Coevolution between simple sequence repeats (SSRs) and virus genome size
© Zhao et al.; licensee BioMed Central Ltd. 2012
Received: 18 April 2012
Accepted: 18 August 2012
Published: 30 August 2012
Relationship between the level of repetitiveness in genomic sequence and genome size has been investigated by making use of complete prokaryotic and eukaryotic genomes, but relevant studies have been rarely made in virus genomes.
In this study, a total of 257 viruses were examined, which cover 90% of genera. The results showed that simple sequence repeats (SSRs) is strongly, positively and significantly correlated with genome size. Certain repeat class is distributed in a certain range of genome sequence length. Mono-, di- and tri- repeats are widely distributed in all virus genomes, tetra- SSRs as a common component consist in genomes which more than 100 kb in size; in the range of genome < 100 kb, genomes containing penta- and hexa- SSRs are not more than 50%. Principal components analysis (PCA) indicated that dinucleotide repeat affects the differences of SSRs most strongly among virus genomes. Results showed that SSRs tend to accumulate in larger virus genomes; and the longer genome sequence, the longer repeat units.
We conducted this research standing on the height of the whole virus. We concluded that genome size is an important factor in affecting the occurrence of SSRs; hosts are also responsible for the variances of SSRs content to a certain degree.
KeywordsSimple sequence repeats Microsatellite Genome size Virus genomes Evolution
Viruses are small infectious agents, which are found wherever there is a life and have probably existed since living cells first evolved[1, 2]. There are millions of virus types. Wherein, those virus species which have been reported were sorted into dsDNA, ssDNA, dsDNA-RT, ssRNA-RT, dsRNA, (−)ssRNA and (+)ssRNA viruses based on their genome types; they can also be sorted into algae, archaea, bacteria, fungi, invertebrates, plants, protozoa and vertebrates viruses based on the general host categories according to the ICTV (International Committee on the Taxonomy of Viruses). These viruses can infect all types of organisms including archaea, bacteria, plants and animals. Many common human diseases are caused by viruses, such as common cold, influenza, chickenpox, cold scores, etc. In addition, many serious diseases such as ebola, AIDS, avian influenza and SARS are also caused by viruses. What's more, many genotypes of viruses are responsible for cancers, for example, human papillomavirus, hepatitis B virus, hepatitis C virus, Epstein-Barr virus, Kaposi's sarcoma-associated herpesvirus and human T-lymphotropic virus, and so on (http://en.wikipedia.org/wiki/Virus). Though there are three main theories on the origin of virus: regressive, cellular and coevolution origin theory, it is still unclear how viruses originated because they do not like other organisms forming fossils[6, 7]. So studying viruses via molecular information has been the most useful means in investigating how they arose and evolved[6, 8–10]. Success of viral genome researches will promote our understandings and solutions of numerous problems, including their origin, evolution, infection mechanism, disease treatment, etc. The genome sizes (defined as haploid DNA content) of viruses vary greatly between species. The smallest viral genomes — the ssDNA circoviruses, family Circoviridae — code for only two proteins and have a genome size of only 2 kb; the largest — miniviruses have genome sizes of over 1.2 Mb and code for over one thousand proteins[11, 12]. Two main mechanisms have been implicated in changes of genome size: one is the accumulation of transposable elements[13, 14]; the other is the accumulation of tandemly repetitive sequences.
Simple sequence repeats (SSRs), also known as microsatellites, generally defined as simple sequences of 1–6 nucleotides that are repeated multiple times and are present in both coding and non-coding regions of the genome[16, 17]. SSRs are ubiquitous and highly abundant in eukaryotic[18–21] and prokaryotic genomes[22, 23]. DNA repeats are primarily expanded by three models: replication, repair and recombination. Meiotic recombination plays a key role in the maintenance of sequence diversity in the human genome, and SSRs have been reported to be hot spots for recombination as well as sites for random integration[25, 26]. Thus, alterations in SSRs lie at the center of DNA evolution and sequence diversity that drives adaptation; on the other hand, changes in repetitive sequences can result in deleterious effects on gene expression and function, leading to diseases. The instability of SSRs was identified to be a pathway to lead to colorectal cancer. It is now accepted that unstable maintenance of microsatellites occurs in about 15% of sporadic colorectal cancers[28, 29]. Microsatellite instability is also frequently associated with other diseases such as ovarian cancers, malignant tumors of endometrium, small intestine, stomach, skin and brain, etc. The features of microsatellite instability observed in bacteria, yeast, mice and man can provide general clues as to how genomes evolve and how certain instability could contribute to human disease. Some pathogens use SSRs in a strategy that counteracts the host immune response by increasing the antigenic variance of the pathogen population.
