Chaperonomics, a new tool to study ageing and associated diseases

Abstract

The participation of molecular chaperones in the process of senescence and in the mechanisms of age-related diseases is currently under investigation in many laboratories. However, accurate, complete information about the number and diversity of chaperone genes in any given genome is scarce. Consequently, the results of efforts aimed at elucidating the role of chaperones in ageing and disease are often confusing and contradictory. To remedy this situation, we have developed chaperonomics, including means to identify and characterize chaperone genes and their families applicable to humans and model organisms. The problem is difficult because in eukaryotic organisms chaperones have evolved into complex multi-gene families. For instance, the occurrence of multiple paralogs in a single genome makes it difficult to interpret results if consideration is not given to the fact that similar but distinct chaperone genes can be differentially expressed in separate cellular compartments, tissues, and developmental stages. The availability of complete genome sequences allows implementation of chaperonomics with the purpose of understanding the composition of chaperone families in all cell compartments, their evolutionary and functional relations and, ultimately, their role in pathogenesis. Here, we present a series of concatenated, complementary procedures for identifying, characterizing, and classifying chaperone genes in genomes and for elucidating evolutionary relations and structural features useful in predicting functional properties. We illustrate the procedures with applications to the complex family of hsp70 genes and show that the kind of data obtained can provide a solid basis for future research.