Gene cluster

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A gene cluster is a group of two or more genes that encode for similar products, or protein, which collectively share a generalized function. Portions of the DNA sequence of each gene within a gene cluster is found to be identical; however, the resulting proteins of each gene is distinctive from the resulting protein of another gene within the cluster. Because of the homology (biology) of the DNA sequences, the presence of gene cluster suggests a close evolutionary relationship between two species. Therefore, gene clusters are used to assess the evolutionary relationship between different species. An example of a gene cluster is hemoglobin.

Creation of gene clusters[edit]

Coordinated gene expression, or co-expression as a result of codominance, is considered to be the most common mechanism driving the formation of gene clusters; however, coinheritance has also been considered as a driving force for the formation of gene clusters. [1] The typical eukaryotic gene was thought to be randomly distributed in the eukaryotic genome and independently expressed from its neighbor; however, evidence has been found that eukaryotic genes are not only regulated at the individual level by promoter (genetics) sequences and transcription factors but by their location within the genome. As a result, genes are nonrandomly distributed within genomes when two or more genes share similar expression levels.[2] These co-expressed genes tend to be found in a gene cluster in which the individual genes generally share a similar function, such as a metabolic pathway. The cluster is comprised of genes, specific to a particular metabolic pathway, spanning a large portion of the genome. [1]

Gene clusters may also be formed via gene duplication. Conserved gene clusters, such as Hox and the human β-globin gene cluster, may be formed as a result of the process of gene duplication and divergence. A gene is duplicated during cell division, so that its descendants have two end-to-end copies of the gene where it had one copy, initially coding for the same protein or otherwise having the same function. In the course of subsequent evolution, they diverge, so that the products they code for have different but related functions, with the genes still being adjacent on the chromosome. This may happen repeatedly. The process was described by Susumu Ohno in his book Evolution by Gene Duplication (1970).[3] In his book, Ohno contended that the origin of new genes during evolution was dependent on gene duplication. If only a single copy of a gene existed in the genome of a species, the proteins transcribed from this gene would be essential to their survival. These single copies of genes were considered essential. Because there was only a single copy of the gene, they could not undergo mutations which would potentially result in new genes; however, gene duplication allows essential genes to undergo mutations in the duplicated copy, which would ultimately give rise to new genes over the course of evolution.[4] Ohno argued that the mutations in the duplicated copy were tolerated because the original copy contained genetic information for the essential gene's function. Thus, species who have gene clusters have a selective evolutionary advantage.[1] Ohno contended that over a short span of time, the new genetic information exhibited by the duplicated copy of the essential gene would not serve a practical advantage; however, over a long, evolutionary time period, the genetic information in the duplicated copy may undergo additional and drastic mutations in which the proteins of the duplicated gene served a different role than those of the original essential gene.[5] Over the long, evolutionary time period, the two similar genes would diverge so the proteins of each gene were unique in their functions. Hox gene clusters, ranging in various sizes, are found among several phyla.

Hox gene clusters of various sizes are found in several phyla. Each colored box is indicative of one Hox gene.

When gene duplication occurs to produce a gene cluster, one or multiple genes may be duplicated at once. In the case of the Hox gene, a shared ancestral ProtoHox cluster was duplicated, resulting in genetic clusters in the Hox gene as well as the ParaHox gene, an evolutionary sister complex of the Hox gene.[6] It is unknown the exact number of genes contained in the duplicated Protohox cluster; however, models exist suggesting that the duplicated Protohox cluster originally contained four, three, or two genes. [7] In the case where a gene cluster is duplicated, some genes may be lost. Loss of genes is dependent of the number of genes originating in the gene cluster. In the four gene model, the ProtoHox cluster contained four genes which resulted in two twin clusters: the Hox cluster and the ParaHox cluster.[6] As its name indicates, the two gene model gave rise to the Hox cluster and the ParaHox cluster as a result of the ProtHox cluster which contained only two genes. [7] The three gene model was originally proposed in conjunction with the four gene model[7]; however, rather than the Hox cluster and the ParaHox cluster resulting from a cluster containing three genes, the Hox cluster and ParaHox cluster were as a result of single gene tandem duplication, identical genes found adjacent on the same chromosome.[6] This was independent of duplication of the ancestral ProtoHox cluster.

Intrachromosomal duplication is the duplication of genes within the same chromosome over the course of evolution (a-1). Mutations may occur in the duplicated copy, such as observed with the substitution of Guanine with Adenine (a-2). Alignment of DNA sequences exhibits homology between the two chromosomes (a-3). All segments were duplicated from the same ancestral DNA sequence as observed by the comparisons in b(i-iii).

