By Carol Beuchat PhD
I have two bucket lists. One for the things I want to experience and accomplish in life, which despite regular culling continues to exceed what I can reasonably expect to do in my time on this earth. The other bucket list is a list of topics related to genetics and breeding dogs that I want to write about. This list gets longer by the day, and I can only hope that at some point it will be so long that I can start tossing off the ones that are so far down the list that I have no hope of ever getting to. This might make the list look shorter, but it won't reduce the importance of addressing those topics.
The myth of hybrid vigor in dogs is a topic I've been putting off, hoping it would fall off the bottom of the list. But it keeps coming up, and the urgency of addressing it keeps smacking me in the face. So it's time.
Let me say first that this will be about the biology of genes. Genetics is complicated, and it's more important that I write something dog breeders will understand than mention all the little nuances that I wouldn't gloss over if I was writing for a scientific audience. The thing for you to understand is that there is a truth, supported by decades of data as well as a scientific explanation that is firmly rooted in our fundamental understandings about the way genetics works. So I'm sure some people will respond with "But..." and bring up something I didn't talk about that they hope will dismiss all of this as nonsense. There is much more we could talk about, but there are no "but"s that will change the simple facts, and don't let anybody try to convince you otherwise who is not prepared to haul out their documentation.
Over and over, I run into discussions about "hybrid vigor" and why (supposedly) it doesn't occur in dogs. The arguments usually center on some discussion about purebred and mixed breed dogs, and the position supported is that purebred dogs are just as healthy as mixed breed dogs. These ideas get very wide and enthusiastic support from dog breeders and even get extended as a reason why Doodles and other deliberate crosses are a disaster. Published studies are pointed to as supporting this, and even people with relevant professional expertise weigh in with support. But as I said before, there is a truth here that we really need to talk about.
Before we can address the hybrid vigor myth, we need to talk about inbreeding. This is going to on a bit, but inbreeding and hybrid vigor (which we're going to refer to with the scientific term "heterosis") are inextricably linked, and we can't adequatly explain heterosis without understanding some basic consequences of inbreeding. So bear with me.
Inbreeding is the mating of related animals. They can be closely related or distantly related, and we might want to distinguish between close inbreeding and "less close" linebreeding, but for genetics it's all inbreeding, and that's what we will call it here.
Related animals are likely to share alleles as a consequence of common ancestors, so mating related animals makes it more likely that offspring will inherit two copies of the same gene. We would refer to the alleles at that locus as homozygous (i.e., the same). If there are two different alleles at a locus, it is heterozygous. As a consequence of simple inheritance then, inbreeding increases homozygosity and reduces heterozygosity.
Animal breeders noticed long ago that although inbreeding had the advantages of improving the predictably and uniformity of offspring, there was also an effect that could be generally described as "loss of vigor" (Wright 1922; Lush 1943; and I discuss this here). These effects could be very subtle and even be overlooked as reflecting the normal variation in the quality of a group of animals, but research over the last 100 years has confirmed that this phenomenon is real (Charlesworth & Charlesworth 1987; Charles & Charlesworth 1999; Charlesworth & Willis 2009). We call it "inbreeding depression".
Inbreeding depression is not an increase in the incidence of genetic disorders of relatively high heritability like PRA or cardiomyopathy or hemolytic anemia. Rather it refers to loss of what biologists call "fitness", which encompasses the breadth of traits that affect an animal's ability to successfully pass its genes on to the next generation. Animals that die before reproducing have a fitness of zero. Animals that successfully reproduce but don't properly care for their offspring, which die as a consequence, also have a fitness of zero. Animals that have a high level of fitness produce offspring that go on to reproduce themselves and thereby perpetuate their genes in the population, and animals that do that less effectively or fail entirely have low or zero fitness.
In the context of breeding animals and plants, when we're talking about inbreeding depression we're usually referring to the collection of traits that affect reproduction and lifespan such as fertility, offspring size, pre- and post-natal mortality, maternal care, resistance to disease, and general "vigor and vitality". These effects have been documented in many thousands of studies and in all manner of organisms, and although there is much yet to be learned about it, there is no debate about the fact that it is a real phenomenon in both wild and domestic animals (Nicholas 1995).
Why do inbred animals have lower fitness? Because inbreeding results in an increase in genomic homozygosity, and homozygosity reduces fitness, resulting in inbreeding depression (Charlesworth & Charlesworth 2009). Homozygosity can reduce fitness because it increases the expression of deleterious recessive alleles, some of which are lethal and can result in death early in embryonic development. Likewise, there can be high levels of homozygosity in many alleles of small effect that control reproduction and other developmentally and physiologically complex processes. Homozygosity also reduces the beneficial effects of "overdominance", in which heterozygosity at a locus is advantageous over homozygosity of either allele ("heterozygote advantage") (Charlesworth & Willis 2009). (I have discussed some interesting examples of heterozygote advantage here.) We could say much more about the genetics of inbreeding depression, and there are some sources in the references at the end that address the details, but these are the basics of what we need to understand about inbreeding depression as it is going to relate to the issue of heterosis.