Genome sequences with diverse lengths make it possible to investigate the relationship between genome size and accumulation of SSRs in all virus genera whose complete genome sequences have been reported. Therefore, scatter plots and regression analysis were performed to survey the correlation between repetitiveness (SSRs occurrence as well as SSRs length) and genome size. Distributions of different repeat classes were also surveyed among virus genomes of various sizes. While, relative abundance and relative density were examined to make the SSRs comparison parallel among differently sized species genomes; principal component analysis (PCA) was designed to investigate which repeat class(es) made a greater contribution to the variance among virus species as well as the relationships between repeat classes.
The Eighth Report of ICTV (International Committee on Taxonomy of Viruses) provided information on 3 orders, 73 families, 9 subfamilies, 287 genera and 1938 virus species; wherein 257 genera have been reported on complete genome sequences on NCBI and one typical species was identified as the representative for each genus according to the Listing in Taxonomic Order (http://ictvdb.bio-mirror.cn/Ictv/index.htm). Therefore, the 257 genome sequences were selected as samples for the analysis of relationship between SSRs distribution and genome size in the level of the whole virus. All the genome sequences were downloaded in both Genbank and FASTA formats from the NCBI (ftp://ncbi.nlm.nih.gov/genbank/). Sequences obtained include DNA and RNA, so both T and U bases were represented with T. Some genomes were segmented, multipartite and consist of two or more segments with various sizes (Additional file 1).
SSRs were identified and localized using the software SSR Identification Tool (SSRIT), which identifies perfect di-, tri-, tetra-, penta- and hexanucleotide repeats. We have considered only those repeats, wherein the motif was repeated more than 3 times for further analysis. Mononucleotide repeats (with a repeat length of 6 nt) were identified using the tool IMEX (Imperfect Microsatellite Extractor), which can extract perfect microsatellites as well as imperfect microsatellites. Here we presented the data for all perfect repeat types. No distinctions between the occurrence of repeats in coding and noncoding regions were made, the rationale for this decision was that the coding regions often account for the large proportion (mean value approximately 90%); while the sequences of noncoding regions are usually very short; moreover, the overlap phenomenon is very common in virus genomes, and many of the details were presented inAdditional file 1.
Relative abundance and relative density
These total numbers have been normalized by using relative abundance and relative density of SSRs to allow the comparisons to be parallel among genome sequences with different sizes. Relative abundance was calculated by dividing the number of SSRs by kilo base pair (kb) of sequences; and relative density (bp/kb) was calculated by dividing the total sequences analyzed (kb) by the number of base pairs of sequence contributed by each SSR.
Principal Components Analysis (PCA) is a well known statistical technique which has wide ranging applications. The main goal of PCA is to reduce the dimensionality by decomposing the total variances observed in an original data set. That is to say, we use PCA method to transform a set of original variables into a set of new and uncorrelated variables. The mathematic principle of PCA method lies in coordinate conversion. Consequently, PC (principal component) is a linear combination of the original variables.
Here, Yi is the principal component, but it must meet the following conditions: (1); (2) there is no correlation between Yi and Yj (); (3) the variance of Yi is the maximum during ; (4)
Because the variance of the original variables is greater in Y 1 axis than in Y 2 axis, so a minimum of information will be lost if integrated variable Y 1 is used for replacing all original variables. Hence, Y 1 is defined as the first principal component; in contrast, the variance of variables is smaller in Y 2 axis, and it can explain minor information relative to Y 1, so Y 2 is called the second principal component.
