Navigation Links
Sex chromosome shocker: The 'female' X a key contributor to sperm production
Date:7/21/2013

CAMBRIDGE, Mass. -- Painstaking new analysis of the genetic sequence of the X chromosomelong perceived as the "female" counterpart to the male-associated Y chromosomereveals that large portions of the X have evolved to play a specialized role in sperm production.

This surprising finding, reported by Whitehead Institute scientists in a paper published online this week in the journal Nature Genetics, is paired with another unexpected outcome: despite its reputation as the most stable chromosome of the genome, the X has actually been undergoing relatively swift change. Taken together, these results suggest that it's time to reexamine the biological and medical importance of the X chromosome.

"We view this as the double life of the X chromosome," says Whitehead Institute Director David Page, whose lab conducted this latest research.

"The X is the most famous, most intensely studied chromosome in all of human genetics. And the story of the X has been the story of X-linked recessive diseases, such as color blindness, hemophilia, and Duchenne's muscular dystrophy," Page adds. "But there's another side to the X, a side that is rapidly evolving and seems to be attuned to the reproductive needs of males."

Page's lab, best known for its pioneering investigations of the Y chromosome, embarked on a rigorous comparison of the mouse and human X chromosomes, in part to test the longstanding biological tenet that the gene content of X chromosomes is conserved and shared across mammals. However, to render such a comparison valid, the lab had to upgrade the human X reference sequence, which was originally assembled as a mosaic of sequences from the X chromosomes of at least 16 people. This composite left the reference with errors and gaps that fail to capture so-called ampliconic regions containing segments of nucleotides that are virtually identical. Such near-complete identity prevents recognition of tiny but important differences.

To set the sequence straight, the lab turned to the unique sequencing method Page had developed with collaborators at Washington University in St. Louis to help navigate the structural complexities of the Y chromosome. As Page reported roughly a decade ago, the Y contains several regions of large palindromesareas of mirror-imaged genetic sequences. Such regions defy elucidation via conventional sequencing approaches, which simply cannot detect extremely subtle genetic differences found hidden among the "mirrors." In response, Page and colleagues devised what is known as SHIMS (single-haplotype iterative mapping and sequencing) to establish a definitive reference DNA sequence of the Y chromosome.

Using SHIMS, the lab greatly improved the human X reference sequence, accurately assembling three large amplicons, identifying previously unknown palindromes, and ultimately shortening the entire length of the sequence by eliminating four major gaps. These important updates will now be incorporated into the reference sequence of the human X for use by the greater scientific community.

Upgraded reference in hand, the lab discovered that, as might have been expected, the mouse and human X chromosomes have nearly 95% of their X-linked, single-copy genes in common. Almost all of these genes are expressed in both sexes. Strikingly, however, the lab identified approximately 340 genes that are not shared between the two species. Fittingly, most of these genes reside in ampliconic regions of the X and appear to have been acquired independently during the 80 million years since mouse and human diverged from a common ancestor. Expression analyses revealed that these genes are active almost exclusively in testicular germ cells, where, at a minimum, they likely contribute to sperm production. Further exploration of these X-ampliconic regions and their associated genes is warranted.

"This is a collection of genes that has largely eluded medical geneticists," says Jacob Mueller, a postdoctoral researcher in Page's lab and first author of the Nature Genetics paper. "None of these genes has been associated with a Mendellian trait. Now that we're confident of the assembly and gene content of these highly repetitive regions on the X chromosome, we can start to dissect their biological significance."

Adds Page: "These genes are more likely to have roles in diseases that are related to reproduction, infertility, perhaps even testis cancer. There's a whole other book to be written about this aspect of the X."


'/>"/>

Contact: Matt Fearer
fearer@wi.mit.edu
617-452-4630
Whitehead Institute for Biomedical Research
Source:Eurekalert

Related biology news :

1. New therapy for fragile X chromosome syndrome discovered
2. Clues to chromosome crossovers
3. A closer look at chromosomes
4. NYU biologists identify proteins vital to chromosome segregation
5. Chromosome anchors organize DNA during cell division
6. From Mediterranean coasts to Tatra Mountains and beyond: Plant chromosome number variation
7. Extra chromosome 21 removed from Down syndrome cell line
8. Western aspen trees commonly carry extra set of chromosomes
9. Study of fruit fly chromosomes improves understanding of evolution and fertility
10. Men can rest easy - sex chromosomes are here to stay
11. Discovery reveals chromosomes organize into yarns
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/20/2016)... MINNETONKA, Minn. , Jan. 20, 2016   ... that supports the entire spectrum of clinical research, is ... in 2015. MedNet,s significant achievements are the result of ... of) iMedNet eClinical , it,s comprehensive, ... --> --> Key MedNet growth ...
(Date:1/15/2016)... , Jan. 15, 2016 Recent publicized ... small to find new ways to ensure data security ... iOS and Android that ties ... biometrics, transforming it into a hardware authorization token. Customer ... swipe their fingerprint on their KodeKey enabled device to ...
(Date:1/11/2016)... Jan. 11, 2016 Synaptics Incorporated (NASDAQ: ... today announced that its ClearPad ® TouchView ™ ... won two separate categories in the 8 th ... Best Technology Breakthrough. The Synaptics ® TDDI solution ... supply chain, thinner devices, brighter displays and borderless designs. ...
Breaking Biology News(10 mins):
(Date:2/12/2016)... SAN DIEGO , Feb. 12, 2016 Biocom, ... life science community, took a group of San ... as part of its 2016 Precision Medicine Advocacy Fly-In. ... at the Food and Drug Administration (FDA), the Centers for ... (NIH), as well as San Diego U.S. Representatives Susan ...
(Date:2/12/2016)... MedGenome,s Commitment Will Help ... of Complex Diseases Such as Cancer, Metabolic Disorders, ... --> --> MedGenome, the market ... leading provider of genomics research services globally, today ... GenomeAsia 100K consortium as a founding member. ...
(Date:2/11/2016)... Germany and GERMANTOWN, Maryland ... QGEN ; Frankfurt Prime Standard: QIA) today announced the ... Panels for gene expression profiling, expanding QIAGEN,s portfolio of ... panels enable researchers to select from over 20,000 human ... discover interactions between genes, cellular phenotypes and disease processes. ...
(Date:2/11/2016)... ... February 11, 2016 , ... ... delivering cutting-edge information focused on the development and manufacture of biopharmaceuticals and ... premier sponsor of the 2016 BioProcess International Awards – Recognizing Excellence in ...
Breaking Biology Technology: