ANOTHER direct challenge has been posed to one of the cornerstones of biology, Mendel鈥檚 laws of inheritance.
Mendel鈥檚 laws underlie almost all of genetics. They state, for example, that it is the combination of dominant and recessive genes inherited from the parents that dictates an offspring鈥檚 characteristics.
In the main, this is true, but examples of inherited traits are being discovered that deviate from this rule. These 鈥渆pigenetic鈥� effects are caused not by genes themselves, but by inherited factors that affect gene expression in later generations. The latest such effect, described by a team led by Minoo Rassoulzadegan at Sophia Antipolis University in Nice, France, shows that RNA, as well as DNA, can carry information from one generation to another 鈥� a clear violation of the cherished notion of Mendelian inheritance.
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鈥淩NA as well as DNA can carry information from one generation to another 鈥� a violation of Mendelian rules鈥�
Rassoulzadegan鈥檚 team investigated mice that carry different versions of a gene known as Kit. Mice that carry two normal copies of the gene have brown tails. Mice bred in the laboratory to carry one normal copy of the Kit gene, and a copy of a different version called Kittm1Alf, grow tails with white spots. It was when the team bred these two types of mice together that things became really interesting.
The Kittm1Alf copy of the gene is dominant, so mice that inherited one normal Kit gene and one Kittm1Alf gene had spotted tails, as expected. But, unexpectedly, mice that inherited two normal copies of the gene also sported spotted tails. Some form of epigenetic effect must be operating.
When the team examined sperm from males carrying one normal and one variant copy of the Kit gene, they were surprised to find that it contained RNA, as well as the DNA of the genes. And it is this RNA, the team proposes, that is responsible for the epigenetic effect. The researchers injected this RNA into fertilised eggs of normal mice, which do not carry the Kittm1Alf gene, and found that the treated eggs developed into mouse pups with spotted tails (Nature, vol 441, p 469).
鈥淥ur results reveal an unexpected mode of epigenetic inheritance by the zygotic transfer of RNA molecules,鈥� says Rassoulzadegan, though how the RNA does this is not known. It could, for example, work by interfering with the way a gene is expressed, a known effect of some RNAs that is called RNA interference (see below). In any case, Rassoulzadegan speculates that the phenomenon is not unique to the Kit gene.
鈥淭hese phenomena, which a geneticist notices as oddities of genetic crosses, are likely to be just a tip of the iceberg. They point to a much larger role of epigenetics in cellular differentiation and development,鈥� says Amar Klar, of the Gene Regulation and Chromosome Biology lab at the National Cancer Institute, Frederick, Maryland.
