An image of the 46 chromosomes, making up the diploid genome of human male. (The mitochondrial chromosome is not shown.)

In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA.^[1]

Origin of term[link]

The term was adapted in 1920 by Hans Winkler, Professor of Botany at the University of Hamburg, Germany. The Oxford English Dictionary suggests the name to be a blend of the words gene and chromosome. A few related -ome words already existed, such as biome and rhizome, forming a vocabulary into which genome fits systematically.^[2]

Overview[link]

Some organisms have multiple copies of chromosomes, diploid, triploid, tetraploid and so on. In classical genetics, in a sexually reproducing organism (typically eukarya) the gamete has half the number of chromosomes of the somatic cell and the genome is a full set of chromosomes in a gamete. In haploid organisms, including cells of bacteria, archaea, and in organelles including mitochondria and chloroplasts, or viruses, that similarly contain genes, the single or set of circular and/or linear chains of DNA (or RNA for some viruses), likewise constitute the genome. The term genome can be applied specifically to mean that stored on a complete set of nuclear DNA (i.e., the "nuclear genome") but can also be applied to that stored within organelles that contain their own DNA, as with the "mitochondrial genome" or the "chloroplast genome". Additionally, the genome can comprise nonchromosomal genetic elements such as viruses, plasmids, and transposable elements.^[3]

When people say that the genome of a sexually reproducing species has been "sequenced", typically they are referring to a determination of the sequences of one set of autosomes and one of each type of sex chromosome, which together represent both of the possible sexes. Even in species that exist in only one sex, what is described as "a genome sequence" may be a composite read from the chromosomes of various individuals. In general use, the phrase "genetic makeup" is sometimes used conversationally to mean the genome of a particular individual or organism. The study of the global properties of genomes of related organisms is usually referred to as genomics, which distinguishes it from genetics which generally studies the properties of single genes or groups of genes.

Both the number of base pairs and the number of genes vary widely from one species to another, and there is only a rough correlation between the two (an observation known as the C-value paradox). At present, the highest known number of genes is around 60,000, for the protozoan causing trichomoniasis (see List of sequenced eukaryotic genomes), almost three times as many as in the human genome.

An analogy to the human genome stored on DNA is that of instructions stored in a book:

• The book (genome) would contain 23 chapters (chromosomes);
• each chapter contains 48 to 250 million letters (A,C,G,T) without spaces;
• Hence, the book contains over 3.2 billion letters total;
• The book fits into a cell nucleus the size of a pinpoint;
• At least one copy of the book (all 23 chapters) is contained in most cells of our body. The only exception in humans is found in mature red blood cells which become enucleated during development and therefore lack a genome.

Sequencing and mapping[link]

In 1976, Walter Fiers at the University of Ghent (Belgium) was the first to establish the complete nucleotide sequence of a viral RNA-genome (bacteriophage MS2). The next year, Phage Φ-X174, with only 5386 base pairs, became the first DNA-genome project to be completed, by Fred Sanger. The first complete genome sequences for representatives from all 3 domains of life were released within a short period during the mid-1990s. The first bacterial genome to be sequenced was that of Haemophilus influenzae, completed by a team at The Institute for Genomic Research in 1995. A few months later, the first eukaryotic genome was completed, with the 16 chromosomes of budding yeast Saccharomyces cerevisiae being released as the result of a European-led effort begun in the mid-1980s. Shortly afterward, in 1996, the first genome sequence for an archaeon, Methanococcus jannaschii, was completed, again by The Institute for Genomic Research.

The development of new technologies has made it dramatically easier and cheaper to do sequencing, and the number of complete genome sequences is growing rapidly. The US National Institutes of Health maintains one of several comprehensive databases of genomic information.^[4] Among the thousands of completed genome sequencing projects include those for mouse, rice, the plant Arabidopsis thaliana, the puffer fish, and bacteria like E. coli.

New sequencing technologies have also opened up the prospect of personal genome sequencing as an important diagnostic tool. A major step toward that goal was the completion in 2007 of the full genome of James D. Watson, one of the co-discoverers of the structure of DNA.^[5]

Whereas a genome sequence lists the order of every DNA base in a genome, a genome map identifies the landmarks. A genome map is less detailed than a genome sequence and aids in navigating around the genome. The Human Genome Project was organized to map and to sequence the human genome. A fundamental step in the Human genome project was the release of a detailed genomic map by Jean Weissenbach and his team at the Genoscope in Paris.^[6][7]

Genome compositions[link]

Genome composition is used to describe the make up of contents of a haploid genome, which should include genome size, proportions of non-repetitive DNA and repetitive DNA in details. By comparing genome compositions between genomes, it helps people better understanding evolution history of genome.

