Low-complexity sequences and single amino acid repeats: Not just "junk" peptide sequences

Genome

Volumn 53, Issue 10, 2010, Pages 753-762

  Haerty, Wilfried ^a   Brian Golding, G ^a  

^a MCMASTER UNIVERSITY   (Canada)

Author keywords

Amino acid repeats; Selection; Simple sequences

Indexed keywords

PEPTIDE FRAGMENT;

AMINO ACID SEQUENCE; ANIMAL; CHEMISTRY; DNA BASE COMPOSITION; GENETIC CODE; GENETICS; HUMAN; MOLECULAR EVOLUTION; MOLECULAR GENETICS; PHYSIOLOGY; REVIEW; SEQUENCE ANALYSIS;

AMINO ACID SEQUENCE; ANIMALS; BASE COMPOSITION; EVOLUTION, MOLECULAR; GENETIC CODE; HUMANS; MOLECULAR SEQUENCE DATA; PEPTIDE FRAGMENTS; REPETITIVE SEQUENCES, AMINO ACID; SEQUENCE ANALYSIS, PROTEIN;

EUKARYOTA;

EID: 78650160996     PISSN: 08312796     EISSN: None     Source Type: Journal    
DOI: 10.1139/G10-063     Document Type: Review

References (98)

1. Alba, M.M., and Guigó, R. 2004. Comparative analysis of amino acid repeats in rodents and humans. Genome Res. 14(4): 549-554. doi:10.1101/gr. 1925704. PMID:15059995. (Pubitemid 38500225)
2. Alba, M.M., Santibáñez-Koref, M.F., and Hancock, J.M. 1999a. Conservation of polyglutamine tract size between mice and humans depends on codon interruption. Mol. Biol. Evol. 16(11): 1641-1644. PMID: 10555295.
3. Alba, M.M., Santibáñez-Koref, M.F., and Hancock, J.M. 1999b. Amino acid reiterations in yeast are overrepresented in particular classes of proteins and show evidence of a slippage-like mutational process. J. Mol. Evol. 49(6): 789-797. doi:10.1007/ PL00006601. PMID: 10594180.
4. Alba, M.M., Santibáñez-Koref, M.F., and Hancock, J.M. 2001. The comparative genomics of polyglutamine repeats: extreme differences in the codon organization of repeat-encoding regions between mammals and Drosophila. J. Mol. Evol. 52(3): 249-259. PMID: 11428462. (Pubitemid 32299607)
5. Anan, K., Yoshida, N., Kataoka, Y., Sato, M., Ichise, H., Nasu, M., and Ueda, S. 2007. Morphological change caused by loss of the taxon-specific polyalanine tract in Hoxd-13. Mol. Biol. Evol. 24(1): 281-287. doi:10.1093/molbev/ms1161. PMID: 17065594.
6. Aravind, L., Iyer, L.M., Wellems, T.E., and Miller, L.H. 2003. Plasmodium biology: genomic gleanings. Cell, 115(7): 771-785. doi:10.1016/S0092-8674(03) 01023-7. PMID:14697197.
7. Avivi, A., Albrecht, U., Oster, H., Joel, A., Beiles, A., and Nevo, E. 2001. Biological clock in total darkness: the Clock/MOP3 circadian system of the blind subterranean mole rat. Proc. Natl. Acad. Sci. U.S.A. 98(24): 13751-13756. doi:10.1073/pnas. 181484498. PMID: 11707566.
8. Bannen, R.M., Bingman, C.A., and Phillips, G.N., Jr. 2007. Effect of low-complexity regions on protein structure determination. J. Struct. Funct. Genomics, 8(4): 217-226. doi:10.1007/s10969-008-9039-6. PMID: 18302007.
9. Brock, G.J., Anderson, N.H., and Monckton, D.G. 1999. Cis-acting modifiers of expanded CAG/CTG triplet repeat expandability: associations with flanking GC content and proximity to CpG islands. Hum. Mol. Genet. 8(6): 1061-1067. doi:10.1093/hmg/8.6. 1061. PMID:10332038.
10. Brown, L.Y., and Brown, S.A. 2004. Alanine tracts: the expanding story of human illness and trinucleotide repeats. Trends Genet. 20(1): 51-58. doi:10.1016/j.tig.2003.11.002. PMID: 14698619.
