First, a confession. Before I bred animals, I was a scientist. I worked for several years on the interface between chemistry and biology. The work I did necessitated a good working understanding of genetics. From a theoretical, laboratory-based perspective, many scientists would give the generalised advice to practical breeders of animals that inbreeding is always bad and outbreeding is always good. But after 5+ years of breeding animals and observing the results, and talking to others who breed animals and the results they have observed, the reality is a lot more nuanced than this. The next article will be about how inbreeding and outbreeding can be used for the benefit of populations such as breeds historically and in modern times using new tools. The purpose of this article is to explain both terms as a basis for it.
Inbreeding and outbreeding and the related term COI as explained in the earlier articles are a probability-based estimate of the heterozygosity of individual animals using data derived from known relationships and recorded pedigrees. Strictly speaking, it is not correct to use the term incest interchangeably with terms such as inbred, as incest relates to human taboos about sexual contact within relationships that a. may not actually be genetic (historically it has been considered incest to have sexual contact with one's wetnurse or any of her offspring) and b. may apply to situations where offspring are biologically impossible (homosexual relationships between related individuals are considered incest just as much as comparable heterosexual relationships). Inbreeding pertains specifically to offspring and blood relatedness. Inbreeding is also not to be confused with interbreeding, which is used to describe genetic exchange between two populations, and actually more closely approximates outbreeding.
Inbreeding increases the risk of problems arising from homozygosity. Firstly, breeding together animals with genetics in common (which in genetically related animals is more likely than animals chosen randomly) increases the risk that any harmful recessive alleles these animals carry will be doubled up. How, quite, this manifests in practice and whether it can be controlled depends on what sort of harmful recessive alleles are there in the first place, as some recessive diseases are lethal and cause affected offspring to die before birth, or are obvious or lethal shortly after birth, and others are more insidious and cause diseases that are not apparent until later in life. In matings between individuals more distantly related than first cousins (<~6% COI), the risk is only slightly worse than for random pairings, however. Inbreeding over several generations can also result in the classic 'loss of fitness' inbreeding depression wherein factors like birth rate, general health, and longevity suffer. It is not fully understood why this happens, but either an accumulation of less than beneficial recessives or general lack of heterosis throughout the genome seems to be the cause, and it may even be that it is an evolutionary adaptation to prevent loss of genetics in a population. Inbreeding tends to occur in nature quite commonly, and in particular for apex predators it is pretty much unavoidable, and there is emerging evidence that there may be adaptations in place to limit loss of heterosis through inbreeding: some theorise that fertilised eggs inside a bitch are less likely to implant if they are very homozygous, which might explain why some dog breeds with low effective populations produce small litters. However, if inbreeding is done systematically over many generations in a directed way to decrease heterosis, such as the method of mating successive siblings to develop homozygous and genetically near-identical laboratory strains, these adapted defences are overcome and the decks are gradually stacked more and more towards loss of heterosis.
Inbreeding depression in domestic birds is often observed as a reduction in hatchability (eggs develop, but die in the shell before they can hatch), which I have observed with inbred chicken breeds. Indeed in the case of some kinds of bird it is apparently impossible to create inbred strains, because beyond a certain threshold the eggs become entirely unhatchable, and therefore inbreeding is self limiting.
Inbreeding depression is much more widely acknowledged and understood than its inverse, outbreeding depression, which can also be a cause of loss of fitness and genetic disease. Outbreeding depression has probably been known of scientifically as long as has inbreeding depression, but has been the subject of much lesser study. Some of its forms are also rather more complex to understand than inbreeding depression. So what is outbreeding depression, and how does it work?
Scottish Wildcat and Scottish Wildkitten by Peter Trimming
First of all, outbreeding depression does not necessarily apply to some situations that occur in nature whereby subspecies lose their genetic integrity through interbreeding with each other. The most well-known example that people are likely to be familiar with is the loss of the Scottish Wildcat through interbreeding (outcrossing) with the domestic cat population. Obviously this is tragic because the wildcat species will not survive as we know it for posterity to enjoy, but this is not outbreeding depression, because outbreeding depression results in a loss of fitness in the resulting individuals, which the wildcat offspring apparently do not.
Red Dorking cock
Silver-Grey Dorking cock (credit: 3268zauber)
There are a number of different mechanisms by which outbreeding depression can occur, so I am going to start with an illustrative example to explain the most simple one. Dorking chickens are a very rare breed. While I was acquiring some of these chickens, I discovered the hatchability of the eggs was quite poor, which points to inbreeding depression. As I could not find sufficient unrelated sources of red Dorkings of acceptable type, I acquired a silver Dorking hen and mated her to my red Dorking cock. A cockerel of good type hatched, but with one fault: it is neither red nor silver. The colour I would describe as being 'gold' which is not a correct colour for a Dorking, but makes perfect sense to someone who understands the genetics of colour inheritance in chickens. Since the breed standard for the red and silver Dorkings is identical apart from the colour, I can breed this gold cockerel to my red hens and recover correct red offspring, and this is a good way to increase the genetic diversity of the red variety.
