Abstract
A highly variable family of related DNA sequences was examined in order to determine the effect of local sequence environment on substitution mutation; 29 sequences from the Brassica self-incompatibility gene family, which possess a high level of nonsynonymous mutations, were aligned and grouped according to their similarity and function. The level and distribution of substitution mutations were calculated. A nonrandom distribution of sequence variation was observed along the sequences. The effect of neighbor biases and structural and thermodynamic measures were then compared in the absence of strong codon conservation. Biases were observed in the rates of substitution of the same base pair in different local sequence environments. The effect of the 5′ neighbor was such that nucleotide A or C was associated with more mutations than G or T. There were significant interactions of certain dinucleotides with the frequency of mutation. Sequence-dependent measures of helical stability, intrinsic curvature, components of curvature, and stacking interactions were calculated for each sequence. Decreased helical stability was found to be associated with increased mutation. The compound measure of curvature, calculated according to the “wedge” model, showed little association with mutation. However, the components of increased wedge angle and decreased twist both showed an association with increased mutation. A small effect of A-type DNA stacking was found to be associated with mutated bases.
Similar content being viewed by others
References
Aida M (1988) An ab initio orbital study on the sequence-dependency of DNA conformation: an evaluation of intra- and inter-strand stacking interaction energy. J Theor Biol 130:327–335
Aida M, Nagata C (1986) An ab initio orbital study on the stacking interaction between nucleic acid bases: dependence on the sequence and relation to the conformation. Int J Quant Chem 29:1253–1261
Anderson MA, McFadden GI, Bernatzky R, Atkinson A, Orpin T, Dedman H, Tregear GW, Fernley R, Clarke AE (1989) Sequence variability of 3 alleles of the self-incompatibility gene of Nicotiana alata. Plant Cell 1:483–491
Benight AS, Wartell RM (1983) Influence of base-pair changes and cooperativity parameters on the melting curves of short DNAs. Biopolymers 22:1409–1425
Bernardi G, Mouchiroud D, Gautier C (1993) Silent substitutions in mammalian genomes and their evolutionary implications. J Mol Evol 37:583–589
Blake RD, Hess ST, Nicholson-Tuell J (1993) The influence of nearest neighbors on the rate and pattern of spontaneous point mutations. J Mol Evol 34:198–200
Bolshoy A, McNamara P, Harrington RE, Trifonov EN (1991) Curved DNA without A-A: experimental estimation of all 16 DNA wedge angles. Proc Natl Acad Sci USA 88:2312–2316
Chen CH, Nasrallah JB (1990) A new class of S sequence defined by pollen recessive self incompatibility allele of Brassica oleracea. Mol Gen Genet 222:241–248
Devereux J, Haeberli IP, Smithies O (1984) A comprehensive set of sequence analysis programs for the Vax. Nucleic Acids Res 12: 387–395
Doi H (1991) Importance of purine and pyrimidine content of local nucleotide sequences (six bases long) for evolution of the human immunodeficiency virus type 1. Proc Natl Acad Sci USA 88:9282–9286
Dwyer KG, Balent MA, Nasrallah JB, Nasrallah ME (1991) DNA sequences of self-incompatibility genes from Brassica campestris and Brassica oleracea—polymorphism predating speciation. Plant Mol Biol 16:481–486
Dwyer KG, Lalonde BA, Nasrallah JB, Nasrallah ME (1992) Structure and expression of AtSl, an Arabidopsis thaliana gene homologous to the S-locus related genes of Brassica. Mol Gen Genet 231:442–448
Filipski J (1988) Why the rate of silent codon substitutions is variable within a vertebrate genome. J Theor Biol 134:159–164
Fixman M, Friere JJ (1977) Theory of DNA melting curves. Biopolymers 16:2693–2704
Gotoh O, Tagashira Y (1981) Stabilities of nearest-neighbour doublets in double-helical DNA determined by fitting calculated melting profiles to observed profiles. Biopolymers 20:1033–1042
Hedrik PW, Whittam TS, Parham P (1991) Heterozygosity at individual amino acid sites: extremely high levels for HLA-A and -B genes. Proc Natl Acad Sci USA 88:5897–5901
Hughes AL, Nei M (1988) Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature 335:167–170
Ioerger TR, Clark AG, Kao TH (1990) Polymorphism at the self-incompatibility locus in solanaceae predates speciation. Proc Natl Acad Sci USA 87:9732–9735
Kabsch W, Sander S, Trifonov EN (1982) The 10 helical twist angles of B DNA. Nucleic Acids Res 10:1097–1104
Karlin S, Altshul SF (1990) Methods for assessing the statistical significance of molecular sequence features by using general scoring schemes. Proc Natl Acad Sci USA 87:2264–2268
King GJ (1993) Stability, structure and complexity of yeast chromosome Ill. Nucleic Acids Res 21:4239–4245
Levine AJ, Momand J, Finlay CA (1991) The p53 tumour suppressor gene. Nature 351:453–455
Li W-H, Luo C-C, Wu C-I (1984) Nonrandomness of point mutation as reflected in nucleotide substitutions in pseudo-genes and its evolutionary implications. J Mol Evol 21:58–71
McCullagh P, Nelder JA (1989) Generalised linear models. Chapman and Hall, London
Nasrallah JB, Kao T-H, Chen C-H, Goldberg ML, Nasrallah ME (1987) Amino acid sequence of glycoproteins encoded by three alleles of the S locus of Brassica oleracea. Nature 326:617–619
Ockendon DJ (1982) An S-allele survey of cabbage (Brassica oleracea var. capitata) Euphytica 31:325–331
Payne RW, Lane PW, Digby PGN, Harding SA, Leech PK, Morgan GW, Todd AD, Thompson R, Tunnicliffe Wilson G, Welham SJ, White RP (1993) Genstat 5 release 3 reference manual. Clarendon Press, Oxford
Shenkin PS, Erman B, Mastrandrea LD (1991) Information-theoretical entropy as a measure of sequence variability. Proteins Struct Funct Genet 11:297–313
Shpigelman ES, Trifonov EN, Bolshoy A (1993) Curvature: software for the analysis of curved DNA. Comput Appl Biosci 9:435–440
Sprent P (1993) Applied non-parametric statistical methods. Chapman and Hall, London
Stein JC, Howlett B, Boyes DC,Nasrallah ME, Nasrallah JB (1991) Molecular cloning of a putative receptor protein kinase gene encoded at the self-incompatibility locus of Brassica oleracea. Proc Natl Acad Sci USA 88:8816–8820
Ticher A, Graur D (1989) Nucleic acid composition, codon usage, and the rate of synonymous substitution in protein-coding genes. J Mol Evol 28:286–298
Trick M, Heizmann, P (1992) Sporophytic self-incompatibility systems: Brassica S-gene family. Int Rev Cytol 140:485–524
Ulanovsky LE, Trifonov EN (1987) Estimation of wedge components in curved DNA. Nature 326:720–722
Wada A, Suyama A (1986) Physico-genetic coupling of double-helix stability with gene location in DNA. Proc Int Symp Comput Anal Life Sci 17:140–150
Wolfe AP (1989) Nucleosome positioning and modification: chromatin structures that potentiate transcription. TIBS 19:240–244
Author information
Authors and Affiliations
Additional information
Correspondence to: G.J. King
Rights and permissions
About this article
Cite this article
King, G.J., Lynn, J.R. Constraints on mutability in a multiallelic gene family. J Mol Evol 41, 732–740 (1995). https://doi.org/10.1007/BF00173153
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00173153