11. Brown, C.J., Takayama, S., Campen, A.M., Vise, P., Marshall, T.W., Oldfield, C.J., et al. 2002. Evolutionary rate heterogeneity in proteins with long disordered regions. J. Mol. Evol. 55(1): 104-110. doi:10.1007/s00239-001- 2309-6. PMID:12165847.
12. Brown, C.J., Johnson, A.K., and Daughdrill, G.W. 2010. Comparing models of evolution for ordered and disordered proteins. Mol. Biol. Evol. 27(3): 609-621. doi:10.1093/molbev/msp277. PMID:19923193.
13. Buschiazzo, E., and Gemmell, N.J. 2006. The rise, fall and renaissance of microsatellites in eukaryotic genomes. Bioessays, 28(10): 1040-1050. doi:10.1002/bies.20470. PMID:16998838. (Pubitemid 44570453)
14. Butland, S.L., Devon, R.S., Huang, Y., Mead, C.L., Meynert, A.M., Neal, S.J., et al. 2007. CAG-encoded polyglutamine length polymorphism in the human genome. BMC Genomics, 8(1): 126. doi:10.1186/1471-2164-8-126. PMID:17519034. (Pubitemid 46995051)
15. Crick, S.L., Jayaraman, M., Frieden, C., Wetzel, R., and Pappu, R.V. 2006. Fluorescence correlation spectroscopy shows that monomeric polyglutamine molecules form collapsed structures in aqueous solutions. Proc. Natl. Acad. Sci. U.S.A. 103(45): 16764-16769. doi:10.1073/pnas.0608175103. PMID: 17075061.
16. Dalby, A.R. 2009. A comparative proteomic analysis of the simple amino acid repeat distributions in Plasmodia reveals lineage specific amino acid selection. PLoS One, 4(7): e6231. doi:10. 1371/journal.pone.0006231. PMID: 19597555.
17. Darlington, T.K., Wager-Smith, K., Ceriani, M.F., Staknis, D., Gekakis, N., Steeves, T.D.L., et al. 1998. Closing the circadian loop: CLOCK-induced transcription of its own inhibitors per and tim. Science, 280(5369): 1599-1603. doi:10.1126/science. 280.5369.1599. PMID:9616122. (Pubitemid 28277704)
18. Délot, E., King, L.M., Briggs, M.D., Wilcox, W.R., and Cohn, D.H. 1999. Trinucleotide expansion mutations in the cartilage oligomeric matrix protein (COMP) gene. Hum. Mol. Genet. 8(1): 123-128. doi:10.1093/hmg/8.1.123. PMID:9887340.
19. DePristo, M.A., Zilversmit, M.M., and Hartl, D.L. 2006. On the abundance, amino acid composition, and evolutionary dynamics of low-complexity regions in proteins. Gene, 378: 19-30. doi:10. 1016/j.gene.2006.03.023. PMID: 16806741. (Pubitemid 44108462)
20. Dion, V., Lin, Y., Hubert, L., Jr., Waterland, R.A., and Wilson, J.H. 2008. Dnmtl deficiency promotes CAG repeat expansion in the mouse germline. Hum. Mol. Genet. 17(9): 1306-1317. doi:10.1093/hmg/ddn019. PMID: 18252747.
21. Dosztányi, Z., Sándor, M., Tompa, P., and Simon, I. 2007. Prediction of protein disorder at the domain level. Curr. Protein Pept. Sci. 8(2): 161-171. doi: 10.2174/138920307780363406. PMID: 17430197.
22. Dunker, A.K., Lawson, J.D., Brown, C.J., Williams, R.M., Romero, P., Oh, J.S., et al. 2001. Intrinsically disordered protein. J. Mol. Graph. Model. 19(1): 26-59. doi:10.1016/S1093-3263(00)00138-8. PMID:11381529.
23. Dunker, A.K., Brown, C.J., Lawson, J.D., Iakoucheva, L.M., and Obradović, Z. 2002. Intrinsic disorder and protein function. Biochemistry, 41(21): 6573-6582. doi:10.1021/bi012159+. PMID: 12022860.
24. Eichinger, L., Pachebat, J.A., Glöckner, G., Rajandream, M.A., Sucgang, R., Berriman, M., et al. 2005. The genome of the social amoeba Dictyostelium discoideum. Nature, 435 (7038): 43-57. doi:10.1038/nature03481. PMID:15875012.