Gene duplication may occur via cis-duplication or trans duplication.Cis-duplication, or intrachromosomal duplication, entails the duplication of genes on within the same chromosome whereas trans duplication, or interchromosomal duplication, consists of duplicating genes on neighboring but separate chromosomes.[6] The formation of the Hox cluster and the ParaHox cluster were a result of intrachromosomal duplication despite it was initially thought to be interchromosomal.[7]

Gene clusters vs. tandem repeats[edit]

Repeated genes can occur in two major patterns. Both gene clusters and tandem arrays can consist of genes that have either identical or similar functions. The repeated genes in gene clusters are dispersed randomly. However they are normally within, at most, a few thousand bases of each other. The distance between them can vary and the DNA found between each repeated gene in the cluster is non-conserved.

Tandem arrays are a group of genes with the same or similar function that are repeated consecutively without space between each gene. The genes are organized in the same orientation. In gene clusters, the repeated genes can be inverted at random.[8]

Types of gene clusters: Prokaryotic gene clusters vs. Eukaryotic gene clusters[edit]

Gene clusters may be similar to that of an operon in which all genes are controlled by a single promoter and are transcribed as a polycistronic messenger RNA. Operon-like gene clusters are primarily, but not exclusively, formed by horizontal gene transfer in prokaryotes.[9] Operon-like gene clusters have been observed in the bacterium Caenorhabditis elegans[1] as well as Escherichia coli.[9] The lac operon of Escherichia coli is the most well-studied operon-like gene cluster.[10] However, gene clusters found in Caenorhabditis elegans and Ciona intestinalis are thought to exhibit the most characteristics of a true operon.[9]

Gene clusters have also been observed in eukaryotic organisms, such as yeast, fungi, insects, vertebrates, and plants. A variety of well-known gene clusters, such as the clusters DAL and GAL, are exhibited in yeast.[1] Filamentous fungal gene clusters play a key role in the biosynthesis of primary or secondary metabolites.[9] Metabolic pathway gene clusters vastly differ from the structure of operon-like gene clusters.[1] In general, eukaryotic gene clusters greatly differ from prokaryotic gene clusters. While prokaryotic gene clusters are thought to form as a result of horizontal gene transfer, this mechanism is highly unlikely in eukaryotes. Despite the isolated observations of fungal gene clusters arising as a result of horizontal gene transfer the messenger RNA of eukaryotic gene clusters is transcribed as an independent, or monocistronic, messenger RNA.[9]


The use of bioinformatics tools and techniques can help identify gene clusters in organisms. Searching a genome (or a section of a genome) for gene clusters can be based on sequence similarity or functional similarity. For the former, common genomic analysis tools like BLAST can be used to find similar sequences throughout the genome. A program called DAVID (Database for Annotation, Visualization, and Integrated Discovery) can be applied to find functionally similar genes across the genome, once a gene of interest has been identified.[11]

See also[edit]


  1. ^ a b c d e f Yi, Gangman; Sing-Hoi Sze, Michael Thon (2007). "iIdentifying clusters in functionally related genes in genomes". Bioinformatics 23 (9): 1053–1060. doi:10.1093/bioinformatics/btl673. 
  2. ^ Michalak, P. (2008). "Coexpression, coregulation, and cofunctionality of neighboring genes in eukaryotic genomes". Genomics 91 (3): 243–248. PMID 18082363. 
  3. ^ Susumu Ohno (1970). Evolution by gene duplication. Springer-Verlag. ISBN 0-04-575015-7. 
  4. ^ Klug, William; Michael Cummings, Charlotte Spencer, Michael Palladino (2009). "Chromosome Mutations: Variation in chromosome number and arrangement". In Beth WIlbur. Concepts of Genetics (9 ed.). San Francisco, CA: Pearson Benjamin Cummings. pp. 213–214. ISBN 9780321540980. 
  5. ^ Klug, William; Michael Cummings, Charlotte Spencer, Michael Palladino (2009). "Chromosome Mutations: Variation in chromosome number and arrangement". In Beth WIlbur. Concepts of Genetics (9 ed.). San Francisco, CA: Pearson Benjamin Cummings. pp. 213–214. ISBN 9780321540980. 
  6. ^ a b c d Garcia-Fernàndez, J. (2005). "Hox, ParaHox, ProtoHox: facts and guesses". Heredity 94: 145–152. doi:10.1038/sj.hdy.6800621. 
  7. ^ a b c d Garcia-Fernàndez, Jordi (2005). "The genesis and evolution of homeobox gene clusters". Nature Reviews Genetics 6: 881–892. doi:10.1038/nrg1723. 
  8. ^ Graham, Geoffrey J. (July 1995). "Tandem genes and clustered genes". Journal of Theoretical Biology 175 (1): 71–87. doi:10.1006/jtbi.1995.0122. 
  9. ^ a b c d e Boycheva, Svetlana; Laurent Daviet, Jean-Luc Wolfender, Teresa B. Fitzpatrick (2014). "The rise of operon-like gene clusters in plants". Trends in Plant Science. doi:10.1016/j.tplants.2014.01.013. 
  10. ^ Ralston, A (2008). "Operons and Prokaryotic Gene Regulation". Nature Education 1 (1): 216. 
  11. ^  Missing or empty |title= (help)