Of course, it is important to note that inbreeding depression occurs in dogs just as in any other mammal. As the level of inbreeding increases in dogs, conception rate declines, sperm count is reduced, litter size decreases, pre- and post-natal survival is lower, and lifespan is shorter. Dogs demonstrate inbreeding depression in the same ways as other mammals and vertebrates in general. I have summarized some data for dogs on the ICB website here, here, and here.)
Okay, heads up if you've drifted off. Here's the punchline:
I have two bucket lists. One for the things I want to experience and accomplish in life, which despite regular culling continues to exceed what I can reasonably expect to do in my time on this earth. The other bucket list is a list of topics related to genetics and breeding dogs that I want to write about. This list gets longer by the day, and I can only hope that at some point it will be so long that I can start tossing off the ones that are so far down the list that I have no hope of ever getting to. This might make the list look shorter, but it won't reduce the importance of addressing those topics.
The myth of hybrid vigor in dogs is a topic I've been putting off, hoping it would fall off the bottom of the list. But it keeps coming up, and the urgency of addressing it keeps smacking me in the face. So it's time.
Let me say first that this will be about the biology of genes. Genetics is complicated, and it's more important that I write something dog breeders will understand than mention all the little nuances that I wouldn't gloss over if I was writing for a scientific audience. The thing for you to understand is that there is a truth, supported by decades of data as well as a scientific explanation that is firmly rooted in our fundamental understandings about the way genetics works. So I'm sure some people will respond with "But..." and bring up something I didn't talk about that they hope will dismiss all of this as nonsense. There is much more we could talk about, but there are no "but"s that will change the simple facts, and don't let anybody try to convince you otherwise who is not prepared to haul out their documentation.
Over and over, I run into discussions about "hybrid vigor" and why (supposedly) it doesn't occur in dogs. The arguments usually center on some discussion about purebred and mixed breed dogs, and the position supported is that purebred dogs are just as healthy as mixed breed dogs. These ideas get very wide and enthusiastic support from dog breeders and even get extended as a reason why Doodles and other deliberate crosses are a disaster. Published studies are pointed to as supporting this, and even people with relevant professional expertise weigh in with support. But as I said before, there is a truth here that we really need to talk about.
Before we can address the hybrid vigor myth, we need to talk about inbreeding. This is going to on a bit, but inbreeding and hybrid vigor (which we're going to refer to with the scientific term "heterosis") are inextricably linked, and we can't adequatly explain heterosis without understanding some basic consequences of inbreeding. So bear with me.
Inbreeding is the mating of related animals. They can be closely related or distantly related, and we might want to distinguish between close inbreeding and "less close" linebreeding, but for genetics it's all inbreeding, and that's what we will call it here.
Related animals are likely to share alleles as a consequence of common ancestors, so mating related animals makes it more likely that offspring will inherit two copies of the same gene. We would refer to the alleles at that locus as homozygous (i.e., the same). If there are two different alleles at a locus, it is heterozygous. As a consequence of simple inheritance then, inbreeding increases homozygosity and reduces heterozygosity.
Animal breeders noticed long ago that although inbreeding had the advantages of improving the predictably and uniformity of offspring, there was also an effect that could be generally described as "loss of vigor" (Wright 1922; Lush 1943; and I discuss this here). These effects could be very subtle and even be overlooked as reflecting the normal variation in the quality of a group of animals, but research over the last 100 years has confirmed that this phenomenon is real (Charlesworth & Charlesworth 1987; Charles & Charlesworth 1999; Charlesworth & Willis 2009). We call it "inbreeding depression".
Inbreeding depression is not an increase in the incidence of genetic disorders of relatively high heritability like PRA or cardiomyopathy or hemolytic anemia. Rather it refers to loss of what biologists call "fitness", which encompasses the breadth of traits that affect an animal's ability to successfully pass its genes on to the next generation. Animals that die before reproducing have a fitness of zero. Animals that successfully reproduce but don't properly care for their offspring, which die as a consequence, also have a fitness of zero. Animals that have a high level of fitness produce offspring that go on to reproduce themselves and thereby perpetuate their genes in the population, and animals that do that less effectively or fail entirely have low or zero fitness.