25. Ellegren, H. 2004. Microsatellites: simple sequences with complex evolution. Nat. Rev. Genet. 5(6): 435-445. doi:10.1038/nrg1348. PMID:15153996.
26. Faux, N.G., Bottomley, S.P., Lesk, A.M., Irving, J.A., Morrison, J.R., de la Banda, M.G., and Whisstock, J.C. 2005. Functional insights from the distribution and role of homopeptide repeatcontaining proteins. Genome Res. 15(4): 537-551. doi:10.1101/ gr.3096505. PMID: 15805494.
27. Faux, N.G., Huttley, G.A., Mahmood, K., Webb, G.I., de la Banda, M.G., and Whisstock, J.C. 2007. RCPdb: an evolutionary classification and codon usage database for repeat-containing proteins. Genome Res. 17(7): 1118-1127. doi:10.1101/gr.6255407. PMID: 17567984. (Pubitemid 47026359)
28. Fondon, J.W., III, and Garner, H.R. 2004. Molecular origins of rapid and continuous morphological evolution. Proc. Natl. Acad. Sci. U.S.A. 101(52): 18058-18063. doi:10.1073/pnas. 0408118101. PMID: 15596718.
29. Galant, R., and Carroll, S.B. 2002. Evolution of a transcriptional repression domain in an insect Hox protein. Nature, 415 (6874): 910-913. doi:10.1038/nature717. PMID:11859369. (Pubitemid 34174752)
30. Gatchel, J.R., and Zoghbi, H.Y. 2005. Diseases of unstable repeat expansion: mechanisms and common principles. Nat. Rev. Genet. 6(10): 743-755. doi:10.1038/nrg1691. PMID: 16205714.
31. Golding, G.B. 1999. Simple sequence is abundant in eukaryotic proteins. Protein Sci. 8(6): 1358-1361. doi:10.1110/ps.8.6.1358. PMID:10386886.
32. Haerty, W., and Golding, B. 2009. Similar selective factors affect both between-gene and between-exon divergence in Drosophila. Mol. Biol. Evol. 26(4): 859-866. doi:10.1093/molbev/msp006. PMID:19150804.
33. Haerty, W., and Golding, G.B. 2010. Genome-wide evidence for selection acting on single amino acid repeats. Genome Res. 20(6): 755-760. doi:10.1101/gr.101246.109. PMID:20056893.
34. Hancock, J.M., and Simon, M. 2005. Simple sequence repeats in proteins and their significance for network evolution. Gene, 345(1): 113-118. doi:10.1016/j.gene.2004.11.023. PMID: 15716087. (Pubitemid 40208507)
35. Hancock, J.M., Worthey, E.A., and Santibáñez-Koref, M.F. 2001. A role for selection in regulating the evolutionary emergence of disease-causing and other coding CAG repeats in humans and mice. Mol. Biol. Evol. 18(6): 1014-1023. PMID: 11371590.
36. Harr, B., Todorova, J., and Schlötterer, C 2002. Mismatch repairdriven mutational bias in D. melanogaster. Mol. Cell, 10(1): 199-205. doi:10.1016/S1097-2765(02)00575-0. PMID: 12150919.
37. Hoque, M., Young, T.M., Lee, .C.G., Serrero, G., Mathews, M.B., and Pe'ery, T. 2003. The growth factor granulin interacts with cyclin T1 and modulates P-TEFb-dependent transcription. Mol. Cell. Biol. 23(5): 1688-1702. doi:10.1128/MCB.23.5.1688-1702.2003. PMID:12588988.
38. Huntley, M.A., and Clark, A.G. 2007. Evolutionary analysis of amino acid repeats across the genomes of 12 Drosophila species. Mol. Biol. Evol. 24(12): 2598-2609. doi:10.1093/molbev/ msm129. PMID: 17602168.
39. Huntley, M., and Golding, G.B. 2000. Evolution of simple sequence in proteins. J. Mol. Evol. 51(2): 131-140. PMID: 10948269.
40. Huntley, M.A., and Golding, G.B. 2002. Simple sequences are rare in the Protein Data Bank. Proteins, 48(1): 134-140. doi:10.1002/ prot.10150. PMID:12012345.
41. Huntley, M.A., and Golding, G.B. 2006. Selection and slippage creating serine homopolymers. Mol. Biol. Evol. 23(11): 2017-2025. doi:10.1093/molbev/ ms1073. PMID:16877497.
