Genetic drift

"...the constant tendency of genes to evolve even in the absence of selective forces. Genetic drift is fueled by spontaneous neutral mutations that disappear or become fixed in a population at random. Inbred lines separated from a common ancestral pair can drift rapidly apart from each other." (Silver, 1995).

Causes of genetic drift

Genetic drift happens slowly, subtly, and is difficult to detect and control. It is caused by a number of factors, including:

  • residual heterozygosity in or incomplete breeding of a colony before it is separated from progenitors,
  • undetected spontaneous mutations that become fixed in a colony, and
  • separation of a subcolony from its parent colony for more than 20 generations.

Examples of genetic drift

substrains of the C57BL strain
At least 40 C57BL substrains develop between 1930 and 1970, some of which are due to genetic drift (adapted from Bailey 1977 by Dr. Michael V. Wiles, The Jackson Laboratory)
  • At least 40 C57BL substrains develop between 1930 and 1970 (see chart): most are probably due to maintaining subcolonies separate from the orginating colony for more than 10 generations; some are due to deliberate outcrossing; some are due to genetic drift.
  • Immunological variants are discovered among A, AKR, BALB/c, CBA, C3H, C57BL, C57L, DBA, WG strains (Bailey, 1982).
  • Substrains C57BL/6N, C57BL/6JNmg, and C57BL/6JKun are phenotypically different from each other and from the C57BL/6J founder line (Radulovic et al. 1998, Sluyter et al. 1999; Stiedl et al. 1999; Roth et al. 2002; Wotjak 2003).
  • C57BL/6JOlaHsd, a substrain of C57BL, has a spontaneous deletion in part of the alpha-synuclein gene (Specht et al. 2001; Wotjak 2003).
  • A deletion of the Klrd1 gene on Chr 6 becomes fixed in JAX® Mice strain DBA/2J. Klrd1 encodes the CD94 protein, which is thought to play a role in self tolerance and the ability of NK cells to distinguish between MHC Ilow and MHC Ihigh target cells (Vance et al. 2002; Wilhelm et al. 2003).
  • A spontaneous deletion of two ion channel genes, Kcnq2 and Chrna4, in a C57BL/6J strain generates a mouse model of epilepsy (Yang et al. 2003).
  • The expression of a hippocampus specific protein differs between C57BL/6JNmg and C57BL/6JKun (Sluyter et al. 1999).
  • C3H/HeJ mice are homozygous for a paracentric inversion in Chromosome 6 (JAX NotesTM 2003).

Do your part to lessen the impact of genetic drift

You can lessen the impact of genetic drift on mouse-based biomedical research by practicing the following:

  • Obtain mice from a reliable breeding source.
  • Instead of maintaining your own private colonies of these mice, periodically obtain new breeding stock from that source. Although colonies of inbred mice expanded from our breeding stock can be maintained either by sib or non-sib matings, they may develop into substrains if they are expanded either beyond three generations (if maintained by non-sib matings) or ten generations (if maintained by sib matings).
  • Avoid comparing results from substrains that either arose early in a strain's inbreeding regimen or that have been long separated.
  • Use proper nomenclature: accurately describe mouse models, including inbreds, hybrids, transgenics, spontaneous mutants, congenics, wild-derived inbreds, recombinant congenics, and strains with chromosome aberrations; designate genetic background, relation to other strains, transgenes (including the species of origin), alleles, mode of inheritance, and laboratory of origin. For more detailed information on mouse strain nomenclature, consult the following:
  • In all your communications, cite 1) the facility that maintains the breeding colony of the mouse model you used and 2) the source of and the date you obtained your breeding stock. Remember, if you obtain breeding stock either from The Jackson Laboratory or our approved propogators, our "Conditions of Use" policy applies.

Learn more about The Jackson Laboratory's unique Genetic Stability Program, which limits genetic drift.

A bibliography is available for sources referenced on this page.