Inbreeding and Inbreeding Depression

by

Donald M. Waller, Lukas F. Keller

• LAST REVIEWED: 30 August 2022
• LAST MODIFIED: 26 February 2020
• DOI: 10.1093/obo/9780199941728-0124

Introduction

Inbreeding (also referred to as “consanguinity”) occurs when mates are related to each other due to incest, assortative mating, small population size, or population sub-structuring. Inbreeding results in an excess of homozygotes and hence a deficiency of heterozygotes. This, in turn, exposes recessive genetic variation otherwise hidden by heterozygosity with dominant alleles relative to random mating. Interest in inbreeding arose from its use in animal and plant breeding programs to expose such variation and to fix variants in genetically homogenous lines. Starting with Gregor Mendel’s experiments with peas, geneticists have widely exploited inbreeding as a research tool, leading R. C. Lewontin to conclude that “Every discovery in classical and population genetics has depended on some sort of inbreeding experiment” (see Lewontin’s 1965 article “The Theory of Inbreeding.” Science 150:1800–1801). Charles Darwin wrote an entire book on the effects of inbreeding as measured in fifty-two taxa of plants. He and others noted that most plants and animals go to great length to avoid inbreeding, suggesting that inbreeding has high costs that often outweigh the benefits of inbreeding. Benefits of inbreeding include increased genetic transmission while the costs of inbreeding manifest as inbreeding depression when deleterious, mostly recessive alleles otherwise hidden as heterozygotes emerge in homozygote form upon inbreeding. Inbreeding also reduces fitness when heterozygotes are more fit than both homozygotes, but such overdominance is rare. Recurrent mutation continuously generates deleterious recessive alleles that create a genetic “load” of deleterious mutations mostly hidden within heterozygotes in outcrossing populations. Upon inbreeding, the load is expressed when deleterious alleles segregate as homozygotes, causing often substantial inbreeding depression. Although inbreeding alone does not change allele frequencies, it does redistribute genetic variation, reducing it within families or populations while increasing it among families or populations. Inbreeding also increases selection by exposing deleterious recessive mutations, a process called purging that can deplete genetic variation. For all these reasons, inbreeding is a central concept in evolutionary biology. Inbreeding is also central to conservation biology as small and isolated populations become prone to inbreeding and thus suffer inbreeding depression. Inbreeding can reduce population viability and increase extinction risk by reducing individual survival and/or reproduction. Such effects can often be reversed, however, by introducing new genetic material that re-establishes heterozygosity (“genetic rescue”). The current availability of DNA sequence and expression data is now allowing more detailed analyses of the causes and evolutionary consequences of inbreeding.

General Overviews

Classical population genetics has long concerned itself with the systems of mating and population structures that generate inbreeding and inbreeding depression, the decline in fitness due to inbreeding (see Early-20th-Century History of Inbreeding Research and Textbooks). Population geneticists exploring the forces that generate and maintain genetic variation analyze how the steady flow of deleterious mutations is countered by selection resulting in an equilibrium genetic load (mutation-selection balance). Recessive deleterious alleles are exposed as homozygotes upon inbreeding, expressing the load as inbreeding depression. Charlesworth and Charlesworth 1987, Crow 1993, and Charlesworth and Charlesworth 1999 provide authoritative reviews of the origin and dynamics of the inbreeding load. Charlesworth and Willis 2009 emphasizes the standing genetic variation in fitness that exists in most populations and summarizes evidence that most inbreeding depression reflects the segregation of dominant rather than overdominant alleles. The evolutionary dynamics of these load loci can be complex and depends on many factors including levels of dominance, fitness effects, how these vary over environments, epistatic interactions among loci, gene flow, and the associations that arise among loci. The authors mentioned above, Keller and Waller 2002, and Hedrick and Garcia-Dorado 2016 all emphasize how these complex effects make it difficult to predict dynamics of the inbreeding load. The volume edited by Thornhill 1993 (see Textbooks) presents a diversity of perspectives on inbreeding in a wide range of organisms with authors ranging from theoreticians to experts in particular groups, including the creative evolutionist W. D. Hamilton. Inbreeding is both a tool and a hazard in plant and animal breeding, leading Kristensen and Sørensen 2005 to review the theory and empirical results on inbreeding effects so they can recommend how to minimize its risks in breeding programs. Inbreeding depression is also a major concern in conservation biology, a topic reviewed by Hedrick and Kalinowski 2000. New methods and the ready availability of DNA sequence data in recent years (see Methods to Measure Inbreeding) are now providing more detailed pictures of inbreeding and its evolutionary consequences in wild populations.