In the context of breeding animals and plants, when we're talking about inbreeding depression we're usually referring to the collection of traits that affect reproduction and lifespan such as fertility, offspring size, pre- and post-natal mortality, maternal care, resistance to disease, and general "vigor and vitality". These effects have been documented in many thousands of studies and in all manner of organisms, and although there is much yet to be learned about it, there is no debate about the fact that it is a real phenomenon in both wild and domestic animals (Nicholas 1995).
Why do inbred animals have lower fitness? Because inbreeding results in an increase in genomic homozygosity, and homozygosity reduces fitness, resulting in inbreeding depression (Charlesworth & Charlesworth 2009). Homozygosity can reduce fitness because it increases the expression of deleterious recessive alleles, some of which are lethal and can result in death early in embryonic development. Likewise, there can be high levels of homozygosity in many alleles of small effect that control reproduction and other developmentally and physiologically complex processes. Homozygosity also reduces the beneficial effects of "overdominance", in which heterozygosity at a locus is advantageous over homozygosity of either allele ("heterozygote advantage") (Charlesworth & Willis 2009). (I have discussed some interesting examples of heterozygote advantage here.) We could say much more about the genetics of inbreeding depression, and there are some sources in the references at the end that address the details, but these are the basics of what we need to understand about inbreeding depression as it is going to relate to the issue of heterosis.
Of course, it is important to note that inbreeding depression occurs in dogs just as in any other mammal. As the level of inbreeding increases in dogs, conception rate declines, sperm count is reduced, litter size decreases, pre- and post-natal survival is lower, and lifespan is shorter. Dogs demonstrate inbreeding depression in the same ways as other mammals and vertebrates in general. I have summarized some data for dogs on the ICB website here, here, and here.)
Okay, heads up if you've drifted off. Here's the punchline:
| Inbreeding increases homozygosity that results inbreeding depression, with negative effects that we can loosely refer to as "loss of vigor". Heterosis - hybrid vigor - is the reversal of the loss of vigor that defines inbreeding depression as a result of an increase in genetic heterozygosity. |
Increased homozygosity results in inbreeding depression in dogs, so the reduction of inbreeding depression that results from increasing heterozygosity is heterosis. It's as simple as that.
There are a few important points to emphasize. First, the sorts of genetic disorders that breeders commonly need to deal with that result from recessive mutations, such as copper toxicosis, centronuclear myopathy, multi-drug resistance, or exercise-induced collapse are not what we're talking about. Yes, these things can certainly affect a dog's ability to pass on its genes to the next generation, but inbreeding depression is not about a specific disease but rather the steady compromise in functions that can chip away slowly at the health and productivity of populations of animals over the generations. Reversing the effects of inbreeding depression is not about fixing just a gene or two.
Notice that nowhere in here have we talked about hybrid vigor only applying to crosses between species, which is often argued as a way of rendering the topic irrelevant in discussions about dogs. In fact, there is some confusion here about the use(s) of several important terms. What defines a species is its inability to produce fertile offspring with other species, something biologists call "reproductive isolation", which can be a result of anatomy, physiology, geography, or even behavior. Two species don't usually tango. But there are a few animals that we consider separate species that can produce offspring that are healthy but usually sterile, such as the mules produced by crossing a horse with a donkey. Mules are "interspecific" (between species) hybrids. If these hybrids are generally sterile, we're not producing any hybrid vigor when we make these crosses. So the notion that hybrid vigor can't occur in dogs because it applies only to separate species is incorrect.
But we can also talk about the hybrids that are produced by crosses within a species, such as crossing different varieties or genetically distinct subpopulations or lines. These are intraspecific hybrids. When Mendel was sorting out the basic details of inheritance, he was making crosses between different cultivars or strains of peas, producing intraspecific hybrids.
Like Mendel's peas, crosses between dog breeds would also produce intraspecific hybrids, usually referred to as F1 hybrids. If we're working with a breed of purebred dog in which there is inbreeding depression because of increased homozygosity, a cross with another breed will reduce the homozygosity of the offspring and result in hybrid vigor. But in fact, the dogs don't have to be different breeds, they can even be different lines within a breed. If these are populations are prevented from crossing for several generations they will drift apart genetically, and when they are crossed the offspring are likely to be more heterozygous than either parent. In fact, these crosses within breeds are widely used in animal breeding to manage levels of inbreeding and improve the vitality of the stock. (You can read more about this here.)
The notions of inbreeding depression and heterosis are what we call "settled science". The details might change in light of new research or ideas, but there is broad acceptance among scientists that the fundamentals are sound and likely to stand the test of time.
Inbreeding depression and hybrid vigor are predictable and understandable consequences of changes in genetic heterozygosity that can result from particular breeding strategies. Breeders of other domestic animals figured out long ago how to use heterosis to their advantage by deliberately crossing within or across breeds to produce higher levels of heterozygosity in offspring than in the parents. Many long-time dog breeders understand heterosis and use it to good effect in their breeding programs.
