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Our genes are changing!
Although we hear about genes we have in common with chimps, birds or other living creatures, these comparisons can be confusing. The percentage of shared genes usually refers only to those that encode instructions for making proteins — overlooking all the regulatory genes that make up a large part of our genome. "Humans and fish, for instance, share about 70% of their protein-coding genes, but only about 0.5% of an important class of regulatory genes — ones that give rise to so-called long non-coding RNAs, or lncRNAs," according to Dr. Igor Ulitsky of the Biological Regulation Department at the Weizmann Institute of Science.
LncRNAs (pronounced link-RNAs) until recently received much less attention than protein-coding genes, but are increasingly of interest to science. Not only are there as many as 20,000 lncRNA genes in the human genome — about the same number as protein-coding RNAs — but lncRNAs are being revealed to be master switches in a wide variety of biological processes. They turn genes on and off, affect other regulatory genes, control cell fate during fetal development, as well as in cell division and at the death of adult organisms. They may hold the key to explaining — or even treating — a variety of diseases.
To make sense of lncRNAs, scientists are trying to understand how they appeared in the genome and if they can be grouped by activity. In a recent study published in the journal Genome Biology, Ulitsky and his team managed to identify a class of mammalian lncRNAs that had evolved from more ancient genes through adoption of new functions.
"Just as bricks from a ruined monument can help build a new house, so genes that went out of use can find new roles in the cell in the course of evolution."
Starting with the assumption evolution is an economical process, researchers believe if a gene loses its function, it is likely to be "recycled" for different purposes in the cell. On that premise, Ulitsky's team developed a series of algorithms enabling them to find "recycled" genes in the mammalian genome. First, they distinguished nearly 1,000 genes that code proteins in chickens, fish, lizards and other non-mammalian vertebrates. But not in humans, dogs, sheep and other mammals. The scientists hypothesized that at least some of these genes, after losing their protein-coding function, started manufacturing lncRNAs in mammals.
By comparing "gene neighborhoods" in the vicinity of lncRNAs and newer genes which had stopped coding for proteins, researchers found that about 60 lncRNA genes in mammals — or 2% to 3% of lncRNAs shared by humans and other mammalian species — appear to be derived from ancestral genes. Their genetic sequence in some cases is similar to that of ancient genes, but has lost the protein-coding ability.
"It is hard to know what caused these genes to lose their protein-coding potential more than 200 million years ago, when mammals evolved from their vertebrate ancestors. But the fact that these genes have been conserved in the genome for so long suggests that they play important roles in the cell."
Identifying such "fossils" of protein-coding genes in the mammalian genome will facilitate further study of human lncRNAs and may ultimately help scientists understand what happens when their function is disrupted. For example, lncRNAs help create different types of neurons in the fetal brain; their failure to properly determine the fate of these neurons may contribute to epilepsy. Because lncRNAs are involved in controlling cell division, their malfunction may be implicated in cancer. Finally, manipulating lncRNAs may make it possible to treat certain genetic disorders.
Ulitsky goes on to explain one particular lncRNA that supports the theory: "In recent years, lncRNAs were found to be important for the activation or repression of genes relevant to a variety of disorders. It may one day be possible to treat these disorders by targeting the lncRNAs so as to reprogram entire gene regulatory networks. For example, in a study in mice, researchers at the Baylor College of Medicine in Houston, Texas, had averted progression of Angelman syndrome, caused by mutations on chromosome 15, by silencing a particular lncRNA — to unleash expression of a gene that it represses."
• ETH-JH cascade in adult males regulates short-term courtship memory retention
• JH is required for retention of memory from pheromone-independent experiences
• The action of JH on memory has an early-adult-specific critical period
• JH targets DA neurons to regulate male courtship memory
Formation and expression of memories are critical for context-dependent decision making. In Drosophila, a courting male rejected by a mated female subsequently courts less avidly when paired with a virgin female, a behavioral modification attributed to “courtship memory.” Here we show the critical role of hormonal state for maintenance of courtship memory. Ecdysis-triggering hormone (ETH) is essential for courtship memory through regulation of juvenile hormone (JH) levels in adult males. Reduction of JH levels via silencing of ETH signaling genes impairs short-term courtship memory, a phenotype rescuable by the JH analog methoprene. JH-deficit-induced memory impairment involves rapid decay rather than failure of memory acquisition. A critical period governs memory performance during the first 3 days of adulthood. Using sex-peptide-expressing “pseudo-mated” trainers, we find that robust courtship memory elicited in the absence of aversive chemical mating cues also is dependent on ETH-JH signaling. Finally, we find that JH acts through dopaminergic neurons and conclude that an ETH-JH-dopamine signaling cascade is required during a critical period for promotion of social-context-dependent memory.
All authors: Sang Soo Lee, Yike Ding, Natalie Karapetians, Crisalejandra Rivera-Perez5, Fernando Gabriel Noriega, Michael E. Adams6,'Correspondence information about the author Michael E. Adams
Keywords: ecdysis triggering hormone, juvenile hormone, dopamine, courtship conditioning, learning
Dr. Igor Ulitsky's research is supported by the Abramson Family Center for Young Scientists; Rising Tide; and Mr. and Mrs. Gary Leff. Dr. Ulitsky is the incumbent of the Sygnet Career Development Chair for Bioinformatics.
The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.
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Unraveling the chromosome reveals that DNA must be wound extremely tight around histones
in order to fit its 2 meters of chromosomes within the cell nucleus.
Image Credit: US National Library of Medicine