Tracking Down a Cheating Gene
Some genes will play dirty to gain a selective advantage
This article originally appeared in the March-April 2000 issue of American Scientist.
In 1956, Yuichiro Hiraizumi, a graduate student in the laboratory of James F. Crow at the University of Wisconsin, made a remarkable discovery that contradicted a basic tenet of genetics—the principle that each chromosome of a pair has an equal chance of being passed on to the next generation. Hiraizumi was carrying out genetic studies of natural populations of the fruit fly Drosophila melanogaster, with the nominal goal of investigating genes affecting viability.
In these experiments, Hiraizumi crossed white-eyed females with red-eyed males. The females were from an inbred laboratory strain, and both members of the relevant chromosome pair carried certain mutations that produced the white eye color. The members of the corresponding chromosome pair in the males were dissimilar. One chromosome was from the laboratory strain carrying the mutations for white eyes. The other chromosome of the pair was from wild-caught flies and carried the genes for normal red eye color. These eye-color genes merely served as convenient genetic markers enabling Hiraizumi to trace the transmission of each of the two chromosomes from the males to the next generation.
According to the principles of inheritance, roughly half of the offspring from these matings should have been red-eyed, and the other half white-eyed. That's not what happened. Quite unexpectedly, a few of the mating pairs produced only red-eyed offspring. These crosses flagrantly violated genetic law: The chromosome carrying the red-eye genes (the one derived from nature) was transmitted preferentially to the offspring, whereas the other member of the chromosome pair, the one carrying the white-eye mutations, seemed not to be transmitted at all.
The name Segregation Distorter (SD) was given to chromosomes that display this unusual pattern of transmission, and geneticists now know that roughly 3 to 5 percent of nearly every natural population of Drosophila melanogaster harbors SD chromosomes.
But the very notion that such transmission distortions can take place is disturbing to anyone who considers questions of evolution and natural selection. In theory, evolution by natural selection is a rigorous process that favors the retention of genes that enhance the ability of organisms to survive and reproduce. Chromosomes and the genes they carry are supposed to be meted out equally into eggs and sperm through the specialized cell divisions called meiosis. Proper meiosis ensures competing genes equal representation in the gametes and thus guarantees that each gene is exposed equally to the forces of selection.
A particular gene that figured out a way to beat the system by ending up in the vast majority of functional gametes would have an enormous but unfair advantage over competing genes. Such cheating genes would tend to increase in a population even if they conferred no selective advantage—or, indeed, were harmful to the organisms in which they were present. In principle, a situation like this could lead to the extinction of a population.
The potent impact such genes could have on natural populations was first pointed out in 1957 in a theoretical paper by Laurence M. Sandler and Edward Novitski of Oak Ridge National Laboratory. They coined the phrase "meiotic drive" to refer to any alteration of meiosis that resulted in excess transmission of one genetic variant over its alternative. The definition has now been expanded to include any alteration in meiosis or the subsequent production of gametes that results in preferential transmission of a particular genetic variant.
Examples of meiotic drive have now been discovered in a wide variety of organisms, including fungi, higher plants, insects and mammals. The mechanisms by which these various meiotic-drive systems operate remain almost a complete mystery. However, members of my laboratory have recently made substantial progress in unraveling one of them—the SD system—the very one discovered by Hiraizumi more than 40 years ago.