So no, hybrid vigor in dogs is not a myth. But why do dog breeders persistently insist that it is?
This topic is on my bucket list. Stay tuned.
There are a few important points to emphasize. First, the sorts of genetic disorders that breeders commonly need to deal with that result from recessive mutations, such as copper toxicosis, centronuclear myopathy, multi-drug resistance, or exercise-induced collapse are not what we're talking about. Yes, these things can certainly affect a dog's ability to pass on its genes to the next generation, but inbreeding depression is not about a specific disease but rather the steady compromise in functions that can chip away slowly at the health and productivity of populations of animals over the generations. Reversing the effects of inbreeding depression is not about fixing just a gene or two.
Notice that nowhere in here have we talked about hybrid vigor only applying to crosses between species, which is often argued as a way of rendering the topic irrelevant in discussions about dogs. In fact, there is some confusion here about the use(s) of several important terms. What defines a species is its inability to produce fertile offspring with other species, something biologists call "reproductive isolation", which can be a result of anatomy, physiology, geography, or even behavior. Two species don't usually tango. But there are a few animals that we consider separate species that can produce offspring that are healthy but usually sterile, such as the mules produced by crossing a horse with a donkey. Mules are "interspecific" (between species) hybrids. If these hybrids are generally sterile, we're not producing any hybrid vigor when we make these crosses. So the notion that hybrid vigor can't occur in dogs because it applies only to separate species is incorrect.
But we can also talk about the hybrids that are produced by crosses within a species, such as crossing different varieties or genetically distinct subpopulations or lines. These are intraspecific hybrids. When Mendel was sorting out the basic details of inheritance, he was making crosses between different cultivars or strains of peas, producing intraspecific hybrids.
Like Mendel's peas, crosses between dog breeds would also produce intraspecific hybrids, usually referred to as F1 hybrids. If we're working with a breed of purebred dog in which there is inbreeding depression because of increased homozygosity, a cross with another breed will reduce the homozygosity of the offspring and result in hybrid vigor. But in fact, the dogs don't have to be different breeds, they can even be different lines within a breed. If these are populations are prevented from crossing for several generations they will drift apart genetically, and when they are crossed the offspring are likely to be more heterozygous than either parent. In fact, these crosses within breeds are widely used in animal breeding to manage levels of inbreeding and improve the vitality of the stock. (You can read more about this here.)
The notions of inbreeding depression and heterosis are what we call "settled science". The details might change in light of new research or ideas, but there is broad acceptance among scientists that the fundamentals are sound and likely to stand the test of time.
Inbreeding depression and hybrid vigor are predictable and understandable consequences of changes in genetic heterozygosity that can result from particular breeding strategies. Breeders of other domestic animals figured out long ago how to use heterosis to their advantage by deliberately crossing within or across breeds to produce higher levels of heterozygosity in offspring than in the parents. Many long-time dog breeders understand heterosis and use it to good effect in their breeding programs.
So no, hybrid vigor in dogs is not a myth. But why do dog breeders persistently insist that it is?
This topic is on my bucket list. Stay tuned.
Charlesworth D & B Charlesworth. 1987. Inbreeding depression and its evolutionary consequences. Ann Rev Ecol Syst 18: 237-268.
Charlesworth B & D Charlesworth. 1999. The genetic basis of inbreeding depression. Genet Res, Camb 74: 329-340.
Charlesworth D & JH Willis. 2009. The genetics of inbreeding depression. Nat Rev Genetics 10: 743-796.
Dickerson, GE. Inbreeding and heterosis in animals. J Anim Sci 1973: 54-77. (pdf)
Lush J. 1943. Animal breeding plans. The Iowa State College Press, Ames, Iowa. (pdf)
Nicholas FW. 1995. Veterinary Genetics. Oxford Science Publications.
Wright S. 1922. Coefficients of inbreeding and relationship. Am Nat 56: 330-338.
Charlesworth B & D Charlesworth. 1999. The genetic basis of inbreeding depression. Genet Res, Camb 74: 329-340.
Charlesworth D & JH Willis. 2009. The genetics of inbreeding depression. Nat Rev Genetics 10: 743-796.
Dickerson, GE. Inbreeding and heterosis in animals. J Anim Sci 1973: 54-77. (pdf)
Lush J. 1943. Animal breeding plans. The Iowa State College Press, Ames, Iowa. (pdf)
Nicholas FW. 1995. Veterinary Genetics. Oxford Science Publications.
Wright S. 1922. Coefficients of inbreeding and relationship. Am Nat 56: 330-338.