To obtain an expansive and unbiased data set, all virus genera with complete genome sequences reported on NCBI were scanned for SSRs analysis; wherein, one typical species was selected as the representative for each genus according to the ICTVdb (http://ictvdb.bio-mirror.cn/Ictv/index.htm). Therefore, we analyzed perfect SSRs over 6 bp long, from the 257 completely sequenced virus genomes. While, the genome size varies widely, ranging from 1682 bp (S170-(−)ssRNA-31, Hepatitis delta virus, NC_001653) to 407339 bp (S42-dsDNA-42, Emiliania huxleyi virus 86, NC_007346) (Additional file 1).
Relationship between SSRs and genome size
The length of SSRs varies from 27 bp in Nodamura virus genome (S206-(+)ssRNA-36) to 26829 bp in Amsacta moorei entomopoxvirus 'L' genome (S33-dsDNA-33); and the percentage of SSRs varies from 0.59% in Nodamura virus genome (S206-(+)ssRNA-36) to 11.54% in Amsacta moorei entomopoxvirus 'L' genome (S33-dsDNA-33) (Additional file 3). Similarly, we investigated the correlation between SSRs length and genome size. Figure3 showed that the distribution of SSRs length is similar to the SSRs occurrence in differently-sized genomes, and it indicated that SSRs length is also significantly and positively correlated with the genome size to all analyzed data (R2 = 0.915, P < 0.001), to genome >30000 bp group (R2 = 0.818, P < 0.001) and to genome ≤ 30000 bp (R2 = 0.705, P < 0.001) group. Likewise, Amsacta moorei entomopoxvirus 'L' genome (S33-dsDNA-33, NC_002520) shows features out of the ordinary, with the total SSRs length of 26829 bp and SSRs percentage of 11.54%, occupying the number-one spot in length and percentage of SSRs among all analyzed virus genomes. Except that, other points float up and down the curve with a small range (Figure3). The above results indicated that genome size is an important factor in affecting repetitiveness of microsatellites in viruses.
Relationship between repeat class and genome size
Distribution of repeat classes in different ranges of genome size
G .N. R.2
G .N. R.
G .N. R.
G .N. R.
G .N. R.
G .N. R.
2 ~ 5
5 ~ 10
10 ~ 30
30 ~ 100
100 ~ 410
Relative abundance and relative density of SSRs
PCA applying to SSRs study
Loadings of variables on the first two extracted principal components
% of Variance
Y1 = 0.440X1 + 0.467X2 + 0.444X3 + 0.435X4 + 0.374X5 + 0.248X6
Y2 = −0.111X1-0.040X2-0.038X3-0.153X4-0.229X5 + 0.953X6
< 0.001 (df = 15)
All results of Kaiser-Meyer-Olkin (KMO), Bartlett's and scree test indicated that it is significantly meaningful to analyze our data using PCA (Table2). The KMO measure with the value of 0.866 is close to 1, and Bartlett's test (< 0.001) approximates to 0, and scree plot displays the "cliff" and the "screes" vividly (Additional file 10). Moreover, the correlation is strong between the original variables (Additional file 9).
Preference of SSRs
Frequency of repeat motifs (group) in all analyzed virus genomes
Repeat motif (group)
These analyses extend those in Chen et al. in three ways: firstly, by using larger sample such that these analyses cover almost all taxonomic virus genera; secondly, by making the data more comprehensive because the genome size varies greatly, ranging from 1682 bp (S170-(−)ssRNA-31, Hepatitis delta virus, NC_001653) to 407339 bp (S42-dsDNA-42, Emiliania huxleyi virus 86, NC_007346), (Additional file 1); and thirdly, by applying statistically significant methods. The above extension made it possible to investigate the relationship between repetitiveness of microsatellites and genome size more fully and deeply.
