a member of UNC Lineberger Comprehensive Cancer Center.

Women have two X chromosomes, while men have one X and one Y. The lack of a 'back up' copy of the X chromosome in males contributes to many disorders that have long been observed to occur more often in males, such as , Duchene muscular dystrophy, and certain types of color blindness. Having only one copy of X and two copies of every other chromosome also creates a more fundamental problem – with any other chromosome, the gene number imbalance resulting from having only one copy would be lethal. How can males survive with only one X?

have been debating how organisms and cells manage the imbalance between X and other chromosomes for years, with the dominant theory being that both sexes up-regulate the expression of X-linked genes, essentially doubling their expression to "2X" in males and "4X" in females. Then, to correct the imbalance that now appears in females (since they have the equivalent of "4" Xs now and 2 of every other chromosome), females then 'turn off' one of the hyperactive X chromosomes, resulting in a balanced "2X" expression of those genes across both sexes.

The advent of new technology based on RNA sequencing and proteomic analysis has given scientists more accurate ways to measure gene expression, and some results published in the last few years have not supported the idea that X chromosomes up-regulate.

Lieb and his colleagues re-analyzed data used in previous analyses, along with new data from humans, mice, roundworms, and fruit flies and found more evidence that the up-regulation is correct – but with some interesting twists across species. In mammals – humans and mice – both up-regulate X chromosome gene expression and females then equalize expression by turning off the one X chromosome. In roundworms (C. elegans) the both female X stay active, but the genes on both Xs are down-regulated by half to compensate in the females. In fruit files (Drosophilia melanogaster), increase the expression of genes, with no upregulation of X in females.

"There are several ways to get the same result and we are seeing how the dosage-balancing mechanism works in different species," says Lieb. "We also found that not all X-linked genes are dosage compensated to the same degree– adding another layer of complexity for scientists who study gene regulation."

Related Stories

Recommended for you

New class of RNA tumor suppressors identified

November 23, 2015

A pair of RNA molecules originally thought to be no more than cellular housekeepers are deleted in over a quarter of common human cancers, according to researchers at the Stanford University School of Medicine. Breast cancer ...

Batten disease may benefit from gene therapy

November 11, 2015

In a study of dogs, scientists showed that a new way to deliver replacement genes may be effective at slowing the development of childhood Batten disease, a rare and fatal neurological disorder. The key may be to inject viruses ...

Molecular clocks control mutation rate in human cells

November 9, 2015

Every cell in the human body contains a copy of the human genome. Through the course of a lifetime all cells are thought to acquire mutations in their genomes. Some of the mutational processes generating these mutations do ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Oct 24, 2011
They "up-regulate" indeed.
Now, if we could see when and how the up-regulation is done, we could catch genetically-based disease in the ACT!
Further, with all the advances being made in stem cells, biotech, nanotech, and genetics and pharmacology, increasingly one can see the need for a unified repository of this data. We need a way to keep the left hand knowing what the right hand has done. Somewhere, all new knowledge can be 'pieced' together so we don't miss the chance to solve or cure something because we did not 'put-it-all-together'.
I just get the feeling we are closing in on something MAJOR and I don't want us to miss it.
I think we need a science-only, make-it-real, DARPA, or data repository.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.