Colon cancer associated genes exhibit signatures of positive selection at functionally significant positions

BMC Evolutionary Biology

Mary J O’Connell²  Heather J Ruskin³  Christine E Loscher¹  Mark Lynch¹  Thomas A Walsh²  Andrew Webb²  Kabita Shakya³  Claire C Morgan² 

[1] Immunomodulatory Research Group, School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland;Centre for Scientific Computing & Complex Systems Modelling (SCI-SYM), Dublin City University, Glasnevin, Dublin 9, Ireland;School of Computing, Dublin City University, Glasnevin, Dublin 9, Ireland

关键词: Evolutionary medicine;    Selective pressure;    Protein functional shift;    Adaptive evolution;    Colon cancer;    Positive selection;   

Others  :  1140880
DOI  :  10.1186/1471-2148-12-114

 received in 2012-02-01, accepted in 2012-06-22,  发布年份 2012

【 摘 要 】

Background

Cancer, much like most human disease, is routinely studied by utilizing model organisms. Of these model organisms, mice are often dominant. However, our assumptions of functional equivalence fail to consider the opportunity for divergence conferred by ~180 Million Years (MY) of independent evolution between these species. For a given set of human disease related genes, it is therefore important to determine if functional equivalency has been retained between species. In this study we test the hypothesis that cancer associated genes have different patterns of substitution akin to adaptive evolution in different mammal lineages.

Results

Our analysis of the current literature and colon cancer databases identified 22 genes exhibiting colon cancer associated germline mutations. We identified orthologs for these 22 genes across a set of high coverage (>6X) vertebrate genomes. Analysis of these orthologous datasets revealed significant levels of positive selection. Evidence of lineage-specific positive selection was identified in 14 genes in both ancestral and extant lineages. Lineage-specific positive selection was detected in the ancestral Euarchontoglires and Hominidae lineages for STK11, in the ancestral primate lineage for CDH1, in the ancestral Murinae lineage for both SDHC and MSH6 genes and the ancestral Muridae lineage for TSC1.

Conclusion

Identifying positive selection in the Primate, Hominidae, Muridae and Murinae lineages suggests an ancestral functional shift in these genes between the rodent and primate lineages. Analyses such as this, combining evolutionary theory and predictions - along with medically relevant data, can thus provide us with important clues for modeling human diseases.