The previous analysis simply considered the correlation between microsatellites and genome size based on relatively small sample with 54 complete Hepatitis C virus (HCV) genomes, and they found that the number of SSRs is weakly correlated with genome size. We believe that Chen's result is lacking of statistical significance due to the relatively small sample size and uniform genome length. Here, the sample made up of 257 representative virus genome sequences was designed to investigate the relationship between SSRs and genome size on the level of the whole virus. The result of our data showed a very strong and significant positive relationship between the occurrence, or length of SSRs and genome size with the value of R2 = 0.919, P < 0.001 (Figure2A) and R2 = 0.915, P < 0.001 (Figure3A), respectively. That is, the longer the virus genome sequence, the more SSRs extracted. Hancock[15, 35, 36] confirmed that the simple sequence repeats were positively and significantly correlated with the genome size in both archaea and eubacteria, and SSRs accumulate preferentially in organisms with larger genomes. Moreover, there is evidence proved that short SSRs (1–4 bp length) exist in reduced genomes, but long SSRs (5–11 bp length) consist in larger genomes in prokaryotes. The overall level of repetition in genomes is related to genome size and to the degree of repetition, and the entire genome accepts simple sequences in a concerted manner when its size increases[36, 37]. A relative scarcity of repeating DNA is a major factor in causing the relatively compact size of the avian genome[38, 39]. What's more, differences in genome size account for approximately 10% of the variance in genomic repetition in archaea and eubacteria, suggesting that other factors can also play important roles. DNA structure and base-stacking determined the number and length distributions of microsatellites in vertebrate genomes over evolutionary time. Hosts are responsible for the variances of SSRs content to a certain degree. For example, with the similar genome size, viruses infecting vertebrates and invertebrates tend to be higher than viruses attacking bacteria in SSRs content, relative abundance and relative density of SSRs overall (Additional file 15). This can be explained by the following statements. Genomes of reptiles are estimated to consist of about 30-50% repeats, birds have been estimated to consist of 15-20% of repeats[40, 41], Mus musculus of 26.1%[42, 43], and 44.9% of human genome were occupied by repeats[44, 45]. While SSR tracts make up 2.4% of the E. coli genome, significantly less than vertebrates'. SSRs have been reported to be hot spots for recombination as well as sites for random integration[25, 26]. Thus, the increase of viral SSRs content is maybe due to combining partial genome sequences of hosts in the process of infecting vertebrates and invertebrates. As we know, hosts evolved a number of defense systems in response to the challenge from parasites. Meanwhile, the parasites evolved multiple counter-defense mechanism as well under the selection pressure from hosts. Bacteria have developed CRISPR/Cas (CRISPR, Clustered regularly interspaced short palindromic repeats; Cas, CRISPR-associated) immune system to defend against bacteriophages by cleaving their DNA. Antagonistic coevolution between bacteria and their ubiquitous parasites, bacteriophage (phage), is well known[48, 49]. The genomic regions of CRISPR/Cas are hot spot of recombination, and CRISPR/Cas modules underwent rapid evolution in natural environments because of recurrent selection pressure exerted by coevolving viruses. Meanwhile, viruses may combine partial CRISPR/Cas sequence in response to the counter-defense of bacteria. Therefore, it is no coincidence that SSRs content is high in both viruses that infect vertebrates and invertebrates and these hosts themselves. The recombination enhanced the virus's ability of infection and anti-immunity to a certain extent. Evolutionarily speaking, it is the result of selection in the process of interaction between viruses and hosts. It has proposed that reduced genome size represents an adaptation to the high rate of oxidative metabolism in birds, which results primarily from the demands of flight, and the relatively small genome size of birds in general may reflect the selective pressure to minimize the amount of repetitive DNA[51, 52].
