A controversial report announced today by the 10 person Commons Select Committee on Science and Technology , though endorsed by only 5 of them, recommends amongst other things the relaxation of constraints on human embryo sex selection during the practice of in vitro fertilisation-assisted conception. It further proposes the relaxation of controls on embryo selection on the basis of other gene-based tests ( PGD, pre-implantation genetic diagnosis) as well as recommending the dissolution of the current regulatory body the Human embryology and fertilisation commission (HFEA). Ironically, a general media hubbub articulated by the usual hot-headed advocacy groups and typified by claims that the report represents a rank piece of gradualism which puts us on the hubristic slippery slope to designer babies and a morally shaky new world , has threatened to overwhelm a piece of really exciting genetic news which could itself put a significant question mark against the post-Mendelian doctrines about DNA and inheritance on which PGD is based.
A group of plant geneticists led by Bob Pruitt at Purdue University report in the journal Nature today (Lolle et al Nature 434, 505-509, 24 th March 2005), their studies of a high frequency reversion of a phenotype in Arabidopsis (Thale cress) called Hothead, a phenotype which is manifest as a fusion of normally distinct organs. Phenotypic reversion comes about via the replacement in progeny (10%) of a mutant (hth) allele at the hothead locus by a wild type allele (HTH). However, the parental lines do not contain the HTH allele though grand parental lines do .
The authors dare to suggest that this represents a serious violation of Mendelian inheritance , and by careful experiment demonstrate that this is in fact the case.
Examples of non-Mendelian behaviour are not unknown but are generally represented by rare events which can be explained by reversible DNA sequence rearrangements or by some form of recombination between remote but related loci. Lolle et al rule out this possibility as an explanation for the restoration of the original allele at the hothead locus by demonstrating that non of the hothead-related loci in the Arabidopsis genome contain DNA sequence which could have provided a corresponding template for correction.
They are forced to conclude that the restorative template resides elsewhere than in the DNA component of the genome and postulate instead a cache of ancestral RNA. The nature of this cache is unknown but could exist within the ubiquitous population of small RNAs involved in gene regulation and chromatin modification.
Lolle et al go on to demonstrate that restoration of grand parental alleles is not unique to the hothead locus but occurs, though less frequently, at other loci. The phenomenon, they suggest may provide a means of testing new mutations in the homozygous condition without losing the option of reverting to the original via a conserved non-DNA template.
We are left wondering how widespread the phenomenon is, as well as pondering what its implications might be for predicting genetic outcomes from DNA data alone. Might it only exist in plants where there is an alteration of generations (successive vegetative - sporophytic and reproductive- gametophytic developmental stages). Or might it have significance equally to animals where the vegetative and reproductive lineages have separate but parallel trajectories. Either way, this new hint that other things than chromosomal DNA might participate in genetic continuity should reactivate our scepticism about being able to design anything as complex as a baby.