Dear Steven, I think different topics might be slightly muddled in this question: 1) the heterozygote advantage in cases where the effect of a single gene on the phenotype is well known and has strong phenotypic effects, with 2) heterozygosity advantage as one of the mechanisms underlying inbreeding depression. The first case you mention, is not central to the final question you pose. In the second case, molecular ecologists tend to use heterozygosity measured in neutral markers to infer inbreeding levels in natural populations, or to reveal the strength of the associations between heterozygosity and fitness-related traits. Most often this refers to complex traits (affected by many genes) normally distributed and hence that are amenable of study using quantitative genetics techniques. Thus, when looking at empirical studies it is important to find-out what genes (coding, non-coding), the strength of their effects, the number of genes/markers and what type of trait (simple or complex) the researchers are dealing with.

First, sickle cell anemia is an example of heterozygote advantage, one of the mechanisms that allow the maintenance of genetic polymorphism through balancing selection. The other well-known mechanism is frequency-dependent selection (as in the peppered moth phenotypic change to melanic forms during the industrial revolution). Thus the heterozygote advantage of the sickle-cell gene is context-dependent and depends on the frequency of the protozoan parasite in the population; outside malaria infested areas there is no such heterozygote advantage. So for answering your first question “how common — across the genome and across taxa is heterozygote superiority?” you would have to first account as well for the context-dependency and reformulate your question as follows: “how common — across the genome, taxa, and environmental contexts (phenotype by environment interactions) is heterozygote superiority?”. But there is more to this, because the answer won't be the same for complex traits (dozens of genes) and simple traits (1 gene).

Second, and importantly, regarding your second point: inbreeding depression does exclusively imply a homozygote disadvantage; there are other potential mechanisms such as overdominance (with neutral markers you can also have associative overdominance). Inbreeding depression is just the reduction in fitness that happens with the increase in frequency of mating between related individuals (recognized by Darwin in 1868 and formally defined by Morton 1956). Roff’s 2002 empirical study supported the partial dominance hypothesis, which had been previously highlighted as the main underlying mechanism by the Charlesworth’s. It overall seems that the overdominance hypothesis has received significantly less support than the others (recessives, or mild recessives). 

I am unsure of at what level you want to explore this question further. If you want to dive more in the theory of quantitative genetics behind it go for the Charlesworth work, recent chapters by Bruce Walsh ( I think they are available online), Patrice David... If you are interested on heterozygosity-fitness correlations in wild populations (using neutral markers) you should start looking at Chapman 2011 (recent review in Mol Ecol), work from Amos, Aparicio, Balloux, Coltman, Coulson, Hansson, Keller, Ortego, Pemberton, Slate, etc… (these authors have also worked on the power of different heterozygosity-based measures). For papers showing heterozygosity on coding loci or allozymes on fitness traits such as growth or metabolic efficiency you should look at 70s-80s work on invertebrates. Mitton and Grant 1984 gives a good overview. Hope this helps.

Steven, I agree to D. Roff that inbreeding depression results more from an increased incidence of harmful recessives, but heterozygote superiority has little relation to this effect. Hybrid's superiority (in plants) can be explained (besides many other theories) by wider functional adaptation range of organism with two different alleles for one loci.

There is negative positive genetics, if heterozygotes are developed for flowering plants, they will provide high yield, may show high vigour with pest resistance to disease tolerant, but on negative sides if heterozygosity increases in case of plants, it will increase infection rate, host invasion, lethality and drug resistance, even these heterozygotes show high survival rate and eco-climatically adapted. 

There is a negative and positive genetics, if heterozyosity increases in case of animals, then it will show increase in vigor, yield and tolerability against infection and diseases, climatic changes. if it occurs in microbes it will show drug resistance, high infection rate, lethality, host challange, and pathogenicity. 

I see frequent examples, particularly where auto- immune issues are discussed. See below.

Cutting Edge: Heterozygote Advantage in Autoimmune Disease: Hierarchy of Protection/Susceptibility Conferred by HLA and Killer Ig-Like Receptor Combinations in Psoriatic Arthritis1

 http://www.jimmunol.org/content/173/7/4273.long

However, see Phil Hedrick:

Virgin birth, genetic variation and inbreeding

Philip W Hedrick, Biol. Lett. 2007 3, published 22 December 2007

http://rsbl.royalsocietypublishing.org/content/3/6/715.full.pdf+html

Also see book:

Clonality: The Genetics, Ecology, and Evolution of Sexual Abstinence in Vertebrate Animals

John Avise

What about "hybrid vigour" concept ?