Overall, the longer genome sequence, the stronger capability the genome holding long SSRs. Each type of repeat unit is distributed in a certain length range of genomes. Mono- and di- SSRs were observed in almost all analyzed virus genomes; tri- repeats appeared to widely distribute in all virus genomes but it's number is obviously less than mono- and di- SSRs; tetra- SSRs as a common component consist in genomes with size more than 100 kb (94.4% of the genomes contain tetra- SSRs in group of genome > 100 kb). In contrast, it is relatively rare in genomes with the size < 100 kb; genomes containing penta- and hexa- SSRs are not more than 50% in < 100 kb group. Moreover, the number of tetra-, penta- and hexa- SSRs is very small (Table1). Dinucleotide and trinucleotide SSRs were observed in all analyzed HIV genomes (genome size approximately 9 kb), but almost no tetra-, penta- and hexanucleotide SSRs were found. Tetranucleotide SSRs are contained in 26.7% of the analyzed Potyvirus genomes (genome size approximately 10 kb), but the number of tetranucleotide SSRs is small. The data of tetra-, penta- and hexanucleotide SSRs are also rare in Mycoplasma, but they are relatively sufficient in bacterial[46, 55], fungal, plant, vertebrates[39, 41] and human[58, 59]. Those results confirmed that SSRs distribution is closely related to the genome size, indeed. The accumulation of simple sequence repeats would be attributed to the results of selection in the process of evolution. It has been well known that viruses such as influenza virus, hepatitis virus and human immunodeficiency virus (HIV) have a higher mutation rate to resist drugs, vaccines and so on during the process of replication and (or) recombination, which is one of the reasons for curing flu, hepatitis and acquired immunodeficiency syndrome (AIDS) with difficulty. Moreover, viruses lack complete repair mechanisms. Therefore, long SSRs can be poorly found in viruses. In the opinion of Mrázek et al., small genomes have a strong negative selection against long SSRs due to their strong constraints against expansion.
Genome size is an important factor in affecting the occurrence and the total length of SSRs, moreover, there is a positive correlation between them. Additionally, hosts are also responsible for the variances of SSRs content to a certain degree. For example, with similar genome sizes, viruses infecting vertebrates and invertebrates tend to be higher than viruses attacking bacteria in SSRs content, relative abundance and relative density of SSRs, overall. We inferred that maybe viruses combined partial genome sequences of hosts in infecting, resulting in relative large genome and high content of SSRs. Evolutionarily speaking, it is the result of selection in the process of interaction between viruses and hosts. Virus is a group of parasite, so studying of SSRs in viruses is helpful to the research of many etiopathogenesis of its hosts.
Xiangyan Zhao, Yonglei Tian, both authors contributed equally to this work.
We would like to thank Chuansheng He for the language editing and 3 anonymous reviewers for constructive comments on the earlier version of the manuscript. This work was supported by the AQSIQ Scientific Program of China [2007IK255]; National Scientific and Technique Program of China [2006BAD08A13]; Hunan Scientific Program of China [2008CKI3070] and Changsha Scientific Program of China [2011 K1113021/11].
- Gao L, Qi J: Whole genome molecular phylogeny of large dsDNA viruses using composition vector method. BMC Evol Biol. 2007, 7: 41-10.1186/1471-2148-7-4.PubMed CentralView ArticlePubMed
- Iyer LM, Balaji S, Koonin EV, Aravind L: Evolutionary genomics of nucleo-cytoplasmic large DNA viruses. Virus Res. 2006, 117: 156-184. 10.1016/j.virusres.2006.01.009.View ArticlePubMed
- Breitbart M, Rohwer F: Here a virus, there a virus, everywhere the same virus?. Trends Microbiol. 2005, 13: 278-284. 10.1016/j.tim.2005.04.003.View ArticlePubMed
- Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA: Virus Taxonomy, VIIIth Report of the ICTV. 2005, Elsevier/Academic Press, London
- Koonin EV, Senkevich TG, Dolja VV: The ancient Virus World and evolution of cells. 2006, 1: 29-doi:10.1186/1745-6150-1-29.