42. Innis, J.W., Mortlock, D., Chen, Z., Ludwig, M., Williams, M.E., Williams, T.M., et al. 2004. Polyalanine expansion in HOXA13: three new affected families and the molecular consequences in a mouse model. Hum. Mol. Genet. 13(22): 2841-2851. doi:10.1093/hmg/ddh306. PMID: 15385446.
43. Jodice, C., Giovannone, B., Calabresi, V., Bellocchi, M., Terrenato, L., and Novelletto, A. 1997. Population variation analysis at nine loci containing expressed trinucleotide repeats. Ann. Hum. Genet. 61(Pt 5): 425-438. PMID:9459004.
44. Johnsen, A., Fidler, A.E., Kuhn, S., Carter, K.L., Hoffmann, A., Barr, I.R., et al. 2007. Avian Clock gene polymorphism: evidence for a latitudinal cline in allele frequencies. Mol. Ecol. 16(22): 4867-4880. doi:10.1111/j.1365- 294X.2007.03552.x. PMID: 17927702.
45. Karlin, S., Brocchieri, L., Bergman, A., Mrazek, J., and Gentles, A.J. 2002. Amino acid runs in eukaryotic proteomes and disease associations. Proc. Natl. Acad. Sci. U.S.A. 99(1): 333-338. doi:10.1073/pnas.012608599. PMID: 11782551.
46. Kashi, Y., and King, D.G. 2006. Simple sequence repeats as advantageous mutators in evolution. Trends Genet. 22(5): 253-259. doi:10.1016/j.tig.2006.03. 005. PMID:16567018.
47. Katti, M.V., Ranjekar, P.K., and Gupta, V.S. 2001. Differential distribution of simple sequence repeats in eukaryotic genome sequences. Mol. Biol. Evol. 18(7): 1161-1167. PMID: 11420357.
48. King, D.P., Zhao, Y., Sangoram, A.M., Wilsbacher, L.D., Tanaka, M., Antoch, M.P., et al. 1997. Positional cloning of the mouse circadian Clock gene. Cell, 89(4): 641-653. doi:10.1016/S0092-8674(00)80245-7. PMID:9160755.
49. Kruglyak, S., Durrett, R.T., Schug, M.D., and Aquadro, C.F. 1998. Equilibrium distributions of microsatellite repeat length resulting from a balance between slippage events and point mutations. Proc. Natl. Acad. Sci. U.S.A. 95(18): 10774-10778. doi:10. 1073/pnas.95.18.10774. PMID:9724780.
50. Kyriacou, C.P., Peixoto, A.A., Sandrelli, F., Costa, R., and Tauber, E. 2008. Clines in clock genes: fine-tuning circadian rhythms to the environment. Trends Genet. 24(3): 124-132. doi:10.1016/j. tig.2007.12.003. PMID: 18243399.
51. Lanz, R.B., Wieland, S., Hug, M., and Rusconi, S. 1995. A transcriptional repressor obtained by alternative translation of a trinucleotide repeat. Nucleic Acids Res. 23(1): 138-145. doi:10. 1093/nar/23.1.138. PMID:7532856.
52. Le Gall, T., Romero, P.R., Cortese, M.S., Uversky, V.N., and Dunker, A.K. 2007. Intrinsic disorder in the Protein Data Bank. J. Biomol. Struct. Dyn. 24(4): 325-342. PMID: 17206849.
53. Levinson, G., and Gutman, G.A. 1987. Slipped-strand mispairing: a major mechanism for DNA sequence evolution. Mol. Biol. Evol. 4(3): 203-221. PMID:3328815.
54. Li, Y.C., Korol, A.B., Fahima, T., and Nevo, E. 2004. Microsatellites within genes: structure, function, and evolution. Mol. Biol. Evol. 21(6): 991-1007. doi:10.1093/molbev/msh073. PMID: 14963101.
55. Libby, R.T., Hagerman, K.A., Pineda, V.V., Lau, R., Cho, D.H., Baccam, S.L., et al. 2008. CTCF cis-regulates trinucleotide repeat instability in an epigenetic manner: a novel basis for mutational hot spot determination. PLoS Genet. 4(11): e1000257. doi:10.1371/journal.pgen.1000257. PMID: 19008940.
