Journal of Molecular Evolution

, Volume 24, Issue 3, pp 272–279 | Cite as

Recruitment of lysozyme as a major enzyme in the mouse gut: Duplication, divergence, and regulatory evolution

  • Michael F. Hammer
  • James W. Schilling
  • Ellen M. Prager
  • Allan C. Wilson


Two major types of lysozymec (M and P) occur in the mouse genus,Mus, and have been purified from an inbred laboratory strain (C58/J) ofM. domesticus. They differ in physical, catalytic, and antigenic properties as well as by amino acid replacements at 6 of 49 positions in the amino-terminal sequence. Comparisons with four other mammalian lysozymesc of known sequence suggest that M and P are related by a gene duplication that took place before the divergence of the rat and mouse lineages. M lysozyme is present in most tissues; achieves its highest concentration in the kidney, lung, and spleen; and corresponds to the lysozyme partially sequenced before from another strain ofM. domesticus. InM. domesticus and several related species, P lysozyme was detected chiefly in the small intestine, where it is probably produced mainly by Paneth cells. A survey of M and P levels in 22 species of muroid rodents (fromMus and six other genera) of known phylogenetic relationships suggests that a mutation that derepressed the P enzyme arose about 4 million years ago in the ancestor of the housemouse group of species. Additional regulatory shifts affecting M and P levels have taken place along lineages leading to other muroid species. Our survey of 187 individuals of wild house mice and their closest allies reveals a correlation between latitude of origin and level of intestinal lysozyme.

Key words

Enzymatic properties Primary sequence 22 Rodent species Tissue distribution Latitudinal variation 


