Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Learning About Sex From an Elegant Worm

19.12.2005


C. elegans is less than a millimeter in length and completely transparent. In the hermaphrodite, sex-cell division takes place within the tubelike arms of the gonad. As cell nuclei move through them, every stage of meiosis can be observed under the microscope.


Three Major Papers Advance Understanding of Meiosis in C. elegans

Most cells in the body contain two copies of every chromosome, one from each parent. Sex involves gently scrambling the genetic material of the chromosomes to produce variations within each species, creating individuals variously equipped to meet life’s challenges. The secret of sex is meiosis, a specialized kind of cell division in which a cell replicates and then divides twice (not just once, as nonsex cells do), resulting in sperm or eggs with just one set of chromosomes each.

Now researchers at Lawrence Berkeley National Laboratory, the University of California at Berkeley, and their collaborators at other institutions have discovered new details of the mechanisms employed by a remarkable animal, the diminutive roundworm Caenorhabditis elegans, to ensure that the chromosomes of its sperm and eggs have been matched and recombined accurately during meiosis. Their discoveries hold promise for understanding human infertility.



Led by Abby Dernburg of Berkeley Lab’s Life Sciences Division, who is also an assistant professor of cell and developmental biology at UC Berkeley, the researchers offer new insight into meiosis in C. elegans in two papers published in the 16 December, 2005 issue of Cell, and in a related paper published in the 9 December issue of Science.

C. elegans is a tiny worm less than a millimeter in length and completely transparent. Its reproductive organs make up over half its cells, so by labeling cells with fluorescent dyes and viewing them under a visible-light microscope, observing meiosis is straightforward.

C. elegans has other features that make it particularly useful for studying reproduction. There are two sexes, male and hermaphrodite, with hermaphrodites far more numerous. There are five pairs of nonsex chromosomes and a single sex chromosome, the X. An animal that inherits two Xs becomes a hermaphrodite (XX); a single X chromosome (X0) results in a male.

"In the hermaphrodite, meiosis takes place over a three-day period within the arms of the gonad, tubelike chambers that terminate at the uterus," Dernburg explains. "As cell nuclei progress through meiosis, they also move spatially within this structure, ultimately ending up as either eggs or sperm; the hermaphrodite mixes these together to fertilize new embryos. So the entire temporal progression of meiosis can be observed in a gradient from early to late stages."

Pairing centers and how they work

An essential step early in meiosis is chromosome pairing: two matching chromosomes, or homologs, must contact and recognize each other and stay together during the recombination process, while sequences of DNA on one chromosome trade places with corresponding sequences on the other (which may have different versions of the same genes).

Homologous chromosomes remain locked together until they are pulled apart into opposite daughter cells. What mechanisms allow the chromosomes to recognize appropriate partners and reject inappropriate ones are among the fundamental questions addressed in the two 16 December Cell papers.

Regions called Pairing Centers, or PCs, are found near one end of each C. elegans chromosome. In one of the Cell papers, Dernburg and her colleagues, including Amy MacQueen of Stanford University (now at Yale), Carolyn Phillips of UC Berkeley, Needhi Bhalla of UC Berkeley and Berkeley Lab, Pinky Weiser of Berkeley Lab, and Anne Villeneuve of Stanford, establish that Pairing Centers perform two separate, critical functions during meiosis.

First, PCs facilitate chromosome pairing by stabilizing a previously-unrecognized intermediate in the pairing process. Second, they act to promote the "zipping together" of the chromosomes, called synapsis, in which a protein polymer forms along the chromosomes to hold them together during recombination. Normally these processes work together to ensure that chromosomes are correctly matched and recombined.

PCs aren’t the only sites that promote pairing, the researchers realized; recombination can occur even when two chromosomes are not a perfect match. Yet Pairing Centers seem to provide a proofreading mechanism that strongly discourages inappropriate partnerships. This discrimination is important to minimize the likelihood of genetic abnormalities such as chromosome rearrangments or missegregation events, which in humans give rise to birth defects like Down syndrome.

"How can we explain the fact that PCs strongly contribute to the synapsis of matched chromosomes without being strictly required for this process?" Dernburg asks. She and her colleagues believe that, normally, PCs act to hold a pair of chromosomes together long enough for the quality of their match to be assessed (through chemical bonds or other molecular means, now under investigation). Those that make a good match then undergo synapsis.

For the X chromosome, at least, Dernburg and her colleagues have identified a key factor responsible for the Pairing Center’s functions. In the second paper in Cell, she and Carolyn Phillips and Chihunt Wong of UC Berkeley (Wong is now at the Salk Institute for Biological Studies); Needhi Bhalla, Peter Carlton, and Pinky Weiser of Berkeley Lab; and Philip Meneely of Haverford College describe how a gene called him-8 (the name derives from "high incidence of males") is essential for pairing and synapsis of the X chromosome.