56. Lin, Y.S., Hsu, W.L., Hwang, J.K., and Li, W.H. 2007. Proportion of solvent-exposed amino acids in a protein and rate of protein evolution. Mol. Biol. Evol. 24(4): 1005-1011. doi:10.1093/ molbev/msm019. PMID: 17264066.
57. Lindqvist, C., Laakkonen, L., and Albert, V.A. 2007. Polyglutamine variation in a flowering time protein correlates with island age in a Hawaiian plant radiation. BMC Evol. Biol. 7(1): 105. doi:10.1186/1471-2148-7-105. PMID: 17605781.
58. Lovell, S.C. 2003. Are non-functional, unfolded proteins ('junk proteins') common in the genome? FEBS Lett. 554(3): 237-239. doi:10.1016/S0014-5793(03)01223-7. PMID: 14623072.
59. Mao, A.H., Crick, S.L., Vitalis, A., Chicoine, C.L., and Pappu, R.V. 2010. Net charge per residue modulates conformational ensembles of intrinsically disordered proteins. Proc. Natl. Acad. Sci. U.S.A. 107(18): 8183-8188. doi:10.1073/pnas.0911107107. PMID:20404210.
60. Marcotte, E.M., Pellegrini, M., Yeates, T.O., and Eisenberg, D. 1999. A census of protein repeats. J. Mol. Biol. 293(1): 151-160. doi:10.1006/jmbi.1999. 3136. PMID: 10512723.
61. Michael, T.P., Park, S., Kim, T.S., Booth, J., Byer, A., Sun, Q., et al. 2007. Simple sequence repeats provide a substrate for phenotypic variation in the Neurospora crassa circadian clock. PLoS One, 2(8): e795. doi:10.1371/journal.pone.0000795. PMID: 17726525.
62. Mirkin, S.M. 2007. Expandable DNA repeats and human disease. Nature, 447(7147): 932-940. doi:10.1038/nature05977. PMID: 17581576.
63. Molla, M., Delcher, A., Sunyaev, S., Cantor, C., and Kasif, S. 2009. Triplet repeat length bias and variation in the human transcriptome. Proc. Natl. Acad. Sci. U.S.A. 106(40): 17095-17100. doi:10.1073/pnas.0907112106. PMID:19805156.
64. Mularoni, L., Guigó, R., and Albà, M.M. 2006. Mutation patterns of amino acid tandem repeats in the human proteome. Genome Biol. 7(4): R33. doi:10.1186/gb-2006-7-4-r33. PMID: 16640792. (Pubitemid 43871877)
65. Mularoni, L., Veitia, R.A., and Alba, M.M. 2007. Highly constrained proteins contain an unexpectedly large number of amino acid tandem repeats. Genomics, 89(3): 316-325. doi:10.1016/j. ygeno.2006.11.011. PMID: 17196365. (Pubitemid 46205127)
66. Mundlos, S., Otto, F., Mundlos, C., Mulliken, J.B., Aylsworth, A.S., Albright, S., et al. 1997. Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia. Cell, 89(5): 773-779. doi:10.1016/S0092-8674(00) 80260-3. PMID:9182765. (Pubitemid 27516180)
67. Nakachi, Y., Hayakawa, T., Oota, H., Sumiyama, K., Wang, L., and Ueda, S. 1997. Nucleotide compositional constraints on genomes generate alanine-, glycine-, and proline-rich structures in transcription factors. Mol. Biol. Evol. 14(10): 1042-1049. PMID:9335144.
68. O'Malley, K.G., and Banks, M.A. 2008. A latitudinal cline in the Chinook salmon (Oncorhynchus tshawytscha) Clock gene: evidence for selection on PolyQ length variants. Proc. R. Soc. B Biol. Sci. 275(1653): 2813-2821. doi:10.1098/rspb.2008.0524. PMID: 18713722.
69. Orr, H.T., and Zoghbi, H.Y. 2007. Trinucleotide repeat disorders. Annu. Rev. Neurosci. 30(1): 575-621. doi:10.1146/annurev. neuro.29.051605.113042. PMID:17417937.
70. Pearson, C.E., Edamura, K.N., and Cleary, J.D. 2005. Repeat instability: mechanisms of dynamic mutations. Nat. Rev. Genet. 6(10): 729-742. doi:10.1038/nrg1689. PMID:16205713.
