Researchers discover use of novel mechanism preserves Y chromosome genes

June 18, 2003

BETHESDA, Md., June 18, 2003 - A detailed analysis of the just-completed sequence of the human Y chromosome - the chromosome that distinguishes males from females - has uncovered a novel mechanism by which it maintains its genetic integrity. The study is published in the current issue of Nature.

All other chromosomes occur in pairs and preserve genetic integrity by exchanging information with matching genes on the homologous chromosome, a process called "crossing over." But the Y chromosome lacks that option, being the only chromosome that is unpaired. Instead, the Y appears to exchange genes between the two arms that make up the chromosome itself.

This phenomenon, called gene conversion - the non-reciprocal transfer of genetic information from one DNA molecule to another -- has been previously observed on a small scale over long evolutionary timescales between repeated sequences on the same chromosome, but not at the dramatic frequency apparently employed by the Y chromosome.

A research team, led by David C. Page, M.D., a Howard Hughes Medical Institute investigator at the Whitehead Institute for Biomedical Research in Cambridge, Mass.; Richard K. Wilson, Ph.D., director of the Genome Sequencing Center at Washington University School of Medicine in St. Louis; and Robert H. Waterston, M.D., Ph.D., formerly of Washington University's sequencing center and now at the University of Washington, Seattle, discovered that many of the sequences of chemical units -- called bases or base pairs -- that carry genetic information on the Y chromosome are arranged as palindromes. Palindromes are phrases or sentences that read the same backward or forward, such as "Madam, I'm Adam."

In the case of the Y, the palindromes are not just "junk" DNA; these strings of bases contain functioning genes important for male fertility. The team found that most of the sequence pairs are greater than 99.97 percent identical. The extensive use of gene conversion appears to play a role in the ability of the Y chromosome to edit out genetic mistakes and maintain the integrity of the relatively few genes it carries.

"This analysis of the Y chromosome could not have been done without the highly accurate sequence data produced by the Human Genome Project and made freely available to researchers everywhere in the world," said Francis S. Collins, M.D., Ph.D., director of the National Human Genome Research Institute (NHGRI), which, along with the U.S. Department of Energy, led the Human Genome Project in the United States. "Unless the human sequence had been finished to the highest level of accuracy - less than one mistake in every 10,000 bases, the Y chromosome researchers would not have been able to identify the Y's unusual genetic structure and the novel mechanism for maintaining its integrity. Of all the human chromosomes, this was probably the most challenging to assemble correctly, and could never have been done without the painstaking map-based approach adopted by the International Human Genome Sequencing Consortium."

In a separate paper in the same issue of Nature, the team confirmed its findings by comparing similar regions of the Y chromosome in humans to the Y chromosomes of chimpanzees, bonobos (the pygmy chimpanzee) and gorillas. The comparison demonstrated that the same phenomenon of gene conversion appeared to be at work more than 5 million years ago, when humans and the non-human primates diverged from each other.

"The comparison between human and non-human primate chromosomes confirming the finding shows the power of comparative genomics," Dr. Collins said. "Without the ability to compare the genetic material across species, it would have been difficult for the team to test their hypothesis." NHGRI now funds a number of genome sequencing projects on model organisms, including the dog, the chimp, the chicken and the honeybee. The mouse, rat and fruit fly sequencing projects are essentially completed - except, ironically, for the Y chromosome of each of those species, which are still under construction.

The sequencing work on the Y chromosome was carried out at the Genome Sequencing Center at the Washington University School of Medicine as part of the Human Genome Project, which receives substantial funding from NHGRI. The Human Genome Project officially began in October 1990 and was completed in April 2003; sequencing the rough draft of the human genome sequence cost an estimated $300 million. The entire project, including genetic mapping, technology development, the study of model organisms, and the ethical, legal and social implications (ELSI) program was initially projected to take 15 years, but was completed more than two years early at a cost that was $400 million less than expected.

The initial analysis of the draft human genome sequence was published in February 2001. With the completion of the project, researchers plan to publish a separate analysis on each completed chromosome over the next year or so.
-end-
NHGRI is one of the 27 institutes and centers at the National Institutes of Health, an agency of the Department of Health and Human Services. Additional information about NHGRI can be found at its Web site, http://www.genome.gov.

NIH/National Human Genome Research Institute

Related Chromosomes Articles from Brightsurf:

Cancer's dangerous renovations to our chromosomes revealed
Cancer remodels the architecture of our chromosomes so the disease can take hold and spread, new research reveals.

Y chromosomes of Neandertals and Denisovans now sequenced
An international research team led by Martin Petr and Janet Kelso of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, has determined Y chromosome sequences of three Neandertals and two Denisovans.

Female chromosomes offer resilience to Alzheimer's
Women live longer than men with Alzheimer's because their sex chromosomes give them genetic protection from the ravages of the disease.

New protein complex gets chromosomes sorted
Researchers from the University of Tsukuba have identified a novel protein complex that regulates Aurora B localization to ensure that chromosomes are correctly separated during cell division.

Breaking up is hard to do (especially for sex chromosomes)
A team of scientists at the Sloan Kettering Institute has discovered how the X and Y chromosomes find one another, break, and recombine during meiosis even though they have little in common.

Exchange of arms between chromosomes using molecular scissors
The CRISPR/Cas molecular scissors work like a fine surgical instrument and can be used to modify genetic information in plants.

How small chromosomes compete with big ones for a cell's attention
Scientists at the Sloan Kettering Institute have solved the puzzle of how small chromosomes ensure that they aren't skipped over during meiosis, the process that makes sperm and egg.

GPS for chromosomes: Reorganization of the genome during development
The spatial arrangement of genetic material within the cell nucleus plays an important role in the development of an organism.

Extra chromosomes in cancers can be good or bad
Extra copies of chromosomes are typical in cancerous tumor cells, but researchers taking a closer look find that some extra copies promote cancer growth while others actually inhibit cancer metastasis.

X marks the spot: recombination in structurally distinct chromosomes
A recent study from the laboratory of Stowers Investigator Scott Hawley, PhD, has revealed more details about how the synaptonemal complex performs its job, including some surprising subtleties in function.

Read More: Chromosomes News and Chromosomes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.