It depends on the species and the type of homozygous genes, if they are lethal they do the effect and enhance the chance of  heterozygote superiority.

In addition natural selection plays an important role in heterozygote superiority, i.e environment has an important role in the lethality of homozygotes.

Dear Steven, I think different topics might be slightly muddled in this question: 1) the heterozygote advantage in cases where the effect of a single gene on the phenotype is well known and has strong phenotypic effects, with 2) heterozygosity advantage as one of the mechanisms underlying inbreeding depression. The first case you mention, is not central to the final question you pose. In the second case, molecular ecologists tend to use heterozygosity measured in neutral markers to infer inbreeding levels in natural populations, or to reveal the strength of the associations between heterozygosity and fitness-related traits. Most often this refers to complex traits (affected by many genes) normally distributed and hence that are amenable of study using quantitative genetics techniques. Thus, when looking at empirical studies it is important to find-out what genes (coding, non-coding), the strength of their effects, the number of genes/markers and what type of trait (simple or complex) the researchers are dealing with.

First, sickle cell anemia is an example of heterozygote advantage, one of the mechanisms that allow the maintenance of genetic polymorphism through balancing selection. The other well-known mechanism is frequency-dependent selection (as in the peppered moth phenotypic change to melanic forms during the industrial revolution). Thus the heterozygote advantage of the sickle-cell gene is context-dependent and depends on the frequency of the protozoan parasite in the population; outside malaria infested areas there is no such heterozygote advantage. So for answering your first question “how common — across the genome and across taxa is heterozygote superiority?” you would have to first account as well for the context-dependency and reformulate your question as follows: “how common — across the genome, taxa, and environmental contexts (phenotype by environment interactions) is heterozygote superiority?”. But there is more to this, because the answer won't be the same for complex traits (dozens of genes) and simple traits (1 gene).

Second, and importantly, regarding your second point: inbreeding depression does exclusively imply a homozygote disadvantage; there are other potential mechanisms such as overdominance (with neutral markers you can also have associative overdominance). Inbreeding depression is just the reduction in fitness that happens with the increase in frequency of mating between related individuals (recognized by Darwin in 1868 and formally defined by Morton 1956). Roff’s 2002 empirical study supported the partial dominance hypothesis, which had been previously highlighted as the main underlying mechanism by the Charlesworth’s. It overall seems that the overdominance hypothesis has received significantly less support than the others (recessives, or mild recessives). 

I am unsure of at what level you want to explore this question further. If you want to dive more in the theory of quantitative genetics behind it go for the Charlesworth work, recent chapters by Bruce Walsh ( I think they are available online), Patrice David... If you are interested on heterozygosity-fitness correlations in wild populations (using neutral markers) you should start looking at Chapman 2011 (recent review in Mol Ecol), work from Amos, Aparicio, Balloux, Coltman, Coulson, Hansson, Keller, Ortego, Pemberton, Slate, etc… (these authors have also worked on the power of different heterozygosity-based measures). For papers showing heterozygosity on coding loci or allozymes on fitness traits such as growth or metabolic efficiency you should look at 70s-80s work on invertebrates. Mitton and Grant 1984 gives a good overview. Hope this helps.

Thanks Aurelio, this is comprehensive. 

Heterozygote superiority is rare (see Hedrick 2012 Trends Ecol Evol 27(12): 698-704), and many examples that are assumed to be heterozygote superiority, such as MHC loci, can be explained by heterozygote advantage through dominance (Penn et al. 2002 PNAS 99(17): 11260-11264; and more details in Penn 2002 Ethology, 108: 1-21). The distinction between heterozygote superiority (overdominance) versus heterozygote advantage (which can be due to overdominance or dominance) is important, but widely overlooked. Only overdominance is expected to drive genetic polymorphisms, though even this mechanism can maintain only low levels of diversity.

There are some loci which are always heterozygous and the classical example of this is the balanced lethal system.