Comparative genomics: the key to understanding the human genome project

The sequencing of the human genome is well underway. Technology has advanced, such that the total genomic sequence is possible, along with an extensive catalogue of genes via comprehensive cDNA libraries. With the recent completion of the Saccharomyces cerevisiae sequencing project and the imminent completion of that of Caenorhabditis elegans, the most frequently asked question is how much can sequence data alone tell us? The answer is that that a DNA sequence taken in isolation from a single organism reveals very little. The vast majority of DNA in most organisms is noncoding. Protein coding sequences or genes cannot function as isolated units without interaction with noncoding DNA and neighboring genes. This genomic environment is specific to each organism. In order to understand this we need to look at similar genes in different organisms, to determine how function and position has changed over the course of evolution. By understanding evolutionary processes we can gain a greater insight into what makes a gene and the wider processes of genetics and inheritance. Comparative genomics (with model organisms), once the poor relation of the human genome project, is starting to provide the key to unlock the DNA code. BioEssays 1999;21:121–130. © 1999 John Wiley & Sons, Inc.

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