Aa

+a

p2 + fpq

ap2 + afpq

Aa

d

2pq - f2pq

d2pq - df2pq

aa

-a

q2 + fpq

-aq2 - afpq

Population mean: ap2 + d2pq - df2pq - aq2 = a(p - q) + d2pq(1 - f)

Population mean: ap2 + d2pq - df2pq - aq2 = a(p - q) + d2pq(1 - f)

and is associated with a decline in the average phenotype in a population, a phenomenon referred to as inbreeding depression. Since the early twentieth century, studies in animals and plants that have been intentionally inbred provide ample evidence that decreased performance, growth, reproduction, viability (all measures of fitness), and abnormal phenotypes are associated with consanguineous mating. A related phenomenon is heterosis or hybrid vigor, characterized by beneficial consequences of increased heterozygosity such as increased viability and reproduction, or the reverse of inbreeding depression. One example is the heterosis exhibited in corn, which has lead to the nearly universal use of F1 hybrid seed for agriculture in developed countries.

There is evidence that humans experience inbreeding depression, based on observed phenotypes in the offspring of couples with known consanguinity. For example, mortality among children of first-cousin marriages was 4.5% greater than for marriages between unrelated individuals measured in a range of human populations (see review by Jorde 1997). Human studies have utilized existing parental pairs with relatively low levels of inbreeding, such as uncle/ niece, first cousins, or second cousins, in contrast to animal and plant studies where both very high levels and a broad range of inbreeding coefficients are achieved intentionally. Drawing conclusions about the causes of variation in phenotypes from such observational studies requires extreme caution, since the prevalence of consanguineous mating in humans is also correlated with social and economic variables such as illiteracy, age at marriage, duration of marriage, and income. These latter variables are therefore not independent of consanguinity and can themselves contribute to variation in pheno-types such as fertility and infant mortality (see Bittles et al. 1991, 2002).

The Mendelian genetic causes of inbreeding depression have been a topic of population genetics research for more than a century. There are two classical hypotheses to explain inbreeding depression and changes in fitness as the inbreeding coefficient increases (Charlesworth & Charlesworth 1999; Carr & Dudash 2003). Both hypotheses predict that levels of inbreeding depression will increase along with consanguineous mating that increases homozygosity, although for different reasons (Table 2.11). The first hypothesis, often called the dominance hypothesis, is that increasing homozygosity increases the pheno-typic expression of fully and partly recessive alleles with deleterious effects. The second hypothesis is that inbreeding depression is the result of the decrease in the frequency of heterozygotes that occurs with consanguineous mating. This explanation supposes that heterozygotes have higher fitness than homozygotes (heterosis) and is called the overdominance hypothesis. In addition, the fitness interactions of alleles at different loci (epistasis; see Chapter 9) may also cause inbreeding depression, a hypothesis that is particularly difficult to test (see Carr & Dudash 2003). These causes of inbreeding depression may all operate simultaneously.

These dominance and overdominance hypotheses make different testable predictions about

Heterosis The increase in performance, survival, and ability to reproduce of individuals possessing heterozygous loci (hybrid vigor); increase in the population average phenotype associated with increased heterozygosity. Inbreeding depression The reduction in performance, survival, and ability to reproduce of individuals possessing homozygous loci; decrease in population average phenotype associated with consanguineous mating that increases homozygosity.

Table 2.11 A summary of the Mendelian basis of inbreeding depression under the dominance and overdominance hypotheses along with predicted patterns of inbreeding depression with continued consanguineous mating.

Hypothesis

Mendelian basis

Low-fitness genotypes

Changes in inbreeding depression with continued consanguineous mating

Dominance Overdominance

Recessive and partly recessive deleterious alleles

Heterozygote advantage or heterosis

Only homozygotes for deleterious recessive alleles

All homozygotes

Purging of deleterious alleles that is increasingly effective as degree of recessiveness increases

No changes as long as consanguineous mating keeps heterozygosity low

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