- Holland J, Spindler K, Horodyski F, Grabau E, Nichol S, VandePol S: Rapid evolution of RNA genomes. Science. 1982, 215: 1577-1585. 10.1126/science.7041255.View ArticlePubMed
- Holmes EC: The evolution of viral emergence. Proc Natl Acad Sci USA. 2006, 103: 4803-4804. 10.1073/pnas.0601166103.PubMed CentralView ArticlePubMed
- Domingo E: Viruses at the edge of adaptation. Virology. 2000, 270: 251-253. 10.1006/viro.2000.0320.View ArticlePubMed
- Elena SF, Lenski RE: Evolution experiments with microorganisms: the dynamics and genetic bases of adaptation. Nat Rev Genet. 2003, 4: 457-469.View ArticlePubMed
- Sanjuán R, Nebot MR, Chirico N, Mansky LM, Belshaw R: Viral mutation rates. J Virol. 2010, 84: 9733-9748. 10.1128/JVI.00694-10.PubMed CentralView ArticlePubMed
- Mrázek J, Karlin S: Distinctive features of large complex virus genomes and proteomes. Proc Natl Acad Sci USA. 2007, 104: 5127-5132. 10.1073/pnas.0700429104.PubMed CentralView ArticlePubMed
- Van Etten JL, Lane LC, Dunigan DD: DNA Viruses: The Really Big Ones (Giruses). Annu Rev Microbiol. 2010, 64: 83-99. 10.1146/annurev.micro.112408.134338.PubMed CentralView ArticlePubMed
- Bennetzen JL: Transposable element contributions to plant gene and genome evolution. Plant Mol Biol. 2000, 42: 251-269. 10.1023/A:1006344508454.View ArticlePubMed
- International Human Genome Sequencing Consortium: Initial sequencing and analysis of the human genome. Nature. 2001, 409: 860-921. 10.1038/35057062.View Article
- Hancock JM: Genome size and the accumulation of simple sequence repeats: implications of new data from genome sequencing projects. Genetica. 2002, 115: 93-103. 10.1023/A:1016028332006.View ArticlePubMed
- Li YC, Korol AB, Fahima T, Nevo E: Microsatellites within genes: structure, function, and evolution. Mol Biol Evol. 2004, 21: 991-1007. 10.1093/molbev/msh073.View ArticlePubMed
- Kovtun IV, McMurray CT: Features of trinucleotide repeat instability in vivo. Cell Res. 2008, 18: 198-213. 10.1038/cr.2008.5.View ArticlePubMed
- Bacolla A, Larson JE, Collins JR, Li J, Milosavljevic A, Stenson PD, Cooper DN, Wells RD: Abundance and length of simple repeats in vertebrate genomes are determined by their structural properties. Genome Res. 2008, 18: 1545-1553. 10.1101/gr.078303.108.PubMed CentralView ArticlePubMed
- Rajendrakumar P, Biswal AK, Balachandran SM, Srinivasarao K, Sundaram RM: Simple sequence repeats in organellar genomes of rice: frequency and distribution in genic and intergenic regions. Bioinformatics. 2007, 23: 1-4. 10.1093/bioinformatics/btl547.View ArticlePubMed
- Sharma PC, Grover A, Kahl G: Mining microsatellites in eukaryotic genomes. Trends Biotechnol. 2007, 25: 490-498. 10.1016/j.tibtech.2007.07.013.View ArticlePubMed
- Temnykh S, DeClerck G, Lukashova A, Lipovich L, Cartinhour S, McCouch S: Computational and experimental analysis of microsatellites in rice (Oryza sativa L.): frequency, length variation, transposon associations, and genetic marker potential. Genome Res. 2001, 11: 1441-1452. 10.1101/gr.184001.PubMed CentralView ArticlePubMed
- Mrázek J: Analysis of distribution indicates diverse functions of simple sequence repeats in mycoplasma genomes. Mol Biol Evol. 2006, 23: 1370-1385. 10.1093/molbev/msk023.View ArticlePubMed
- Mrázek J, Guo X, Shah A: Simple sequence repeats in prokaryotic genomes. Proc Natl Acad Sci USA. 2007, 104: 8472-8477. 10.1073/pnas.0702412104.PubMed CentralView ArticlePubMed
- Mirkin SM: Expandable DNA repeats and human disease. Nature. 2007, 447: 932-940. 10.1038/nature05977.View ArticlePubMed
