Comparative genomics

Abstract

Comparative genomics harnesses the power of sequence comparisons within and between species to deduce not only evolutionary history but also insights into the function, if any, of particular DNA sequences. Changes in DNA and protein sequences are subject to three evolutionary processes: drift, which allows some neutral changes to accumulate, negative selection, which removes deleterious changes, or positive selection, which acts on adaptive changes to increase their frequency in a population. Quantitative data from comparative genomics can be used to infer the type of evolutionary force that likely has been operating on a particular sequence, thereby predicting whether it is functional. These predictions are good but imperfect; their primary role is to provide useful hypotheses for further experimental tests of function. Rates of evolutionary change vary both between functional categories of sequences and regionally within genomes. Even within a functional category (e.g. protein or gene regulatory region) the rates vary. A more complete understanding of variation in the patterns and rates of evolution should improve the predictive accuracy of comparative genom-ics. Proteins that show signatures of adaptive evolution tend to fall into the major functional categories of reproduction, chemosensation, immune response and xenobi-otic metabolism. DNA sequences that appear to be under the strongest evolutionary constraint are not fully understood, although many of them are active as transcriptional enhancers. Human sequences that regulate gene expression tend to be conserved among placental mammals, but the phylogenetic depth of conservation of individual regulatory regions ranges from primate-specific to pan-vertebrate.