When talking about genome composition, one should distinguish between prokaryotes and eukaryotes as the big differences on contents structure they have. In prokaryotes, most of the genome (85-90%) is non-repetitive DNA, which means coding DNA mainly forms it, while non-coding regions only take a small part^[8] . On the contrary, eukaryotes have the feature of exon-intron organization of protein coding genes; the variation of repetitive DNA content in eukaryotes is also extremely high. When refer to mammalians and plants, the major part of genome is composed by repetitive DNA^[9] .

Most biological entities that are more complex than a virus sometimes or always carry additional genetic material besides that which resides in their chromosomes. In some contexts, such as sequencing the genome of a pathogenic microbe, "genome" is meant to include information stored on this auxiliary material, which is carried in plasmids. In such circumstances then, "genome" describes all of the genes and information on non-coding DNA that have the potential to be present.

In eukaryotes such as plants, protozoa and animals, however, "genome" carries the typical connotation of only information on chromosomal DNA. So although these organisms contain chloroplasts and/or mitochondria that have their own DNA, the genetic information contained by DNA within these organelles is not considered part of the genome. In fact, mitochondria are sometimes said to have their own genome often referred to as the "mitochondrial genome". The DNA found within the chloroplast may be referred to as the "plastome".

Genome size[link]

Genome size is the total number of DNA base pairs in one copy of a haploid genome. The genome size is positively correlated with the morphological complexity among prokaryotes and lower eukaryotes; however, after Mollusks and all the other higher eukaryotes above, this correlation is no longer effective^{[10] [11]} . This phenomenon also indicates the mighty influence coming from repetitive DNA act on the genomes.

Since genomes are very complex, one research strategy is to reduce the number of genes in a genome to the bare minimum and still have the organism in question survive. There is experimental work being done on minimal genomes for single cell organisms as well as minimal genomes for multicellular organisms (see Developmental biology). The work is both in vivo and in silico.^[12][13]

Proportion of non-repetitive DNA[link]

The proportion of non-repetitive DNA is calculated by using length of non-repetitive DNA divide by genome size. Protein-coding genes and RNA-coding genes are generally non-repetitive DNA^[30] . Bigger genome doesn’t mean more genes, and the proportion of non-repetitive DNA decreases along with the increase of genome size in higher eukaryotes^[31] .

It had been found that the proportion of non-repetitive DNA can vary a lot between species. Some E. coli as prokaryotes only have non-repetitive DNA, lower eukaryotes such as C. elegans and fruit fly, still possess more non-repetitive DNA than repetitive DNA^[32][33] . Higher eukaryotes tend to have more repetitive DNA than non-repetitive one. In some plants and amphibians, the proportion of non-repetitive DNA is no more than 20%, becoming a minority component^[34].

Proportion of repetitive DNA[link]

The proportion of repetitive DNA is calculated by using length of repetitive DNA divide by genome size. There are two categories of repetitive DNA in genome: tandem repeats and interspersed repeats^[35] .

Tandem repeats[link]

Tandem repeats are usually caused by slippage during replication, unequal crossing-over and gene conversion^[36] , satellite DNA and microsatellites are forms of tandem repeats in the genome^[37] . Although tandem repeats count for a significant proportion in genome, the largest proportion in mammalian is the other type, interspersed repeats.

Interspersed repeats[link]

Interspersed repeats are mainly come from transposable elements (TEs), it also include some protein coding gene families and pseudogenes. Transposable elements are able to integrate into the genome at another site within the cell^{[38] [39]} . It is believed that TEs is an important driving force on genome evolution of higher eukaryotes^[40] . TEs can be classified into two categories, Class 1 (retrotransposons) and Class 2 (DNA transposons)^[41] .

Retrotransposons[link]

Retrotransposons can be transcribed into RNA, which then duplicated at another site into the genome^[42] . It can be divided into Long terminal repeats (LTRs) and Non-Long Terminal Repeats (Non-LTR)^[43] .