71. Rolfsmeier, M.L., and Lahue, R.S. 2000. Stabilizing effects of interruptions on trinucleotide repeat expansions in Saccharomyces cerevisiae. Mol. Cell. Biol. 20(1): 173-180. doi:10.1128/MCB. 20.1.173-180.2000. PMID: 10594019.
72. Romero, P., Obradovic, Z., Li, X., Garner, E.C., Brown, C.J., and Dunker, A.K. 2001. Sequence complexity of disordered protein. Proteins, 42(1): 38-48. doi:10.1002/1097-0134(20010101) 42:1<38::AID-PROT50>3.0.CO;2-3. PMID: 11093259.
73. Romero, P.R., Zaidi, S., Fang, Y.Y., Uversky, V.N., Radivojac, P., Oldfield, C.J., et al. 2006. Alternative splicing in concert with protein intrinsic disorder enables increased functional diversity in multicellular organisms. Proc. Natl. Acad. Sci. U.S.A. 103(22): 8390-8395. doi:10.1073/pnas.0507916103. PMID: 16717195.
74. Ronshaugen, M., McGinnis, N., and McGinnis, W. 2002. Hox protein mutation and macroevolution of the insect body plan. Nature, 415(6874): 914-917. doi:10.1038/nature716. PMID: 11859370. (Pubitemid 34174753)
75. Rosato, E., Peixoto, A.A., Costa, R., and Kyriacou, C.P. 1997. Linkage disequilibrium, mutational analysis and natural selection in the repetitive region of the clock gene, period, in Drosophila melanogaster. Genet. Res. 69(2): 89-99. doi:10.1017/ S001667239700267X. PMID:10191718. (Pubitemid 27356692)
76. Salichs, E., Ledda, A., Mularoni, L., Alba, M.M., de la Luna, S., and Katsanis, N. 2009. Genome-wide analysis of histidine repeats reveals their role in the localization of human proteins to the nuclear speckles compartment. PLoS Genet. 5(3): e1000397. doi:10.1371/journal.pgen.1000397. PMID:19266028.
77. Santibáñez-Koref, M.F., Gangeswaran, R., and Hancock, J.M. 2001. A relationship between lengths of microsatellites and nearby substitution rates in mammalian genomes. Mol. Biol. Evol. 18(11): 2119-2123. PMID: 11606708.
78. Sawyer, L.A., Hennessy, J.M., Peixoto, A.A., Rosato, E., Parkinson, H., Costa, R., and Kyriacou, C.P. 1997. Natural variation in a Drosophila clock gene and temperature compensation. Science, 278(5346): 2117-2120. doi:10.1126/science.278.5346. 2117. PMID:9405346.
79. Sawyer, L.A., Sandrelli, F., Pasetto, C., Peixoto, A.A., Rosato, E., Costa, R., and Kyriacou, C.P. 2006. The period gene Thr-Gly polymorphism in Australian and African Drosophila melanogaster populations: implications for selection. Genetics, 174(1): 465-480. doi:10.1534/genetics.106.058792. PMID: 16849607.
80. Schmid, K.J., and Tautz, D. 1999. A comparison of homologous developmental genes from Drosophila and Tribolium reveals major differences in length and trinucleotide repeat content. J. Mol. Evol. 49(5): 558-566. doi:10.1007/PL00006577. PMID: 10552037.
81. Sears, K.E., Goswami, A., Flynn, J.J., and Niswander, L.A. 2007. The correlated evolution of Runx2 tandem repeats, transcriptional activity, and facial length in Carnivora. Evol. Dev. 9(6): 555-565. doi:10.1111/j.l525-142X. 2007.00196.x. PMID: 17976052.
82. II130, interfering with CREB-dependent transcription. Nat. Genet. 26(1): 29-36. doi:10.1038/79139. PMID: 10973244.
83. Sickmeier, M., Hamilton, J.A., LeGall, T., Vacic, V., Cortese, M.S., Tantos, A., et al. 2007. DisProt: the Database of Disordered Proteins. Nucleic Acids Res. 35(Database issue): D786-D793. doi:10.1093/nar/gk1893.PMID:17145717.
