Defining the function of a prolactin gene family member.

Abstract

Mouse molecular geneticists have been frustrated to find that knockout alleles do not always produce a phenotype. Prince and Pickett (1) The quotation above is a considerable understatement for all of those graduate students and postdoctoral researchers whose hopes for scientific glory, or at least a diploma, were resting on a phenotype resulting from the ablation of their gene of interest. The source of this consternation is functional redundancy, and paralogous gene families are at least one source of such redundancy. The perpetuation and expansion of gene family members is likely caused by a selective advantage that such paralogous genes provide a species in dealing with the myriad of environmental and physiological challenges (nutrient availability, predatory pressure, disease, genetic conflict, etc.) that are confronted by animals in the wild. Animals maintained in the relatively aseptic environment of modern housing facilities are not exposed to such challenges. Under these conditions, the absence of a gene family member may not produce an overt phenotype. A report in this issue of PNAS by Ain et al . (2) describes just such an occurrence after disruption of the gene for a prolactin (PRL) family member, PRL-like protein A (PLP-A). Despite the initial lack of a phenotype, they were able to gain some insight into the biological role of PLP-A by providing an appropriate environmental challenge. All animals possess numerous duplicated genes. In fact, the rate at which gene duplications occur is quite high and is comparable to the rate at which point mutations arise per nucleotide site (3–5). It is perhaps not surprising that gene duplication has long been suggested to provide the raw materials on which adaptive evolution can act (6). Indeed, expansion of gene families is often a species-specific phenomenon, with certain gene families restricted to closely related species …