Mother's Little Favorite Scientific American Jul 92
A spiteful gene ensures, "Like mother, like child"
In the words of one hymm to motherhood, "M is for the many things she gave me." If Mom is Tribolium castaneum the flour beetle, one of her gifts had better be a gene called Medea. As three Kansas entomologists have learned, if a female beetle carries Medea, any of her offspring that lack the gene will die in the cradle. Its discoverers puckishly declare that Medea is an acronym for "maternal effect dominant embryonic arrest," but don't be fooled: their real inspiration was Medea of Greek mythology, who killed her children in a jealous rage. Medea seems to represent the first member of a previously unnoticed class of so-called selfish genes. Such genes may play an important part in evolution and the origin of new species. Selfish genes are parasitic sequences of DNA that increase their own frequency in a population, usually to the detriment of the organisms that carry them. Although most genes can prosper orily by contributing to the well-being of their bearers, "there are certain times in the life cycle of an organism when genetic elements can potentially cheat and gain a transmission advantage," explains Jack H. Werren, who studies selfish genes at the University of Rochester. Some genes cheat by inserting extra copies of themselves into cells; some cripple or obliterate their genetic counterparts on other chromosomes. A few can even change the sex of their host so that it produces only eggs or sperm favorable to the gene's distribution. Virtually all species, including humans, harbor at least some selfish genes. "It's a jungle in there," Werren quips. Medea is remarkable because it is the first maternally inheriteded selfish gene that acts on embryos rather than ova or sperm. Richard W. Beeman of the Agricultural Research Service in Manhattan, Kan., and Ws colleagues Kenlee S. Friesen and Rob E. Denell of Kansas State University became aware of Medea while testing whether flour beetles from different parts of the world had any problems breeding with one another. When they tried to cross beetles from a rice warehouse in Singapore with ones from a farm in Georgia, they noticed that some of the hybrid combinations had consistently small broods: many of the resulting larvae died before or during hatching. rther experiments, which Beeman, Friesen and Denell described in Science in April, convinced them that the deaths could be attributed to the activity of a selfish maternal gene killing noncarriers in the next generation. The lethality is linked strictly to the maternal line, Beeman observes. "If the father carries it and the mother doesn't, everything is normal," he says. "You wouldn't know the gene was there." Destroying offspring may seem counterproductive from the standpoint of the beetles, but it suits the gene's purpose by eliminating the competition-in this case, individuals that cannot transmit it further. When Medea is carried by a female, the gene raises its frequency in the next generation by eliminating larvae that lack it. Males carrying Medea can meanwhile mate indiscriminately and infect other pedigrees Mth the gene. As Medea spreads, many larvae die, but the gene can eventually overtake an entire population. "Once it becomes fixed in a population, it becomes invisible, which may be why no one discovered it before," Beeman says. No one yet knows how Medea exerts its murderous influence. one possibility is that the gene has two products, one a poison, the other its antidote. If the poison persists in the mother's eggs, Medea-free offspring developing from those eggs might die because they are unable to counteract it. (Some selfish genetic elements in primitive bacteria are known to operate in a similar manner.) Beeman believes that if the Medea gene can be specifically located and cloned, its killing mechanism may eventually become clear. The existence of Medea invites speculation about the possible role of selfish genes in evolution. New species can arise when reproductive barriers, such as distance or mutations, spht up populations. If factors resembling Medea appear commonly in nature, they could contribute to that isolation by making it difficult for strangers to join a protected population. Both Beeman and Werren caution, however, that the actual isolating effects of Medea and other selfish genes remain to be demonstrated. There is reason to suspect that Medea-like selfish genes could be widespread among animals and plants. Once they knew what to look for, Beeman and his colleagues quickly found factors resembling Medea in other populations of flour beetle and in a completely different beetle species. Crossbreeding experiments in other species could uncover new analogues of Medea. Notwithstanding its selfishness, Medea could sometimes tum out to be surprisingly advantageous for its hosts after aH. Werren argues that for many mammals, insects, plants and other orgarlisms, the chief competitors of any individual are actually its siblings, who share the same enviromnent and consume the same resources. By weeding out some siblings for its own purposes, Medea may indirectly enhance the fitness of its carriers-thus boosting its own success still more. As biologists continue to investigate the growing ranks of selfish genes, even more crafty proliferation strategies are likely to emerge. if someone can work out an appropriate acronym, perhaps the next selfish gene will be called Machiavelli. -John Rennie
Alu sequences may be a factor in Primate Evolution New Scientist 25 Sept 95
THE human genome is littered with "junk" DNA that everyone used to think had no real function. But now one of the most common types of genetic junk turns out to contain a working copy of a genetic switch that activates other genes. The junk sequence, known as Alu, may have played an important role in the evolution of primates, says Wanda Reynolds of the Sidney Kimmel Cancer Center in San Diego. Alu is a 283-nucleotide sequence that acts as a "jumping gene". From time to time, it inserts copies of itself randomly into the genome. Over the past 30 to 60 million years these insertions have occurred repeatedly, leaving roughly a million copies of Alu scattered through the human genome and making up almost 10 per cent of all the DNA in each cell. During this time, the sequences of the various Alus have begun to diverge, so that four distinct subfamilies of Alu can now be recognised. While studying one of these subfamilies, Reynolds noticed a short stretch of DNA only 14 bases long- that looked familiar. Elsewhere in the genome, there are nearly identical sequences that function as anchor points for proteins that bind to hormones and which therefore provide a way for hor mones to turn genes on and off. Reynold and her colleague Gordon Vansant learned that the Alu sequence also binds to a hor mone receptor-in this case, the receptor for a hormone called retinoic acid, whic activates genes at the proper times durin development (Proceedings of the National Academy of Sciences, vol 92, p 8229). Vansant and Reynolds then turned their attention to a naturally occurring Alu that sits close to the human gene for keratin, protein found in our skin, hair and nails They looked at cells in which they had re placed the keratin gene with a "marker' gene whose activity could be easily mea sured. When the researchers then delete the Alu sequence, they found that th marker gene became 35 times less active. Since submitting their paper for publica tion, they have found functional bindin sites for the retinoic acid receptor in second subfamily of Alus. This subfamil also contains sequences that bind to thyroi hormone receptors, says Reynolds, "so th story is going to get even more interesting" A few Alus have previously been sho to affect the activity of nearby genes, but the new study is the first to show how. The results also provide the first clear evidence that most Alus could have the potential to regulate human genes. Other researchers have been hunting for similar effects but without success. "I've been looking for mobile elements carrying out significant regulatory roles, and I've made little progress," says Roy Britten of the California Institute of Technology in Pasadena. Reynolds believes that most Alus have little effect on nearby genes, perhaps because they are bundled deep within folds of DNA. But she says that with a million Alus strewn randomly through the genome during the course of primate evolution, at least a few are likely to have landed where they could regulate a nearby gene. When this occurred, she suggests, the effect would be equivalent to randomly twisting a knob on an instrument panel. Usually the effect would be harmful, but once in a while it might produce an interesting and beneficial genetic novelty. "We can't prove it," she says, "but it seems that over the last 30 to 50 million years, it would provide good evolutionary fodder." Bob Holmes, Santa Cruz