- Jeffreys AJ, Holloway JK, Kauppi L, May CA, Neumann R, Slingsby MT, Webb AJ: Meiotic recombination hot spots and human DNA diversity. Philos Trans R Soc Lond B Biol Sci. 2004, 359: 141-152. 10.1098/rstb.2003.1372.PubMed CentralView ArticlePubMed
- Yant SR, Wu X, Huang Y, Garrison B, Burgess SM, Kay MA: High-resolution genome-wide mapping of transposon integration in mammals. Mol Cell Biol. 2005, 6: 2085-2094.View Article
- Söreide K, Janssen EAM, Söiland H, Körner H, Baak JPA: Microsatellite instability in colorectal cancer. Brit J Surg. 2006, 93: 395-406. 10.1002/bjs.5328.View ArticlePubMed
- Chan TL, Yuen ST, Kong CK, Chan YW, Chan AS, Ng WF, Tsui WY, Lo MW, Tam WY, Li VS, Leung SY: Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer. Nat Genet. 2006, 38: 1178-1183. 10.1038/ng1866.View ArticlePubMed
- Suter CM, Martin DIK, Ward RL: Germline epimutation of MLH1 in individuals with multiple cancers. Nat Genet. 2004, 36: 497-501. 10.1038/ng1342.View ArticlePubMed
- Wijnen J, de Leeuw W, Vasen H, van der Klift H, Møller P, Stormorken A, Meijers-Heijboer H, Lindhout D, Menko F, Vossen S, et al: Familial endometrial cancer in female carriers of MSH6 germline mutations. Nat Genet. 1999, 23: 142-144. 10.1038/13773.View ArticlePubMed
- Bacani J, Zwingerman R, Nicola DN, Spencer S, Wegrynowski T, Mitchell K, Hay K, Redston M, Holowaty E, Huntsmanet D: Tumor microsatellite instability in early onset gastric cancer. J Mol Diagn. 2005, 7: 465-477. 10.1016/S1525-1578(10)60577-6.PubMed CentralView ArticlePubMed
- Castiglia D, Pagani E, Alvino E, Vernole P, Marra G, Cannavò E, Jiricny J, Zambruno G, D'Atri S: Biallelic somatic inactivation of the mismatch repair gene MLH1 in a primary skin melanoma. Gene Chromosome Canc. 2003, 37: 165-175. 10.1002/gcc.10193.View Article
- Rocha EPC: An appraisal of the potential for illegitimate recombination in bacterial genomes and its consequences: from duplications to genome reduction. Genome Res. 2003, 13: 1123-1132. 10.1101/gr.966203.PubMed CentralView ArticlePubMed
- Chen M, Tan Z, Zeng G: Microsatellite is an important component of complete Hepatitis C virus genomes. Infect Genet Evol. 2011, 11: 1646-1654. 10.1016/j.meegid.2011.06.012.View ArticlePubMed
- Hancock JM: The contribution of slippage-like processes to genome evolution. J Mol Evol. 1995, 41: 1038-1047.View ArticlePubMed
- Hancock JM: Simple sequences in a 'minimal' genome. Nat Genet. 1996, 14: 14-15. 10.1038/ng0996-14.View ArticlePubMed
- Hancock JM: Simple sequences and the expanding genome. BioEssays. 1996, 18: 421-425. 10.1002/bies.950180512.View ArticlePubMed
- Hughes AL, Piontkivska H: DNA repeat arrays in chicken and human genomes and the adaptive evolution of avian genome size. BMC Evol Biol. 2005, 5: 12-10.1186/1471-2148-5-12.PubMed CentralView ArticlePubMed
- Wicker T, Robertson JS, Schulze SR, Feltus FA, Magrini V, Morrison JA, Mardis ER, Wilson RK, Peterson DG, Paterson AH, et al: The repetitive landscape of the chicken genome. Genome Res. 2005, 15: 126-136. 10.1101/gr.2438005.PubMed CentralView ArticlePubMed
- Epplen JT, Leipoldt M, Engel W, Schmidtke J: DNA sequence organization in avian genomes. Chromosoma. 1978, 69: 307-321. 10.1007/BF00332134.View ArticlePubMed
- Brandström M, Ellegren H: Genome-wide analysis of microsatellite polymorphism in chicken circumventing the ascertainment bias. Genome Res. 2008, 18: 881-887. 10.1101/gr.075242.107.PubMed CentralView ArticlePubMed
