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University Of Chicago Study Overturns Conclusion Of Historic Human Genome Data

Date:
January 23, 2004
Source:
University Of Chicago Medical Center
Summary:
Researchers at the University of Chicago have discovered there is extensive gene "traffic" on the mammalian X chromosome and overturn a conventional theory about how the genes evolved on the sex chromosome.

Researchers at the University of Chicago have discovered there is extensive gene "traffic" on the mammalian X chromosome and overturn a conventional theory about how the genes evolved on the sex chromosome.

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The study, published in the Jan. 23, 2004, issue of Science, shows that an excess of genes on the X chromosome "jump" to a non-sex chromosome, or autosome, during germline cell division. This finding contradicts the historic human genome project paper published in Science Feb. 16, 2001, that claimed the X chromosome had an average rate of traffic similar to all autosomes. The discovery also torpedoes the conventional theory that the X chromosome is the 'hot bed' for sex-related genes.

"That's just not true," said Manyuan Long, the associate professor of ecology and evolution who led the study.

Since the X chromosome becomes inactive – meaning it shuts down – during male meiosis, the U. Chicago researchers suggest the male-expressed genes must flee the X before this phenomenon takes place.

Long and his colleagues propose that sexual antagonism may also cause this high traffic volume on the X. Since females have two X chromosomes and males have only one, the X is more likely to end up in a female. And if there is a beneficial gene mutation on the X, there is a higher chance that it would help the female, despite its affect on the man. The researchers suggest that the male-expressed genes leave the X for an autosome, where each gene would have the same share of the chromosome and therefore a better environment to carry out its function more effectively.

"An X-linked gene spends two-thirds of its time in females compared with one-half for an autosomal gene, thus the X chromosome becomes 'demasculinized,'" the researchers wrote in the paper.

The research team contends that either theory justifies male-expressed genes leaving the X chromosome, whether the X kicks them out or they merely jump ship before the X shuts down. "The two explanations are not mutually exclusive," Long said. "Either way, if [the male-expressed genes] remain on the X chromosome, they would not be able to do their job well. They have to leave in order to carry out their function."

Besides studying the human genome, the researchers also charted the gene traffic of the X chromosome, as well as its 19 autosomes, for the mouse and found the same basic pattern. Long's laboratory first discovered this pattern of X-derived autosomal genes that express in the testis using the fruit fly, work published in Genome Research in 2002. The latest study by his team confirms the pattern in two mammalian species.

"The most important result of the paper is the phenomenon itself," said J.J. Emerson, fourth year graduate student in Long's lab and one of the lead authors of the paper. "We can see very clearly that the X is an unusual case. Through the evolution of gene duplication, the X chromosome seems to have an excess of traffic."

Through various mechanisms, genes duplicate. The original copy can remain where it is and another version of it can be placed elsewhere in the genome. This type of gene duplication is one of the ways organisms diversify. "You can duplicate a gene used for one function, tweak it just a little bit, and you can have a totally new function," Emerson said. "When you need new functions, gene duplication provides those new functions, and it's a beautiful mechanism for giving biological novelty."

The scientists looked at retroposed genes -- those genes that are copied by being reinserted randomly into the genome -- simply because scientists can map the direction of those genes (whether it left or joined the chromosome). The team looked at the "expected levels of traffic" by plotting pseudo genes -- those genes that lose their function after being duplicated and which natural selection ignores.

The researchers compared the rate of gene traffic on the X to all of the autosomes and found the X chromosome exports four times as many genes than the average autosome and imports 3.5 times as many. They did not look at the traffic rate of the Y chromosome. "It's such a small chromosome that any excess or decrease is miniscule-" Emerson said. They found that 77 percent of the genes leaving the X chromosome have testis expression, compared to 44 percent of genes that jump from autosome to autosome.

The researchers noted that this Darwinian process has evolved slowly since both mouse and humans share the same excess traffic characteristics on the X chromosome. It was therefore present prior to the mouse-human split.

The study also shows that although approximately 71 percent of those genes leaving the X chromosome are to be expressed in a male germline cell, only about 14 percent of the genes being imported to the X are female expressed.

"So the old idea that the X chromosome is a major contributor of sexual genes is also not true," Long said. "The X chromosome is not the 'hot bed' of sex-related genes that was once thought."

The researchers plan to take a closer look at the excess traffic, tracking the exported genes as well as their expression. They also are trying to locate where the majority of female-expressed genes originate.

Long recently received two research grants: a CAREER Award from the National Science Foundation providing nearly a million dollars over five years and grant of more than one million dollars from the National Institutes of Health. Both the NSF and the NIH, as well as the Packard Foundation, supported this research.

Additional authors include former U. Chicago postdocs Esther Betran, PhD, now of the University of Texas at Arlington, and Henrik Kaessmann, PhD, (the other lead author of the paper) now of the University of Lausanne in Switzerland.


Story Source:

The above story is based on materials provided by University Of Chicago Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of Chicago Medical Center. "University Of Chicago Study Overturns Conclusion Of Historic Human Genome Data." ScienceDaily. ScienceDaily, 23 January 2004. <www.sciencedaily.com/releases/2004/01/040123004427.htm>.
University Of Chicago Medical Center. (2004, January 23). University Of Chicago Study Overturns Conclusion Of Historic Human Genome Data. ScienceDaily. Retrieved October 31, 2014 from www.sciencedaily.com/releases/2004/01/040123004427.htm
University Of Chicago Medical Center. "University Of Chicago Study Overturns Conclusion Of Historic Human Genome Data." ScienceDaily. www.sciencedaily.com/releases/2004/01/040123004427.htm (accessed October 31, 2014).

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