Question

Process of decode the human code

Answer 1

GENOMES
The ability to undertake DNA sequencing on a large scale started a revolution in biology, as it became possible to determine the complete DNA sequence of any organism and therefore obtain a full description of genes and other important biological information stored in the genome. For the first time, it was possible to define the complete set of proteins required for a particular life form, to make full comparisons of protein sets between different species, to discover the basis of their similarities and differences and to explore the evolutionary relationship between them. For example, the 15 Mb genome sequence of baker’s yeast Saccharomyces cerevisiae, completed in 1996, contains >6000 genes(1,2). These encode all the functions required for a eukaryotic cell. The 99 Mb genome sequence of the free-living soil nematode worm Caenorhabditis elegans, completed 2 years later, contains 19 000 genes (3). This constitutes a complete gene set for a multicellular organism, encoding proteins involved in basic eukaryotic cell functions and also many others involved, for example, in development, cell–cell interactions, motility, feeding and reproduction. A recent cross comparison of the complete gene sets (4) has revealed that 23% of the proteins encoded by yeast genes have apparent homologues in the nematode worm, reflecting functions common to both organisms. A closer examination of matches between individual protein domains illustrates another level of homology, with 41% of yeast proteins matching at least one protein domain in a nematode protein and 36% being homologous to a representative mammalian protein set (4). It is evident that diversity of function has arisen in evolution as a result of existing domains being used in new combinations, as well as from the generation of entirely new proteins.
These model genome projects used a strategy by which a physical map was constructed of overlapping bacterial or yeast artificial chromosome (YAC) clones representing the entire genomic DNA of the organism (5–7). A minimum overlapping set of clones (the tile path) was then chosen for sequencing. Each clone was then subjected to complete sequencing, comprising an initial random shotgun phase followed by a phase of directed finishing, resulting in a final reference sequence with an accuracy of >99.99% (8). Completion of these model genomes thus provided many important technological and biological insights that have since been applied to the human genome.
The extraordinary progress of the Human Genome Project was made possible by the remarkable international collaboration which developed from the early 1990s. Fostered by the close co-operation of multiple national funding agencies, 20 centres in six countries have worked together (see Appendix), co-ordinating their efforts by sharing technology, resources and information which were freely available throughout the project. Sequencing in many laboratories was also co-ordinated substantially using the genome map itself. This helped to minimize unnecessary duplication and to allow both large and small partners to contribute effectively. The development of new automated sequencing technology, coupled with the adoption of streamlined approaches to generating genome sequence information on a large scale, led to a dramatic acceleration of the programme during the last 2 years, driven by a growing awareness of the enormous value of gaining a first view of the human genome. The result is the emergence of the ‘working draft’. Although incomplete, it provides extensive coverage of most of the human genes. The working draft is therefore both an advanced intermediate on the pathway to the production of the finished reference sequence and a product of immediate value in accelerating studies of individual genes, associations with disease and the study of human sequence variation. The working draft is a dynamic product, subject to continual refinement as new data are added. A brief summary of the strategy, milestones and status of the international programme is outlined below, based on current information that is publicly available..