Comparisons between human and chimpanzee genomes indicate that a gene that may function as a wild-type or normal gene in one primate may function as a disease-causing gene in another [The Chimpanzee Sequencing and Analysis Consortium (2005). Nature 437:69–87]. For instance, the PPARG locus (regulator of adipocyte differentiation) is a wild-type allele in chimps but is clearly associated with Type 2 diabetes in humans. What factors might cause this apparent contradiction? Would you consider such apparent contradictions to be rare or common? What impact might such findings have on the use of comparative genomics to identify and design therapies for disease-causing genes in humans?

Key Concepts

Genetic Variation

Genetic variation refers to the differences in DNA sequences among individuals within a species or between species. These variations can lead to different phenotypes, including susceptibility to diseases. In the context of the question, the PPARG locus illustrates how a gene can have different effects in humans and chimpanzees due to variations in their genomes, highlighting the complexity of gene function across species.

Gene-Environment Interaction

Gene-environment interaction describes how environmental factors can influence the expression of genes and, consequently, the phenotypic outcome. This concept is crucial for understanding why a gene like PPARG may be benign in one species but pathogenic in another, as differences in lifestyle, diet, and other environmental factors can modulate gene function and disease risk.

Comparative Genomics

Comparative genomics is the field of study that compares the genomic features of different organisms to understand evolutionary relationships and functional biology. This approach can reveal insights into disease mechanisms by identifying conserved and divergent genes across species. However, the findings, such as the contrasting roles of the PPARG locus, underscore the need for caution when extrapolating results from one species to another in therapeutic contexts.