【 授权许可】

   
2012 Morgan et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Waterston RH, Lindblad-Toh K, et al.: Initial sequencing and comparative analysis of the mouse genome. Nature 2002, 420(6915):520-562.
• [2]Benton MJ, Donoghue PC: Paleontological evidence to date the tree of life. Mol Biol Evol 2007, 24(1):26-53.
• [3]Hirano R, Interthal H, et al.: Spinocerebellar ataxia with axonal neuropathy: consequence of a Tdp1 recessive neomorphic mutation? EMBO J 2007, 26(22):4732-4743.
• [4]Gao L, Zhang J: Why are some human disease-associated mutations fixed in mice? Trends Genet 2003, 19(12):678-681.
• [5]Hakem R, de la Pompa JL, et al.: The tumor suppressor gene Brca1 is required for embryonic cellular proliferation in the mouse. Cell 1996, 85(7):1009-1023.
• [6]MacColl AD: The ecological causes of evolution. Trends Ecol Evol 2011, 26(10):514-522.
• [7]Arbiza L, Dopazo J, et al.: Positive selection, relaxation, and acceleration in the evolution of the human and chimp genome. PLoS Comput Biol 2006, 2(4):e38.
• [8]Kosiol C, Vinar T, et al.: Patterns of positive selection in six Mammalian genomes. PLoS Genet 2008, 4(8):e1000144.
• [9]Yang Z: PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol 2007, 24(8):1586-1591.
• [10]Schmid K, Yang Z: The trouble with sliding windows and the selective pressure in BRCA1. PLoS One 2008, 3(11):e3746.
• [11]Bush RM: Predicting adaptive evolution. Nat Rev Genet 2001, 2(5):387-392.
• [12]Wong WS, Yang Z, et al.: Accuracy and power of statistical methods for detecting adaptive evolution in protein coding sequences and for identifying positively selected sites. Genetics 2004, 168(2):1041-1051.
• [13]Anisimova M, Nielsen R, et al.: Effect of recombination on the accuracy of the likelihood method for detecting positive selection at amino acid sites. Genetics 2003, 164(3):1229-1236.
• [14]Levasseur A, Gouret P, et al.: Tracking the connection between evolutionary and functional shifts using the fungal lipase/feruloyl esterase A family. BMC Evol Biol 2006, 6:92. BioMed Central Full Text
• [15]Moury B, Simon V: dN/dS-based methods detect positive selection linked to trade-offs between different fitness traits in the coat protein of potato virus Y. Mol Biol Evol 2011, 28(9):2707-2717.
• [16]Loughran NB, Hinde S, et al.: Functional consequence of positive selection revealed through rational mutagenesis of human myeloperoxidase. Mol Biol Evol 2012. (Published advance access March 28th 2012, page numbers not currently available):
• [17]Barat A, Ruskin HJ: A manually curated novel knowledge management system for genetic and epigenetic molecular determinants of colon cancer. Open Colorectal Cancer J 2010, 3:36-46.
• [18]Ferlay JSH, Bray F, Forman D, Mathers C, Parkin DM: GLOBOCAN 2008 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. 2008.
• [19]Strate LL, Syngal S: Hereditary colorectal cancer syndromes. Cancer Causes Control 2005, 16(3):201-213.
• [20]Kosinski J, Hinrichsen I, et al.: Identification of Lynch syndrome mutations in the MLH1-PMS2 interface that disturb dimerization and mismatch repair. Hum Mutat 2010, 31(8):975-982.
• [21]Vilar E, Gruber SB: Microsatellite instability in colorectal cancer-the stable evidence. Nat Rev Clin Oncol 2010, 7(3):153-162.
• [22]Kulesz-Martin M, Liu Y: p53 protein at the hub of cellular DNA damage response pathways through sequence-specific and non-sequence-specific DNA binding. Oxford J 2000, 22(6):9.
• [23]Tudzarova S, Colombo SL, et al.: Two ubiquitin ligases, APC/C-Cdh1 and SKP1-CUL1-F (SCF)-beta-TrCP, sequentially regulate glycolysis during the cell cycle. Proc Natl Acad Sci U S A 2011, 108(13):5278-5283.
• [24]Vogelstein B, Kinzler KW: Cancer genes and the pathways they control. Nature Medicine 2004, 10(8):789-799.
• [25]Futreal PA, Coin L, et al.: A census of human cancer genes. Nat Rev Cancer 2004, 4(3):177-183.
• [26]Hubbard T, Barker D, et al.: The Ensembl genome database project. Nucleic Acids Res 2002, 30(1):38-41.
• [27]Hubbard T, Andrews D, et al.: Ensembl 2005. Nucleic Acids Research 2005, 33:D447-D453.
• [28]Yoon KA, Ku JL, et al.: Germline mutations of E-cadherin gene in Korean familial gastric cancer patients. J Human Genet 1999, 44(3):177-180.
• [29]International Agency for Research on Cancer, Lyon, France; 2010. Available from: http://globocan.iarc.fr webcite
• [30]Chenna R, Sugawara H, et al.: Multiple sequence alignment with the Clustal series of programs. Nucleic Acids Res 2003, 31(13):3497-3500.
