Cancer Genetics

A Robertsonian translocation suppresses a somatic recombination pathway to loss of heterozygosity. Haigis, K. M. & Dove, W. F. Nature Genet. 25 November 2002 (10.1038/ng1055)

The C57BL/6 ApcMin/+ mouse, which carries a germline mutation in the tumour-suppressor gene Apc (adenomatous polyposis coli), is a model for the colon tumorigenesis initiated by loss of human APC. The authors have shown that loss of heterozygosity of mouse Apc occurs principally by somatic recombination between homologous copies of the gene — a process that is suppressed by a (7; 18) Robertsonian translocation. General genomic instability might therefore not be required generally for tumour progression.

Mouse Models

IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Holzenberger, M. et al. Nature 4 December 2002 (10.1038/nature01298)

Mutant studies in several invertebrate species have found that members of the insulin or insulin-like signalling pathways are involved in regulating lifespan. The authors have confirmed this hypothesis in mammals by inactivating the Igf1r (insulin growth factor 1 receptor) gene in mouse. Animals that are heterozygous for an Igf1r knockout mutation live, on average, 26% longer than wild type, but are otherwise normal.

Comparative Genomics

Whole-genome analysis of photosynthetic prokaryotes. Raymond, J. et al. Science 298, 1616–1620 (2002)

Photosynthesis is one of the biological processes that have had the greatest impact on life on earth, but its origin is unclear. The authors carried out a whole-genome comparison of representatives from each of the five photosynthetic groups of bacteria and have found that many orthologues, including photosynthesis-specific genes, have undergone substantial lateral gene transfer. The fact that different genes have had very different evolutionary histories explains the inconsistent phylogenies that have been built using more limited gene sets.

Evolution

Dobzhansky–Muller incompatibilities in protein evolution. Kondrashov, A. S. et al. Proc. Natl Acad. Sci. USA 99, 14878–14883 (2002)

By analysing the fitness landscape of 32 proteins, the authors find that ∼10% of human pathogenic missense mutations are residues that occur naturally in the non-human orthologues. This observation suggests that the proteins in non-human species frequently (and rapidly) accumulate mutations that compensate for the otherwise deleterious variant. The authors' study further shows that these compensatory mutations usually fall in the same protein.