• Charlesworth, D., and B. Charlesworth. 1987. Inbreeding depression and its evolutionary consequences. Annual Review of Ecology and Systematics 18:237–268.

  DOI: 10.1146/annurev.es.18.110187.001321

  Review of how the genetic load of mostly recessive deleterious mutations manifests as inbreeding depression and how these effects modify load dynamics and the evolution of other (e.g., reproductive) characteristics. Reviews support for the role of dominance rather than overdominance as the genetic basis for inbreeding effects.

• Charlesworth, B., and D. Charlesworth. 1999. The genetic basis of inbreeding depression. Genetical Research 74:329–340.

  DOI: 10.1017/S0016672399004152

  A clear review of the theory and empirical evidence for directional dominance as the primary mechanism causing inbreeding depression. They also describe the meager data available on the distribution of mutational effects and implications of these for how inbreeding depression evolves.

• Charlesworth, D., and J. H. Willis. 2009. The genetics of inbreeding depression. Nature Reviews Genetics 10:783–796.

  DOI: 10.1038/nrg2664

  A general review of the basis for inbreeding depression, drawing on both theory and recent empirical evidence. The article stresses the practical significance of inbreeding depression for understanding the dynamics of mating system evolution and methods and outcomes in plant and animal breeding.

• Crow, J. F. 1993. Mutation, mean fitness, and genetic load. Oxford Series in Evolutionary Biology 9:3–42.

  Authoritative historical review of the ideas and theory related to genetic load, including how recurrent mutations with various effect sizes and levels of dominance affect population fitness. Emphasizes how the architecture of the genetic load varies depending on population size and discusses evidence that dominance rather than overdominance tends to generate most of the inbreeding depression we observe.

• Hedrick, P. W., and S. T. Kalinowski. 2000. Inbreeding depression in conservation biology. Annual Review of Ecology and Systematics 31:139–162.

  DOI: 10.1146/annurev.ecolsys.31.1.139

  A review of the evidence for inbreeding depression, purging, and genetic rescue in the context of the management and the conservation of endangered species.

• Hedrick, P. W., and A. Garcia-Dorado. 2016. Understanding inbreeding depression, purging, and genetic rescue. Trends in Ecology & Evolution 31:940–952.

  DOI: 10.1016/j.tree.2016.09.005

  An age-of-genomics review of how mutation, gene flow, and selection interact to affect dynamics of the inbreeding load. Both selection on deleterious alleles (purging) and the introduction of beneficial alleles through gene flow at loci with a high frequency of deleterious alleles (genetic rescue) can act to reduce the inbreeding load and are therefore important for the survival of inbred populations. However, such benefits also involve risks that may limit their success.

• Keller, L. F., and D. M. Waller. 2002. Inbreeding effects in the wild. Trends in Ecology & Evolution 17:230–241.

  DOI: 10.1016/S0169-5347(02)02489-8

  A broad overview that reviews basic theory as well as growing empirical evidence for the significance of inbreeding effects under natural conditions. Highlights key studies confirming that effects of inbreeding and fixation can be rapidly reversed when organisms from small isolated populations are crossed with those from large populations (genetic rescue).

• Kristensen, T. N., and A. C. Sørensen. 2005. Inbreeding—lessons from animal breeding, evolutionary biology and conservation genetics. Animal Science 80:121–133.

  DOI: 10.1079/ASC41960121

  Animal breeders inbreed livestock to expose traits and select for economic traits. Kristensen and Sørensen review theory and empirical results on model organisms to conclude that inbreeding depresses both mean fitness and quantitative genetic variation. Because these effects could limit breeding success, the authors stress the importance of controlling inbreeding in livestock populations.