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  1. Barnard EA (1969) Biological function of pancreatic ribonuclease. Nature 221:340–344PubMedGoogle Scholar
  2. Cámara VM, Prieur DJ (1984) Secretion of colonic isozyme of lysozyme in association with cecotrophy of rabbits. Am J Physiol 247:G19-G23PubMedGoogle Scholar
  3. Dobson DE, Prager EM, Wilson AC (1984) Stomach lysozymes of ruminants. I. Distribution and catalytic properties. J Biol Chem 259:11607–11616PubMedGoogle Scholar
  4. Eigelsbach HT, McGann VG (1981) The genusFrancisella. In: Starr MP, Stolp H, Trüper HG, Balows A, Schlegel HG (eds) The prokaryotes, vol 1. Springer-Verlag, Berlin, pp 1086–1090Google Scholar
  5. Ferris SD, Sage RD, Prager EM, Ritte U, Wilson AC (1983) Mitochondrial DNA evolution in mice. Genetics 105:681–721PubMedGoogle Scholar
  6. Hammer MF (1984) Of mice and lysozyme: evolution and regulatory genetics. PhD thesis, University of California, BerkeleyGoogle Scholar
  7. Hammer MF, Wilson AC (1987) Regulatory and structural genes for lysozymes of mice. Genetics 115: in pressGoogle Scholar
  8. Hammer MF, Erlandsen S, Prager EM, Wilson AC (1984) Evolution and regulatory genetics of lysozymes in mice [Abstract]. Fed Proc 43:1795Google Scholar
  9. Hunkapiller MW, Hood LE (1983) Analysis of phenylthiohydantoins by ultrasensitive gradient high-performance liquid chromatography. Methods Enzymol 91:486–493PubMedGoogle Scholar
  10. Jacobs LL (1978) Fossil rodents (Rhizomyidae and Muridae) from neogene Siwalik deposits, Pakistan. Museum Northern Ariz Bull 52:1–103Google Scholar
  11. Jaeger J-J, Tong H, Denys C (1986) The age of theMus-Rattus divergence: paleontological data compared with the molecular clock. C R Acad Sci Paris [II] 302:917–922Google Scholar
  12. Jollès P, Jollès J (1984) What's new in lysozyme research? Mol Cell Biochem 63:165–189PubMedGoogle Scholar
  13. Jollès P, Schoentgen F, Jollès J, Dobson DE, Prager EM, Wilson AC (1984) Stomach lysozymes of ruminants. II. Amino acid sequence of cow lysozyme 2 and immunological comparisons with other lysozymes. J Biol Chem 259:11617–11625PubMedGoogle Scholar
  14. Kapperud G (1975)Yersinia enterocolitica in small rodents from Norway, Sweden and Finland. Acta Pathol Microbiol Scand [B] 83:335–342Google Scholar
  15. Klockars M, Reitamo S (1975) Tissue distribution of lysozyme in man. J Histochem Cytochem 23:932–940PubMedGoogle Scholar
  16. Klockars M, Adinolfi MC, Osserman EF (1974) Ontogeny of lysozyme in the rat. Proc Soc Exp Biol Med 145:604–609PubMedGoogle Scholar
  17. Landry SO Jr (1970) The Rodentia as omnivores. Q Rev Biol 45:351–372PubMedGoogle Scholar
  18. Lawson AJ, Smit RA, Jeffers NA, Osborne JW (1982) Isolation of rat intestinal crypt cells. Cell Tissue Kinet 15:69–80PubMedGoogle Scholar
  19. Marshall JT (1986) Systematics of the genusMus. Curr Top Microbiol Immunol 127:12–18PubMedGoogle Scholar
  20. Martin SL, Voliva CF, Hardies SC, Edgell MH, Hutchison CA III (1985) Tempo and mode of concerted evolution in the L1 repeat family of mice. Mol Biol Evol 2:127–140PubMedGoogle Scholar
  21. McBee RH (1977) Fermentation in the hindgut. In: Clarke RTJ, Bauchop T (eds) Microbial ecology of the gut. Academic Press, London, pp 185–222Google Scholar
  22. McHenery JG, Birkbeck TH, Allen JA (1979) The occurrence of lysozyme in marine bivalves. Comp Biochem Physiol [B] 63:25–28Google Scholar
  23. Montero C, Erlandsen SL (1978) Immunocytochemical and histochemical studies on intestinal epithelial cells producing both lysozyme and mucosubstance. Anat Rec 190:127–142PubMedGoogle Scholar
  24. Osserman EF, Canfield RE, Beychok S (eds) (1974) Lysozyme. Academic Press, New YorkGoogle Scholar
  25. Parry RM Jr, Chandan RC, Shahani KM (1965) A rapid and sensitive assay of muramidase. Proc Soc Exp Biol Med 119: 384–386PubMedGoogle Scholar
  26. Peeters TL, Vantrappen GR (1976) Purification and partial characterization of lysozyme from mouse small intestine. Experientia 32:1125–1126PubMedGoogle Scholar
  27. Riblet RJ (1974) Sequence studies of mouse lysozyme. In: Osserman EF, Canfield RE, Beychok S (eds) Lysozyme. Academic Press, New York, pp 89–93Google Scholar
  28. Sage RD (1981) Wild mice. In: Foster HL, Small JD, Fox JG (eds) The mouse in biomedical research, vol 1. Academic Press, New York, pp 39–90Google Scholar
  29. Sarich VM (1985) Rodent macromolecular systematics. In: Luckett WP, Hartenberger J-L (eds) Evolutionary relationships among rodents: a multidisciplinary analysis. Plenum Press, New York, pp 423–452Google Scholar
  30. Savage DE, Russell DE (1983) Mammalian paleofaunas of the world. Addison-Wesley, Reading, MassachusettsGoogle Scholar
  31. Speece AJ (1964) Histochemical distribution of lysozyme activity in organs of normal mice and radiation chimeras. J Histochem Cytochem 12:384–391PubMedGoogle Scholar
  32. Stewart C-BR (1986) Lysozyme evolution in Old World monkeys. PhD thesis, University of California, BerkeleyGoogle Scholar
  33. Weiser MM (1973) Intestinal epithelial cell surface membrane glycoprotein synthesis. I. An indicator of cellular differentiation. J Biol Chem 248:2536–2541PubMedGoogle Scholar
  34. White TJ (1976) Protein evolution in rodents. PhD thesis, University of California, BerkeleyGoogle Scholar
  35. White TJ, Mross GA, Osserman EF, Wilson AC (1977) Primary structure of rat lysozyme. Biochemistry 16:1430–1436PubMedGoogle Scholar
  36. Wilson AC, Carlson SS, White TJ (1977) Biochemical evolution. Annu Rev Biochem 46:573–639PubMedGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1987

Authors and Affiliations

  • Michael F. Hammer
    • 1
  • James W. Schilling
    • 2
  • Ellen M. Prager
    • 1
  • Allan C. Wilson
    • 1
  1. 1.Department of BiochemistryUniversity of CaliforniaBerkeleyUSA
  2. 2.California BiotechnologyMountain ViewUSA

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