84. Sim, K.L., and Creamer, T.P. 2002. Abundance and distributions of eukaryote protein simple sequences. Mol. Cell. Proteomics, 1(12): 983-995. doi:10.1074/mcp.M200032-MCP200. PMID: 12543934.
85. Simon, M., and Hancock, J.M. 2009. Tandem and cryptic amino acid repeats accumulate in disordered regions of proteins. Genome Biol. 10(6): R59. doi:10.1186/gb-2009-10-6-r59. PMID: 19486509.
86. Siwach, P., Pophaly, S.D., and Ganesh, S. 2006. Genomic and evolutionary insights into genes encoding proteins with single amino acid repeats. Mol. Biol. Evol. 23(7): 1357-1369. doi:10. 1093/molbev/msk022. PMID: 16618963.
87. Slepko, N., Bhattacharyya, A.M., Jackson, G.R., Steffan, J.S., Marsh, J.L., Thompson, L.M., and Wetzel, R. 2006. Normalrepeat-length polyglutamine peptides accelerate aggregation nucleation and cytotoxicity of expanded polyglutamine proteins. Proc. Natl. Acad. Sci. U.S.A. 103(39): 14367-14372. doi:10. 1073/pnas.0602348103. PMID: 16980414.
88. Tauber, E., Roe, H., Costa, R., Hennessy, J.M., and Kyriacou, C.P. 2003. Temporal mating isolation driven by a behavioral gene in Drosophila. Curr. Biol. 13(2): 140-145. doi:10.1016/S0960-9822(03)00004-6. PMID:12546788. (Pubitemid 36154342)
89. Tompa, P. 2010. The structure and function of intrinsically disordered proteins. Chapman & Hall / CRC Press, Boca Raton, Fla.
90. Tran, H.T., Mao, A., and Pappu, R.V. 2008. Role of backbonesolvent interactions in determining conformational equilibria of intrinsically disordered proteins. J. Am. Chem. Soc. 130(23): 7380-7392. doi:10.1021/ ja710446s. PMID: 18481860.
91. Usdin, K. 2008. The biological effects of simple tandem repeats: lessons from the repeat expansion diseases. Genome Res. 18(7): 1011-1019. doi:10.1101/gr.070409.107. PMID:18593815. (Pubitemid 351931152)
92. Wang, X., Vitalis, A., Wyczalkowski, M.A., and Pappu, R.V. 2006. Characterizing the conformational ensemble of monomeric polyglutamine. Proteins, 63(2): 297-311. doi:10.1002/prot.20761. PMID: 16299774.
93. Wang, Z., Yuan, L., Rossiter, S.J., Zuo, X., Ru, B., Zhong, H., et al. 2009. Adaptive evolution of 5'HoxD genes in the origin and diversification of the cetacean flipper. Mol. Biol. Evol. 26(3): 613-622. doi:10.1093/molbev/ msn282. PMID: 19074008.
94. Ward, J.J., Sodhi, J.S., McGuffin, L.J., Buxton, B.F., and Jones, D.T. 2004. Prediction and functional analysis of native disorder in proteins from the three kingdoms of life. J. Mol. Biol. 337(3): 635-645. doi:10.1016/j.jmb.2004. 02.002. PMID:15019783.
95. Warren, S.T. 1997. Polyalanine expansion in synpolydactyly might result from unequal crossing-over of HOXD13. Science, 275(5298): 408-409. doi:10.1126/science.275.5298.408. PMID: 9005557.
96. Wootton, J.C., and Federhen, S. 1993. Statistics of local complexity in amino acid sequences and sequence databases. Comput. Chem. 17(2): 149-163. doi:10.1016/0097-8485(93)85006-X.
97. Wren, J.D., Forgacs, E., Fondon, J.W., 3rd, Pertsemlidis, A., Cheng, S.Y., Gallardo, T., et al. 2000. Repeat polymorphisms within gene regions: phenotypic and evolutionary implications. Am. J. Hum. Genet. 67(2): 345-356. doi:10.1086/303013. PMID:10889045.
98. Yu, F., Sabeti, P.C., Hardenbol, P., Fu, Q., Fry, B., Lu, X., et al. 2005. Positive selection of a pre-expansion CAG repeat of the human SCA2 gene. PLoS Genet. 1(3): e41. doi:10.1371/journal. pgen.0010041. PMID: 16205789.