• [31]Larkin MA, Blackshields G, et al.: Clustal W and Clustal X version 2.0. Bioinformatics 2007, 23(21):2947-2948.
• [32]Rambaut A: Se-AL Sequence alignment editor. Oxford: Software package; 1996.
• [33]Anisimova M, Bielawski JP, et al.: Accuracy and power of the likelihood ratio test in detecting adaptive molecular evolution. Mol Biol Evol 2001, 18(8):1585-1592.
• [34]Zhang J, Nielsen R, et al.: Evaluation of an improved branch-site likelihood method for detecting positive selection at the molecular level. Mol Biol Evol 2005, 22(12):2472-2479.
• [35]Sawyer S: Statistical tests for detecting gene conversion. Mol Biol Evol 1989, 6(5):526-538.
• [36]Yang Z: PAML: a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci 1997, 13(5):555-556.
• [37]Yang Z, Wong WS, et al.: Bayes empirical bayes inference of amino acid sites under positive selection. Mol Biol Evol 2005, 22(4):1107-1118.
• [38]Murphy WJ, Eizirik E, et al.: Resolution of the early placental mammal radiation using Bayesian phylogenetics. Science 2001, 294(5550):2348-2351.
• [39]Nielsen R, Yang Z: Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene. Genetics 1998, 148(3):929-936.
• [40]Loughran NB, O'Connor B, et al.: The phylogeny of the mammalian heme peroxidases and the evolution of their diverse functions. BMC Evol Biol 2008, 8:101. BioMed Central Full Text
• [41]UniProt: Ongoing and future developments at the Universal Protein Resource. Nucleic Acids Res 2011, 39(Database issue):D214-219.
• [42]Voight BF, Kudaravalli S, et al.: A map of recent positive selection in the human genome. PLoS Biol 2006, 4(3):e72.
• [43]Boudeau J, Baas AF, et al.: MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm. EMBO J 2003, 22(19):5102-5114.
• [44]Baas AF, Boudeau J, et al.: Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD. EMBO J 2003, 22(12):3062-3072.
• [45]Hemminki A, Markie D, et al.: A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 1998, 391(6663):184-187.
• [46]Nakagawa H, Koyama K, et al.: Nine novel germline mutations of STK11 in ten families with Peutz-Jeghers syndrome. Hum Genet 1998, 103(2):168-172.
• [47]Dong SM, Kim KM, et al.: Frequent somatic mutations in serine/threonine kinase 11/Peutz-Jeghers syndrome gene in left-sided colon cancer. Cancer Res 1998, 58(17):3787-3790.
• [48]Westerman AM, Entius MM, et al.: Novel mutations in the LKB1/STK11 gene in Dutch Peutz-Jeghers families. Hum Mutat 1999, 13(6):476-481.
• [49]Berx G, Becker KF, et al.: Mutations of the human E-cadherin (CDH1) gene. Hum Mutat 1998, 12(4):226-237.
• [50]Latif F, Tory K, et al.: Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 1993, 260(5112):1317-1320.
• [51]Kolodner RD, Tytell JD, et al.: Germ-line msh6 mutations in colorectal cancer families. Cancer Res 1999, 59(20):5068-5074.
• [52]Ohmiya N, Matsumoto S, et al.: Germline and somatic mutations in hMSH6 and hMSH3 in gastrointestinal cancers of the microsatellite mutator phenotype. Gene 2001, 272(1–2):301-313.
• [53]Kariola R, Otway R, et al.: Two mismatch repair gene mutations found in a colon cancer patient–which one is pathogenic? Hum Genet 2003, 112(2):105-109.
• [54]Berends MJ, Wu Y, et al.: Molecular and clinical characteristics of MSH6 variants: an analysis of 25 index carriers of a germline variant. Am J Human Genet 2002, 70(1):26-37.
• [55]Ollila S, Dermadi Bebek D, et al.: Mechanisms of pathogenicity in human MSH2 missense mutants. Hum Mutat 2008, 29(11):1355-1363.
• [56]Tee AR, Fingar DC, et al.: Tuberous sclerosis complex-1 and −2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci U S A 2002, 99(21):13571-13576.
• [57]Kishi S, Zhou XZ, et al.: Telomeric protein Pin2/TRF1 as an important ATM target in response to double strand DNA breaks. J Biol Chem 2001, 276(31):29282-29291.
• [58]Blackwell LJ, Bjornson KP, et al.: DNA-dependent activation of the hMutSalpha ATPase. J Biol Chem 1998, 273(48):32049-32054.
• [59]Blackwell LJ, Martik D, et al.: Nucleotide-promoted release of hMutSalpha from heteroduplex DNA is consistent with an ATP-dependent translocation mechanism. J Biol Chem 1998, 273(48):32055-32062.
• [60]Wu Y, Berends MJ, et al.: A role for MLH3 in hereditary nonpolyposis colorectal cancer. Nat Genet 2001, 29(2):137-138.
• [61]Plaschke J, Kruger S, et al.: Eight novel MSH6 germline mutations in patients with familial and nonfamilial colorectal cancer selected by loss of protein expression in tumor tissue. Hum Mutat 2004, 23(3):285.
