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BIOLOGISTS firmly believe that parentscannot transmit to their children thetraits they acquire during their lifetimes.Though a language can be learnt andpassed on to the younger generation,when it comes to heritable traits, theDarwinian theory of evolution remainsthe cornerstone of existing knowledgeof evolution of life. So, if muscles aredeveloped by exercise, that does notimply that the progeny is likely to growup to be more muscular than other children. A recent paper by IrmgardRoemer and her team from Berlin andCambridge raises the startling possibility that certain acquired traits mayindeed be inherited (Current Biology, Vol 7, No 4).
The starting point of Roemer's studywas the observation that in two strainsof laboratory mice (named B and D forshort), certain nuclear transplantationexperiments between the strains werecausing alterations in patterns of geneexpression. Three factors play a role inthis. First, the genome of the developingembryo, which is surrounded by aninternal environment, the cytoplasm,derived from its mother. Second, thegenetic material derived from the mother via the nucleus of the egg. Andfinally,an equal complement of genetic material coming from the nucleus of thefather's sperm.
When specimens from either of thestrains B and D are bred within thestrain, the resulting embryo can bedenoted by the symbols BBB or DDD, inaccordance with the three factors ofmaternal cytoplasmic environment,maternal genes, and paternal genes. Ahybrid formed by mating a B motherwith a D father would be BBD, while onederived from a D mother and B fatherwould be DDB, as two of the three influencing factors come from the mother.In all these cases, as also in other conventional crosses between a hybrid andeither parental type, the pattern of proteins synthesised by the embryo is whatone might term normal.
In striking contrast, two proteins arestrongly repressed in both BDB and DBDhybrids. These are artificially generatedembryos and can never occur in nature.For example, BDB implies that a D-typefemale nucleus is surrounded, not by itsown cytoplasm as is normally the case,but by B-type cytoplasm. In order togenerate such a 'nucleocytoplasmic,hybrid, the nucleus from a D egg has tobe removed and transplanted into a Begg, after the removal of its own nucleus.Curiously, the two proteins withdepressed levels of expression in BDBand DBD hybrids have interrelated functions. One belongs to the class of majorurinary proteins (mup) and the other isan olfactory marker protein (Omp). ompis expressed in the mucosal layer in thenose and transported to the olfactorybulb at the front of the brain. There, incombination with molecules such asmup, it is involved in 'presenting'pheromones, or sexual attractants, tothe brain.
What this goes to show is that earlyenvironmental influences - in this casethe environment provided by the cytoplasm of the egg - can have long-lasting implications on gene expression.Also, given the nature of the affectedproteins, the effect appears to extend toadult behaviour (though this has not been tested).
What was more important was thatthe altered patterns of gene expressionfound in nucleocytoplasmic (NC)hybrids continued into the next generation. This was true even when an NChybrid male was crossed with a B or D-type female. The significance of this liesin that the cytoplasm of the newly fertilised embryo, which contains somegenetic information within structurescalled mitochondria, is derived almostentirely from the mother. However, theonly genes that an Nc hybrid male canpass on are those that are contained inits nucleus. Therefore if an Nc hybridmale can transmit changed patterns ofgene expression, it signifies that a characteristic acquired early in life was successfully passed down in a hereditary fashion.
The researchers have suggested anexplanation that accords with modernDarwinian theory. It was observed thatin all cases in which an animal showed areduction in the level of expression ofthe mup protein, there was a concomitant change in the mup gene: it had anincreased number of methyl groupsattached to the DNA.
Studies of many systems over anumber of years have shown that, firstly, methylation Of DNA can affect thelevel of expression of the protein encoded in that molecule. Secondly, the levelof methylation, which can be influencedby external cues, can also persist overgenerations. In other words, a changedpattern of gene expression can occur,not only because of a mutational changein the conventional sense, but becauseof a reversible chemical modification(in this case, methylation) of the DNA.And if the modification does not revertin the immediately succeeding generation, the change can persist. Indeed, 'there is an example in which methylation increases stepwise from one gener,ation to the next, and leads to a steadygenerational increase in the severity ofthe effects it causes.
The results indicate that theenvironment within which early embryonic development takes place couldhave long-term, transgenerationaleffects. This should make scientistswary of assuming that in vivo fertilisation or embryo cloning will haveno long-term effects. The findingssupport the belief that even seeminglymundane causes have the potential toharm future generations.