Long Terminal Repeats LTRs are similar to retroviruses, which both have gag and pol genes to make cDNA from RNA and proteins to insert into genome, but LTR can only act within the cell as they lack env gene in retroviruses^[44] . It had been reported that LTR consist largest fraction in most plant genome and might account for the huge variation in genome size^[45] .

Non-Long Terminal Repeats (Non-LTRs) Non-LTR can be divided into long interspersed elements (LINEs), short interspersed elements (SINEs) and Penelope-like elements. In Dictyostelium discoideum there is another DIRS-like elements belong to Non-LTRs. Non-LTR is widely spread in eukaryotic genomes^[46] .

Long interspersed elements (LINEs) are able to encode two Open Reading Frames (ORFs) to generate transcriptase and endonuclease, which are essential in retrotransposition. Human genome has around 500,000 LINEs, taking 17% of the genome^[47] .

Short interspersed elements (SINEs) are usually less than 500 base pairs and need to co-opt with the LINEs machinery to function as nonautonomous retrotransposons^[48] . Alu element is the most common SINEs found in primates, it length about 350 base pairs and take 11% of human genome, counts around 1,500,000 copies^[49] .

DNA transposons[link]

DNA transposons generally move by “cut and paste” in the genome, but duplication has also been observed. Class 2 TEs don’t use RNA as intermediate and are popular in bacteria, in metazoan it has also been found^[50] .

Genome evolution[link]

Genomes are more than the sum of an organism's genes and have traits that may be measured and studied without reference to the details of any particular genes and their products. Researchers compare traits such as chromosome number (karyotype), genome size, gene order, codon usage bias, and GC-content to determine what mechanisms could have produced the great variety of genomes that exist today (for recent overviews, see Brown 2002; Saccone and Pesole 2003; Benfey and Protopapas 2004; Gibson and Muse 2004; Reese 2004; Gregory 2005).

Duplications play a major role in shaping the genome. Duplications may range from extension of short tandem repeats, to duplication of a cluster of genes, and all the way to duplications of entire chromosomes or even entire genomes. Such duplications are probably fundamental to the creation of genetic novelty.

Horizontal gene transfer is invoked to explain how there is often extreme similarity between small portions of the genomes of two organisms that are otherwise very distantly related. Horizontal gene transfer seems to be common among many microbes. Also, eukaryotic cells seem to have experienced a transfer of some genetic material from their chloroplast and mitochondrial genomes to their nuclear chromosomes.

See also[link]

• Full genome sequencing
• Bacterial genome size

References[link]

Further reading[link]

• Benfey, P.; Protopapas, A.D. (2004). Essentials of Genomics. Prentice Hall. 
• Brown, Terence A. (2002). Genomes 2. Oxford: Bios Scientific Publishers. ISBN 978-1-85996-029-5. 
• Gibson, Greg; Muse, Spencer V. (2004). A Primer of Genome Science (Second ed.). Sunderland, Mass: Sinauer Assoc. ISBN 0-87893-234-8. 
• Gregory, T. Ryan (ed) (2005). The Evolution of the Genome. Elsevier. ISBN 0-12-301463-8. 
• Reece, Richard J. (2004). Analysis of Genes and Genomes. Chichester: John Wiley & Sons. ISBN 0-470-84379-9. 
• Saccone, Cecilia; Pesole, Graziano (2003). Handbook of Comparative Genomics. Chichester: John Wiley & Sons. ISBN 0-471-39128-X. 
• Werner, E. (2003). "In silico multicellular systems biology and minimal genomes". Drug Discov Today 8 (24): 1121–1127. DOI:10.1016/S1359-6446(03)02918-0. PMID 14678738. 

External links[link]

Wikiquote has a collection of quotations related to: Genome

• Build a DNA Molecule
• Some comparative genome sizes
• DNA Interactive: The History of DNA Science
• DNA From The Beginning
• All About The Human Genome Project — from Genome.gov
• Animal genome size database
• Plant genome size database
• GOLD:Genomes OnLine Database
• The Genome News Network
• NCBI Entrez Genome Project database
• NCBI Genome Primer
• GeneCards — an integrated database of human genes
• BBC News - Final genome 'chapter' published
• IMG (The Integrated Microbial Genomes system) — for genome analysis by the DOE-JGI
• GeKnome Technologies Next-Gen Sequencing Data Analysis — next-generation sequencing data analysis for Illumina and 454 Service from GeKnome Technologies.