Hypothesis: genes which function in a stochastic lineage commitment process are subject to monoallelic expression

The collection of genes which are now Known to be monoallelically expressed in mammals is a diverse set. In the case of the genes which encode transdu cing receptors, such as immunoglobulins or odoront receptors, monoallelic e xpression ensures that cell activity is related to encountering a unique li gand. However, some monoallelically expressed genes do not encode receptors , and in these cases the physiological purpose of monoallelic expression, i s uncertain. Even more puzzling are the cases of imprinted genes, where onl y the maternal or only the paternal allele is expressed. In this article we consider the hypothesis that some of these cases of monoallelic expression reflect the unusual instances in development in which lineage commitment r esults from a selective rather than an instructive mechanism. These mechani sms are distinguished by their reliance on either external signals (instruc tive) or internal, cell autonomous events (selective) to cause the changes in gene expression which correspond to lineage commitment. While the instru ctive mechanism predicts that lineage commitment genes will be expressed or silenced biallelically, the selective mechanism predicts that commitment g enes will be subject to monoallelic expression. Specifically, for the cases in which lineage commitment results from activating gene expression, the s elective mechanism predicts that commitment genes will be monoallelically e xpressed following commitment, such as observed recently for some cytokine and transcription factor genes. For the Gases in which extinction of gene e xpression causes commitment, the selective mechanism predicts that the comm itment genes will be monoallelically expressed prior to commitment, as for X-linked and imprinted genes.