- Waterston RH, Lindblad-Toh K, Birney E, et al: Initial sequencing and comparative analysis of the mouse genome. Nature. 2002, 420: 520-562. 10.1038/nature01262.View ArticlePubMed
- MGSC genome assembly release 3. ftp://ftp.ncbi.nih.gov/genomes/M_musculus/ARCHIVE/MGSCv3_Release3/Assembled_Chromosomes
- Warburton PE, Hasson D, Guillem F, Lescale C, Jin X, Abrusan G: Analysis of the largest tandemly repeated DNA families in the human genome. BMC genomics. 2008, 9: 533-10.1186/1471-2164-9-533.PubMed CentralView ArticlePubMed
- Ames D, Murphy N, Helentjaris T, Sun N, Chandler V: Comparative analyses of human single- and multilocus tandem repeats. Genetics. 2008, 179: 1693-1704. 10.1534/genetics.108.087882.PubMed CentralView ArticlePubMed
- Gur-Arie R, Cohen CJ, Eitan Y, Shelef L, Hallerman EM, Kashi Y: Simple sequence repeats in Escherichia coli: abundance, distribution, composition, and polymorphism. Genome Res. 2000, 10: 62-71.PubMed CentralPubMed
- Garneau JE, Dupuis M-È, Villion M, Romero DA, Barrangou R, Boyaval P, Fremaux C, Horvath P, Magadán AH, Moineau S: The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Nature. 2010, 468: 67-72. 10.1038/nature09523.View ArticlePubMed
- Gómez P, Buckling A: Bacteria-phage antagonistic coevolution in soil. Science. 2011, 332: 106-109. 10.1126/science.1198767.View ArticlePubMed
- Pal C, Maciá MD, Oliver A, Schachar I, Buckling A: Coevolution with viruses drives the evolution of bacterial mutation rates. Nature. 2007, 450: 1079-1081. 10.1038/nature06350.View ArticlePubMed
- Takeuchi N, Wolf YI, Makarova KS, Koonin EV: Nature and Intensity of Selection Pressure on CRISPR-Associated Genes. J Bacteriol. 2012, 194: 1216-1225. 10.1128/JB.06521-11.PubMed CentralView ArticlePubMed
- Gregory TR: A bird's-eye view of the C-value enigma: Genome size, cell size, and metabolic rate in the class Aves. Evolution. 2002, 56: 121-130.View ArticlePubMed
- Szarski H: Cell size and nuclear DNA content in vertebrates. Int Rev Cytol. 1976, 44: 93-111.View ArticlePubMed
- Chen M, Tan Z, Jiang J, Li M, Chen H, Shen G, Yu R: Similar distribution of simple sequence repeats in diverse completed Human Immunodeficiency Virus Type 1 genomes. FEBS Lett. 2009, 583: 2959-2963. 10.1016/j.febslet.2009.08.004.View ArticlePubMed
- Zhao X, Tan Z, Feng H, Yang R, Li M, Jiang J, Shen G, Yu R: Microsatellites in different Potyvirus genomes: Survey and analysis. Gene. 2011, 488: 52-56. 10.1016/j.gene.2011.08.016.View ArticlePubMed
- Chen M, Zeng G, Tan Z, Jiang M, Zhang J, Zhang C, Lu L, Lin Y, Peng J: Compound microsatellites in complete Escherichia coli genomes. FEBS Lett. 2011, 585: 1072-1076. 10.1016/j.febslet.2011.03.005.View ArticlePubMed
- Karaoglu H, Lee CM, Meyer W: Survey of simple sequence repeats in completed fungal genomes. Mol Biol Evol. 2005, 22: 639-649.View ArticlePubMed
- Hong CP, Piao ZY, Kang TW, Batley J, Yang TJ, Hur YK, Bhak J, Park BS, Edwards D, Lim YP: Genomic Distribution of Simple Sequence Repeats in Brassica rapa. Mol Cells. 2007, 23: 349-356.PubMed
- Kelkar YD, Tyekucheva S, Chiaromonte F, Makova KD: The genome-wide determinants of human and chimpanzee microsatellite evolution. Genome Res. 2008, 18: 30-38.PubMed CentralView ArticlePubMed
- Mayer C, Leese F, Tollrian R: Genome-wide analysis of tandem repeats in Daphnia pulex–a comparative approach. BMC genomics. 2010, 11: 277-10.1186/1471-2164-11-277.PubMed CentralView ArticlePubMed
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