Evolutionary dynamics of a virus in a vaccinated population

The progress of an epidemic in a small closed community is simulated by an agent-based model which allows vaccination and variation. The attributes of the virus are governed by two genetic loci: the P-locus, which determines growth, and the M-locus, which determines immune characteristics. Mutation at either locus modifies the attributes of the virus and leads to evolution through natural selection. For both loci the crucial variable is the potential mutation supply UPot, because evolution is likely to happen when UPot > 1. Mutation at the P-locus causes a limited increase in virulence, which may be affected by vaccine design. Mutation at the M-locus may cause a qualitative shift of dynamic regime from a simple limited epidemic to a perennial endemic disease by giving rise to escape mutants which may themselves mutate. A broad vaccine that remains efficacious despite several mutations at the M-locus prevents this shift and provides protection despite the evolution of the virus. Escape variants may nevertheless arise through recombination after coinfection, and can be suppressed by timely revaccination, using the prevalent strain to design the vaccine.

A novel ATPase on mouse chromosome 7 is a candidate gene for increased body fat

A region of mouse chromosome 7, just distal to the pink-eyed ( p) dilution locus, contains a gene or genes, which we have named p-locus-associated obesity ( plo1), affecting body fat. Mice heterozygous for the most distally extending chromosomal deletions of this region have nearly double the body fat of mice when the deletion is inherited maternally as when it is inherited paternally. We have physically mapped the 1-Mb critical region, which lies between the Gabrb3 and Ube3a/ Ipw genes, and DNA sequencing has localized a new member of the third subfamily of P-type ATPases to the minimal region specifying the trait. This gene, which we have called p-locus fat-associated ATPase ( pfatp) is differentially expressed in human and mouse tissues with predominant expression in the testis and lower levels of expression in adipose tissue and other organs. We propose this ATPase as the prime candidate for the gene at the plo1 locus modulating body fat content in the mouse. The unusual inheritance pattern of this phenotype suggests either genomic imprinting, known to occur in other local genes ( Ube3a, Ipw), or an effect of maternal haploinsufficiency during pregnancy or lactation on body fat in the progeny.

Molecular analysis of 36 mutations at the mouse pink-eyed dilution (p) locus.

Thirty-six radiation- or chemically induced homozygous-lethal mutations at the p locus in mouse chromosome 7 have been analyzed at 17 loci defined by molecular probes to determine the types of lesions, numbers of p-region markers deleted or rearranged, regions of overlap of deletion mutations, and genetic distances between loci. A linear deletion map of the [Myod1, Ldh3]-[Snrpn, Znf127] region has been constructed from the molecular analyses of the p-locus deletions. The utility of these deletions as tools for the isolation and characterization of the genes specifying the neurological, reproductive, and developmental phenotypes genetically mapped to this region will grow as more detailed molecular analyses continue.