Printer Friendly

How worms' sex behavior can have a major impact on understanding human disease.

The "Golden Fleece Award" was established by the late Senator William Proxmire in 1975 to call attention to wasteful federal spending on useless and seemingly inane research. No doubt, enormous waste and corruption routinely emanate from Washington, DC. However, this and other efforts to expose such evil sometimes have the effect of trivializing basic scientific inquiry that has no obvious and immediate benefit to man. For example, a Golden Fleece was awarded to a study of the sex life of the screw-worm fly. After the senator's criticism of this $250,000 research project, the results were used to create sterile screw-worms that were released into the wild and eliminated this major cattle parasite from the US. This effort saved the US cattle industry about $20 billion.

Although it did not win a Golden Fleece Award, the more recent study of the mating behavior of the roundworm Caenorhabditis elegans seemed like another waste of time and money to some underinformed individuals. However, no one could have predicted that this X-rated worm research could have a profound impact on our understanding of an important and severe human disorder--autosomal dominant polycystic kidney disease (ADPKD)--and lead to new treatments for patients with this disorder.

ADPKD is the most common form of the genetic cystic kidney diseases; it affects more than 12 million patients worldwide and 600,000 in the USA. The disorder is characterized by the development of innumerable cysts in the kidneys and other organs, including the liver, and eventual dysfunction of the affected organs. Most patients with ADPKD will eventually develop kidney dysfunction and require dialysis or transplantation. Some succumb to ruptured cerebral aneurysms, which develop in about 10% of the patients. As genetic research progressed, the gene found to be mutated in this disease was identified and called pkd-1. (This gene accounts for about 80% of the adult form of this disease. The other 20% is caused by a different gene, pkd-2.) The protein product of the gene was identified and named polycystin. However, for some time, no one knew what this protein did or how its mutated state produced kidney problems.

Then some answers came from research into the sex life of the round worm C. elegans (Figure). This particular roundworm is a very popular and famous worm among many worm researchers (yes, there are many). C. elegans has certain characteristics that make it very attractive for scientific study. The roundworm is small, has two sexes--a hermaphrodite female and a male--rapidly reproduces in large numbers, can be frozen for an extended time (more than 10 years), and then when thawed returns to life! These features led Sydney Brenner to use this worm to study the genetic regulation of organ development and programmed cell death. In 1998, C. elegans became the first multicellular organism to have its genome completely sequenced. Then in 2002 Brenner shared the Nobel Prize in Medicine for his C. elegans work.


So, when Paul Sternberg and Maureen Barr, two scientists at the California Institute of Technology, were interested in studying the genetics of neural behavior, they decided to focus on C. elegans. They described the worm's stereotypical mating behaviors using light microscopy. (The worms are small, about 1 mm in length, and almost transparent.) First the male finds the hermaphrodite female using ciliated sensory neurons located in his head and tail. Then he attaches his tail to the female body and searches for the vulval opening and transfers the sperm. If unable to find the vulva, the worm continues to scan her body, turns at her head, and reinitiates the search. Upon extensive observations, these scientists noted that some worms could never find the vulva. They traced this defect to a genetic mutation and identified the specific gene, which they named the lov-1 gene. Note they used the acronym "lov" to stand for "location of vulva," but it does interfere with the worm's love life so it could be called the love gene! It turns out that the lov-1 gene encodes for a ciliary neural protein.

Well, that was all very interesting to worm biologists. But then things got really fascinating for human physiologists and kidney researchers. After the lov-1 gene was sequenced, its structure was fed into computerized gene database search engines and, bingo, it was found to be a very close match to the pkd-1 gene, whose mutations account for about 80% of cases of ADPKD. It turns out that ADPKD is due to a mutation in a gene that directs the synthesis of a protein found in the cell membrane, which is a critical component of the primary cilia.

The primary cilia are organelles extending from the surface of the tubule cells into the urinary lumen. We now understand that ADPKD and a number of other hereditary kidney diseases are all due to defective cilial proteins. These disorders are now called the "ciliopathies." Although we have known about the primary cilia since the late 1800s, they were considered vestigial organelles and pretty much ignored until recent years. Now we understand they have very important chemo-, mechano-, and thermosensation functions. Defects in a variety of cilial proteins cause severe cystic kidney diseases.

So we need to thank the scientists studying the sex habits of a lowly but elegant worm, C. elegans, for opening up an enormously exciting and new area of study of human disease and physiology. Basic scientific research often leads us down roads we never knew existed.

(1.) Lipton J. Mating worms and the cystic kidney: Caenorhabditis elegans as a model for renal disease. Pediatr Nephrol 2005;20(11):1531-1536.

(2.) Barr MM, Sternberg PW. A polycystic kidney-disease gene homologue required for male mating behaviour in C. elegans. Nature 1999;401(6751):386-389.

(3.) Bae YK, Barr MM. Sensory roles of neuronal cilia: cilia development, morphogenesis, and function in C. elegans. Front Biosci 2008;13:5959-5974.

(4.) Muller RU, Zank S, Fabretti F, Benzing T. Caenorhabditis elegans, a model organism for kidney research: from cilia to mechanosensation and longevity. Curr Opin NephrolHypertens 2011;20(4):400-408.

Mariana Yager, MD, and Michael Emmett, MD

From the Division of Nephrology, Department of Internal Medicine, Baylor University Medical Center at Dallas.

Corresponding author: Michael Emmett, MD, Chairman, Department of Internal Medicine, Baylor University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, TX 75246 (e-mail:
COPYRIGHT 2012 The Baylor University Medical Center
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2012 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Yager, Mariana; Emmett, Michael
Publication:Baylor University Medical Center Proceedings
Article Type:Editorial
Geographic Code:1USA
Date:Oct 1, 2012
Previous Article:Carcinoma of the breast in men.
Next Article:Facts and ideas from anywhere.

Terms of use | Copyright © 2018 Farlex, Inc. | Feedback | For webmasters