• [62]Niemann S, Muller U: Mutations in SDHC cause autosomal dominant paraganglioma, type 3. Nat Genet 2000, 26(3):268-270.
• [63]Bronner CE, Baker SM, et al.: Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 1994, 368(6468):258-261.
• [64]Pensotti V, Radice P, et al.: Mean age of tumor onset in hereditary nonpolyposis colorectal cancer (HNPCC) families correlates with the presence of mutations in DNA mismatch repair genes. Genes Chromosomes Cancer 1997, 19(3):135-142.
• [65]Kurzawski G, Suchy J, et al.: Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study). Clin Genet 2006, 69(1):40-47.
• [66]Tournier I, Vezain M, et al.: A large fraction of unclassified variants of the mismatch repair genes MLH1 and MSH2 is associated with splicing defects. Hum Mutat 2008, 29(12):1412-1424.
• [67]Kim JC, Kim HC, et al.: hMLH1 and hMSH2 mutations in families with familial clustering of gastric cancer and hereditary non-polyposis colorectal cancer. Cancer Detect Prev 2001, 25(6):503-510.
• [68]Nickerson ML, Warren MB, et al.: Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dube syndrome. Cancer Cell 2002, 2(2):157-164.
• [69]Sayed MG, Ahmed AF, et al.: Germline SMAD4 or BMPR1A mutations and phenotype of juvenile polyposis. Ann Surg Oncol 2002, 9(9):901-906.
• [70]Sjoblom T, Jones S, et al.: The consensus coding sequences of human breast and colorectal cancers. Science 2006, 314(5797):268-274.
• [71]Hahn SA, Schutte M, et al.: DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science 1996, 271(5247):350-353.
• [72]Ballester R, Marchuk D, et al.: The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins. Cell 1990, 63(4):851-859.
• [73]Tamura G, Sakata K, et al.: Inactivation of the E-cadherin gene in primary gastric carcinomas and gastric carcinoma cell lines. Jpn J Cancer Res 1996, 87(11):1153-1159.
• [74]Marambaud P, Shioi J, et al.: A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions. EMBO J 2002, 21(8):1948-1956.
• [75]Zhou F, Su J, et al.: Unglycosylation at Asn-633 made extracellular domain of E-cadherin folded incorrectly and arrested in endoplasmic reticulum, then sequentially degraded by ERAD. Glycoconj J 2008, 25(8):727-740.
• [76]Nicolaides NC, Papadopoulos N, et al.: Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature 1994, 371(6492):75-80.
• [77]Wang Q, Lasset C, et al.: Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes in 75 French kindreds with nonpolyposis colorectal cancer. Hum Genet 1999, 105(1–2):79-85.
• [78]Sacho EJ, Kadyrov FA, et al.: Direct visualization of asymmetric adenine-nucleotide-induced conformational changes in MutL alpha. Mol Cell 2008, 29(1):112-121.
• [79]Beausoleil SA, Villen J, et al.: A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol 2006, 24(10):1285-1292.
• [80]Guo A, Salomoni P, et al.: The function of PML in p53-dependent apoptosis. Nat Cell Biol 2000, 2(10):730-736.
• [81]Varley JM, McGown G, et al.: An extended Li-Fraumeni kindred with gastric carcinoma and a codon 175 mutation in TP53. J Med Genet 1995, 32(12):942-945.
• [82]Guran S, Tunca Y, et al.: Hereditary TP53 codon 292 and somatic P16INK4A codon 94 mutations in a Li-Fraumeni syndrome family. Cancer Genet Cytogenet 1999, 113(2):145-151.
• [83]An W, Kim J, et al.: Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53. Cell 2004, 117(6):735-748.
• [84]Hofmann TG, Moller A, et al.: Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2. Nat Cell Biol 2002, 4(1):1-10.
• [85]Bierne N, Eyre-Walker A: The genomic rate of adaptive amino acid substitution in Drosophila. Mol Biol Evol 2004, 21(7):1350-1360.
• [86]Fraser HB, Hirsh AE, et al.: Evolutionary rate in the protein interaction network. Science 2002, 296(5568):750-752.
• [87]Lunzer M, Golding GB, et al.: Pervasive cryptic epistasis in molecular evolution. PLoS Genet 2010, 6(10):e1001162.
• [88]Tenesa A, Navarro P, et al.: Recent human effective population size estimated from linkage disequilibrium. Genome Res 2007, 17(4):520-526.
• [89]Salcedo T, Geraldes A, et al.: Nucleotide variation in wild and inbred mice. Genetics 2007, 177(4):2277-2291.
• [90]Eyre-Walker A, Keightley PD, et al.: Quantifying the slightly deleterious mutation model of molecular evolution. Mol Biol Evol 2002, 19(12):2142-2149.
• [91]Eyre-Walker A, Keightley PD: Estimating the rate of adaptive molecular evolution in the presence of slightly deleterious mutations and population size change. Mol Biol Evol 2009, 26(9):2097-2108.