The gene, which is not on the X chromosome but on one of the nonsex chromosomes, codes for a protein, HIM-8, with a well-known structure called a zinc finger, which usually recognizes and binds to a specific sequence of DNA. HIM-8 appears to tether the matched chromosomes to the cell’s nuclear envelope, the layer of membranes and associated proteins that encloses the DNA in all eukaryotic cells. Just why tethering to the nuclear envelope is essential for stable pairing is now under investigation. What’s clear is that without it, pairing of X chromosomes in C. elegans cannot occur.

Versatile Pairing Centers do even more

These studies inspired a complementary set of experiments by Needhi Bhalla, a postdoctoral fellow in the Dernburg group. Bhalla’s work has demonstrated the existence of a new checkpoint, or quality control mechanism, that operates during meiosis to eliminate defective nuclei if their chromosomes fail to pair or synapse. The new checkpoint specifically seems to detect unpaired Pairing Centers, revealing yet another essential role for these chromosome regions. Bhalla and Dernburg report their results in the 9 December issue of Science.

To guard against mistakes during meiosis, all sexually reproducing organisms employ checkpoints at which cell division may be halted and defective cells made to self-destruct through programmed cell death (apoptosis). In yeast, a checkpoint detects errors in chromosome matching, synapsis, and recombination. In mammals there may be two checkpoints, one that reacts to synaptic failure and another to DNA damaged during recombination. In both yeast and mice, however, the processes of synapsis and recombination are so intimately coupled that it is uncertain whether their checkpoints are triggered by failure of synapsis, errors in recombination, or both together.

In C. elegans the processes of recombination and synapsis can be uncoupled, unlike other organisms in which meiosis has been studied. Bhalla realized that the genetic mutations they were using to knock out the Pairing Centers of the X chromosome in C. elegans were excellent tools to investigate the worm’s meiotic checkpoints and learn how they worked.

"We had a mutation that knocked out the PC on the X chromosome," Bhalla says. "When the PCs on both chromosomes were missing, there was almost no synapsis. And because an unmatched X chromosome can result in eggs and sperm that are missing the X chromosome, the mutated hermaphrodites had many more male progeny than wild-type hermaphrodites would."

But where only one of the two X chromosomes was missing its PC, forty percent of the pairs did undergo synapsis. "The curious thing was, now only about six percent of the hermaphrodite’s self-progeny were males," she says. "That means that with just one PC, there was still significant failure of the X chromosomes to synapse but that a lot of the defective nuclei were somehow being eliminated."

Further genetic tests — including similar results when just the zinc-finger protein HIM-8 was eliminated from the X chromosome, instead of the entire region containing the PC — established that two meiotic checkpoints were at work in the worm. One, previously characterized, assessed DNA damage occurring during recombination. The newly discovered checkpoint employed the Pairing Center itself, and responded to the lack of synapsis even when the DNA-damage checkpoint was inactive.

Says Dernburg, "It used to be taken as a paradigm that both these checkpoint activities were interdependent. Needhi has demonstrated unambiguously that there is a separate checkpoint monitoring synapsis, and that checkpoint requires the PC."

One result of the study was to show that the synapsis checkpoint requires the activity of a checkpoint gene also found in yeast, suggesting that many organisms other than the humble worm may employ similar mechanisms to guard against synaptic failures during meiosis. In their report, Bhalla and Dernburg point to one promising area of further research, which will "likely shed light on the basis of human infertility, particularly in males, which has been linked to synaptic defects."

"Chromosome sites play dual roles to establish homologous synapsis during meiosis in C. elegans," by Amy J. MacQueen, Carolyn M. Phillips, Needhi Bhalla, Pinky Weiser, Anne M. Villeneuve, and Abby F. Dernburg, appears in the 16 December, 2005 issue of Cell. "HIM-8 binds to the X chromosome Pairing Center and mediates chromosome-specific meiotic synapsis," by Carolyn M. Phillips, Chihunt Wong, Needhi Bhalla, Peter M. Carlton, Pinky Weiser, Philip M. Meneely, and Abby F. Dernburg, appears in the 16 December, 2005 issue of Cell. "A conserved checkpoint monitors meiotic chromosome synapsis in Caenorhabditis elegans," by Needhi Bhalla and Abby F. Dernburg, appears in the 9 December, 2005 issue of Science.

Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California.

Paul Preuss | EurekAlert!
Further information:
http://www.lbl.gov/Science-Articles/Archive/LSD-worm-meiosis.html
http://www.lbl.gov

More articles from Life Sciences:

nachricht Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>