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. 1997 Dec;147(4):1863–1872. doi: 10.1093/genetics/147.4.1863

Nucleotide Sequence Evolution at the κ-Casein Locus: Evidence for Positive Selection within the Family Bovidae

T J Ward 1, R L Honeycutt 1, J N Derr 1
PMCID: PMC1208352  PMID: 9409842

Abstract

κ-Casein is a mammalian milk protein involved in a number of important physiological processes. In the gut, the ingested protein is split into an insoluble peptide (para κ-casein) and a soluble hydrophilic glycopeptide (caseinomacropeptide). Caseinomacropeptide is responsible for increased efficiency of digestion, prevention of neonate hypersensitivity to ingested proteins, and inhibition of gastric pathogens. Variation within this peptide has significant effects associated with important traits such as milk production. The nucleotide sequences for regions of κ-casein exon and intron four were determined for representatives of the artiodactyl family Bovidae. The pattern of nucleotide substitution in κ-casein sequences for distantly related bovid taxa demonstrates that positive selection has accelerated their divergence at the amino acid sequence level. This selection has differentially influenced the molecular evolution of the two κ-casein split peptides and is focused within a 34-codon region of caseinomacropeptide.

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Selected References

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  1. Alexander L. J., Stewart A. F., Mackinlay A. G., Kapelinskaya T. V., Tkach T. M., Gorodetsky S. I. Isolation and characterization of the bovine kappa-casein gene. Eur J Biochem. 1988 Dec 15;178(2):395–401. doi: 10.1111/j.1432-1033.1988.tb14463.x. [DOI] [PubMed] [Google Scholar]
  2. Allard M. W., Miyamoto M. M., Jarecki L., Kraus F., Tennant M. R. DNA systematics and evolution of the artiodactyl family Bovidae. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3972–3976. doi: 10.1073/pnas.89.9.3972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dev B. C., Sood S. M., DeWind S., Slattery C. W. Kappa-casein and beta-caseins in human milk micelles: structural studies. Arch Biochem Biophys. 1994 Nov 1;314(2):329–336. doi: 10.1006/abbi.1994.1450. [DOI] [PubMed] [Google Scholar]
  4. Gatesy J., Hayashi C., Cronin M. A., Arctander P. Evidence from milk casein genes that cetaceans are close relatives of hippopotamid artiodactyls. Mol Biol Evol. 1996 Sep;13(7):954–963. doi: 10.1093/oxfordjournals.molbev.a025663. [DOI] [PubMed] [Google Scholar]
  5. Grassly N. C., Holmes E. C. A likelihood method for the detection of selection and recombination using nucleotide sequences. Mol Biol Evol. 1997 Mar;14(3):239–247. doi: 10.1093/oxfordjournals.molbev.a025760. [DOI] [PubMed] [Google Scholar]
  6. Gutiérrez-Adán A., Maga E. A., Meade H., Shoemaker C. F., Medrano J. F., Anderson G. B., Murray J. D. Alterations of the physical characteristics of milk from transgenic mice producing bovine kappa-casein. J Dairy Sci. 1996 May;79(5):791–799. doi: 10.3168/jds.S0022-0302(96)76427-5. [DOI] [PubMed] [Google Scholar]
  7. Hastings K. E., Emerson C. P., Jr Codon usage in muscle genes and liver genes. J Mol Evol. 1983;19(3-4):214–218. doi: 10.1007/BF02099968. [DOI] [PubMed] [Google Scholar]
  8. Higgins D. G., Sharp P. M. Fast and sensitive multiple sequence alignments on a microcomputer. Comput Appl Biosci. 1989 Apr;5(2):151–153. doi: 10.1093/bioinformatics/5.2.151. [DOI] [PubMed] [Google Scholar]
  9. Hughes A. L., Nei M. Nucleotide substitution at major histocompatibility complex class II loci: evidence for overdominant selection. Proc Natl Acad Sci U S A. 1989 Feb;86(3):958–962. doi: 10.1073/pnas.86.3.958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hughes A. L., Nei M. Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature. 1988 Sep 8;335(6186):167–170. doi: 10.1038/335167a0. [DOI] [PubMed] [Google Scholar]
