Genome projects arescientific endeavours that ultimately aim to determine the completegenome sequence of anorganism (be it ananimal, aplant, afungus, abacterium, anarchaean, aprotist or avirus) and to annotate protein-codinggenes and other important genome-encoded features.[1] The genome sequence of an organism includes the collectiveDNA sequences of eachchromosome in the organism. For abacterium containing a single chromosome, a genome project will aim to map the sequence of that chromosome. For the human species, whose genome includes 22 pairs ofautosomes and 2 sex chromosomes, a complete genome sequence will involve 46 separate chromosome sequences.
TheHuman Genome Project is a well known example of a genome project.[2]
Genome assembly refers to the process of taking a large number of shortDNA sequences and reassembling them to create a representation of the originalchromosomes from which the DNA originated. In ashotgun sequencing project, all the DNA from a source (usually a singleorganism, anything from abacterium to amammal) is first fractured into millions of small pieces. These pieces are then "read" by automated sequencing machines. A genome assemblyalgorithm works by taking all the pieces and aligning them to one another, and detecting all places where two of the short sequences, orreads, overlap. These overlapping reads can be merged, and the process continues.
Genome assembly is a very difficultcomputational problem, made more difficult because many genomes contain large numbers of identical sequences, known asrepeats. These repeats can be thousands of nucleotides long, and occur different locations, especially in the large genomes ofplants andanimals.
The resulting (draft) genome sequence is produced by combining the information sequencedcontigs and then employing linking information to create scaffolds. Scaffolds are positioned along thephysical map of the chromosomes creating a "golden path".
Originally, most large-scale DNA sequencing centers developed their own software for assembling the sequences that they produced. However, this has changed as the software has grown more complex and as the number of sequencing centers has increased. An example of suchassemblerShort Oligonucleotide Analysis Package developed byBGI for de novo assembly of human-sized genomes, alignment,SNP detection, resequencing, indel finding, and structural variation analysis.[3][4][5]
Since the 1980s,molecular biology andbioinformatics have created the need forDNA annotation. DNA annotation or genome annotation is the process of identifying attaching biological information tosequences, and particularly in identifying the locations of genes and determining what those genes do.
Whensequencing a genome, there are usually regions that are difficult to sequence (often regions with highlyrepetitive DNA). Thus, 'completed' genome sequences are rarely ever complete, and terms such as 'working draft' or 'essentially complete' have been used to more accurately describe the status of such genome projects. Even when everybase pair of a genome sequence has been determined, there are still likely to be errors present because DNA sequencing is not a completely accurate process. It could also be argued that a complete genome project should include the sequences ofmitochondria and (for plants)chloroplasts as theseorganelles have their own genomes.
It is often reported that the goal of sequencing a genome is to obtain information about the complete set ofgenes in that particular genome sequence. The proportion of a genome that encodes for genes may be very small (particularly ineukaryotes such as humans, wherecoding DNA may only account for a few percent of the entire sequence). However, it is not always possible (or desirable) to only sequence thecoding regions separately. Also, as scientists understand more about the role of thisnoncoding DNA (often referred to asjunk DNA), it will become more important to have a complete genome sequence as a background to understanding the genetics and biology of any given organism.
In many ways genome projects do not confine themselves to only determining a DNA sequence of an organism. Such projects may also includegene prediction to find out where the genes are in a genome, and what those genes do. There may also be related projects to sequenceESTs ormRNAs to help find out where the genes actually are.
Historically, when sequencing eukaryotic genomes (such as the wormCaenorhabditis elegans) it was common to firstmap the genome to provide a series of landmarks across the genome. Rather than sequence a chromosome in one go, it would be sequenced piece by piece (with the prior knowledge of approximately where that piece is located on the larger chromosome). Changes in technology and in particular improvements to the processing power of computers, means that genomes can now be 'shotgun sequenced' in one go (there are caveats to this approach though when compared to the traditional approach).
Improvements inDNA sequencing technology have meant that the cost of sequencing a new genome sequence has steadily fallen (in terms of cost perbase pair) and newer technology has also meant that genomes can be sequenced far more quickly.
When research agencies decide what new genomes to sequence, the emphasis has been on species which are either high importance asmodel organism or have a relevance to human health (e.g. pathogenicbacteria orvectors of disease such asmosquitos) or species which have commercial importance (e.g. livestock and crop plants). Secondary emphasis is placed on species whose genomes will help answer important questions inmolecular evolution (e.g. thecommon chimpanzee).
In the future, it is likely that it will become even cheaper and quicker to sequence a genome. This will allow for complete genome sequences to be determined from many different individuals of the same species. For humans, this will allow us to better understand aspects ofhuman genetic diversity.
Many organisms have genome projects that have either been completed or will be completed shortly, including:
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