  11. Hughes A. L. Positive selection and interallelic recombination at the merozoite surface antigen-1 (MSA-1) locus of Plasmodium falciparum. Mol Biol Evol. 1992 May;9(3):381–393. doi: 10.1093/oxfordjournals.molbev.a040730. [DOI] [PubMed] [Google Scholar]
  12. Janecek L. L., Honeycutt R. L., Adkins R. M., Davis S. K. Mitochondrial gene sequences and the molecular systematics of the artiodactyl subfamily bovinae. Mol Phylogenet Evol. 1996 Aug;6(1):107–119. doi: 10.1006/mpev.1996.0063. [DOI] [PubMed] [Google Scholar]
  13. Jukes T. H., King J. L. Evolutionary nucleotide replacements in DNA. Nature. 1979 Oct 18;281(5732):605–606. doi: 10.1038/281605a0. [DOI] [PubMed] [Google Scholar]
  14. Lee Y. H., Ota T., Vacquier V. D. Positive selection is a general phenomenon in the evolution of abalone sperm lysin. Mol Biol Evol. 1995 Mar;12(2):231–238. doi: 10.1093/oxfordjournals.molbev.a040200. [DOI] [PubMed] [Google Scholar]
  15. Mercier J. C., Chobert J. M., Addeo F. Comparative study of the amino acid sequences of the caseinomacropeptides from seven species. FEBS Lett. 1976 Dec 31;72(2):208–214. doi: 10.1016/0014-5793(76)80972-6. [DOI] [PubMed] [Google Scholar]
  16. Metz E. C., Palumbi S. R. Positive selection and sequence rearrangements generate extensive polymorphism in the gamete recognition protein bindin. Mol Biol Evol. 1996 Feb;13(2):397–406. doi: 10.1093/oxfordjournals.molbev.a025598. [DOI] [PubMed] [Google Scholar]
  17. Miyata T., Yasunaga T., Nishida T. Nucleotide sequence divergence and functional constraint in mRNA evolution. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7328–7332. doi: 10.1073/pnas.77.12.7328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Modi W. S., Gallagher D. S., Womack J. E. Evolutionary histories of highly repeated DNA families among the Artiodactyla (Mammalia). J Mol Evol. 1996 Mar;42(3):337–349. doi: 10.1007/BF02337544. [DOI] [PubMed] [Google Scholar]
  19. Nei M., Gojobori T. Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol. 1986 Sep;3(5):418–426. doi: 10.1093/oxfordjournals.molbev.a040410. [DOI] [PubMed] [Google Scholar]
  20. Nei M., Jin L. Variances of the average numbers of nucleotide substitutions within and between populations. Mol Biol Evol. 1989 May;6(3):290–300. doi: 10.1093/oxfordjournals.molbev.a040547. [DOI] [PubMed] [Google Scholar]
  21. Pinder S. J., Perry B. N., Skidmore C. J., Savva D. Analysis of polymorphism in the bovine casein genes by use of the polymerase chain reaction. Anim Genet. 1991;22(1):11–20. doi: 10.1111/j.1365-2052.1991.tb00642.x. [DOI] [PubMed] [Google Scholar]
  22. Qian Z. Y., Jollès P., Migliore-Samour D., Schoentgen F., Fiat A. M. Sheep kappa-casein peptides inhibit platelet aggregation. Biochim Biophys Acta. 1995 Jun 9;1244(2-3):411–417. doi: 10.1016/0304-4165(95)00047-f. [DOI] [PubMed] [Google Scholar]
  23. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  24. Shields D. C., Sharp P. M., Higgins D. G., Wright F. "Silent" sites in Drosophila genes are not neutral: evidence of selection among synonymous codons. Mol Biol Evol. 1988 Nov;5(6):704–716. doi: 10.1093/oxfordjournals.molbev.a040525. [DOI] [PubMed] [Google Scholar]
  25. Smith J. M., Haigh J. The hitch-hiking effect of a favourable gene. Genet Res. 1974 Feb;23(1):23–35. [PubMed] [Google Scholar]
  26. Swanson W. J., Vacquier V. D. Extraordinary divergence and positive Darwinian selection in a fusagenic protein coating the acrosomal process of abalone spermatozoa. Proc Natl Acad Sci U S A. 1995 May 23;92(11):4957–4961. doi: 10.1073/pnas.92.11.4957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ticher A., Graur D. Nucleic acid composition, codon usage, and the rate of synonymous substitution in protein-coding genes. J Mol Evol. 1989 Apr;28(4):286–298. doi: 10.1007/BF02103424. [DOI] [PubMed] [Google Scholar]
  28. Wells D., Bains W., Kedes L. Codon usage in histone gene families of higher eukaryotes reflects functional rather than phylogenetic relationships. J Mol Evol. 1986;23(3):224–241. doi: 10.1007/BF02115579. [DOI] [PubMed] [Google Scholar]

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