'gold' Dorking cockerel (heterozygous intermediate of above)
Obviously, for a domestic animal to be an incorrect colour does not confer a survival disadvantage, but in a wild species, a heterozygous intermediate that is a different colour to either homozygous extreme could turn out to be ill-adapted to its environment. Suppose two subspecies live in a mountainous terrain. One has evolved a dense white pelt to help it to camouflage and keep warm in the harsh conditions on the snow-covered peaks. The other lives at the foot of the mountains in a thick jungle, and has a black, sleek coat to camouflage it in its own environment. Suppose they wandered from their normal territory and mated, and produced offspring that had a dingy greyish-beige coat of intermediate density. These animals would be unlikely to thrive in either the jungle environment or the exposed mountain, and in this case would be considered outbreeding depression, as the ability of the offspring to survive in their environment is compromised.
A second way in which outbreeding depression can occur is when animals who have evolved along very different, often mutually exclusive lines breed together and the genes that have long evolved in isolation are combined and no longer match up. Eventually, populations evolving in isolation tend to become so different that they can no longer interbreed: physical mating becomes impossible, sperm and egg no longer recognise each other, or zygotes (fertilised eggs) cannot divide. Before this point of no return is reached, outcrossing of this sort can produce anything from high infant mortality and low conception rates, to deranged behaviour and weird traits not seen in either parent's line, and to offspring that are incapable of reproduction. In the plant kingdom, we often enjoy these infertile cross-bred specimens in our gardens, since their potential for invasion is self-limiting and they can show bizarre colours and forms not found in nature. But for a species in the wild, infertile hybrids are an evolutionary cul-de-sac that can spell disaster. Infertile hybrids compete for resources yet contribute nothing to posterity. In the cases of animals that have developed evolutionary strategies that invest a great deal of effort in rearing offspring, such as mammals who give birth to one offspring and care for it for a year or more, or birds who form monogamous pairs, infertile hybrids can seriously impact the reproduction rate and even push species towards extinction.
The third form of outbreeding depression I am going to talk about is probably the most difficult to understand. It explains how crossing two unrelated individuals can sometimes appear to cause genetic diseases that did not exist in either parent line. I am going to use another anecdote, and this anecdote is fictitious, but plausible, and may well have happened before:
Once upon a time, in a faraway country, there existed a great landrace of dogs prized for their beautiful tails. This landrace was formalised into a breed in the Victorian era along with many others. Then, the wonderful exotic country was torn apart by war and insurrection and the originators of the breed disappeared. The breed survived in those countries where it had been formalised, but it suffered through both world wars, and eventually the effective population size became diminished, and some popular sires became very influential, and eventually because of all of this, it came to be that the breed was afflicted with a genetic disease that caused some of the dogs' beautiful tails to fall off. Nobody knew how to prevent this from happening, and all lines were affected. Now, onto the scene come two luminaries of the breed, Mrs A and Mr B. In many ways they are much alike, but they are rivals, and so they loathe each other with a burning passion and will not collaborate. Mrs A and Mr B establish kennels at opposite ends of the country, and they both start to breed and select aggressively to eradicate the tail-fall-off gene. They start from stock that is pretty much the same as everyone else's, and because they are able to breed and keep a large number of dogs and discard those that are not suitable, they both succeed. And everyone flocks to buy dogs from Mrs A and Mr B, but because both of them only sell dogs with a contract saying they must not be bred from, and they never collaborate, the lines stay separate and exclusive to their developers.
Unfortunately for this breed of dogs, nothing ever stays the same (apart from Mrs A and Mr B's hatred of each other and refusal to work together). As time goes on, it becomes unpopular for dog breeders to use the kennel model. Mrs A gets older, reduces her numbers, and eventually, her closed bloodline collapses in on itself, and unable to care for dogs any more, she hands over her last few ageing inbred dogs to her daughter and retires. Mr B clings tenaciously to his breeding programme even though his health is failing and he can't care for his dogs adequately any more. Eventually a complaint is made, and the police go to his house and discover malnourished dogs and decrepit Mr B living in filth. Mr B ends up in a nursing home and the dogs are turned over to a shelter that promptly removes their reproductive organs and sells them as pets, apart from a handful that Mr B's son manages to get to in time and make a deal to get them back.
The daughter and son of A and B meet and decide it is time to put aside the personal disagreements of their parents and do what is best for the breed. Neither bloodline is now genetically diverse enough to survive much longer in isolation, so they breed together A and B's dogs, and puppies are born. The puppies are wonderful! Fantastic breed type, and with vigour that comes from new heterosis that had been lost for generations of close breeding within the two lines. And then all of the puppies' tails fall off! Distraught, they try more matings, but still pups are born that exhibit tail-fall-off syndrome, and by now the original dogs remaining from the lines have either passed away naturally or are too old to breed. They try inseminating one of the bitches whose tail has fallen off with the last straw of semen from one of Mr B's dogs, and some of the puppies' tails don't fall off, but when they breed these offspring with tails, some of the pups' tails still fall off. It seems the lines do not work the same way when they are bred together.
The son and daughter of the two great luminaries of the breed become disillusioned and give up. A few generations later, the breed numbers decline so much because of bad press about tail-fall-off syndrome that the breed becomes unviable, and ultimately extinct. So ends this lovely breed of dog.
So what happened? To understand, we have to understand that unless we are using actual genetic tests, we can't select for actual genetics. The only things we CAN select for are the effects of genes as a whole. We can only conclude that the selection of Mrs A and Mr B for dogs that did not have or produce tail-fall-off syndrome did not select for the same genes in both cases. Perhaps tail-fall-off syndrome is caused by a dominant allele at a single locus, and Mrs A selected for dogs whose tails did not fall off and whose relatives' tails did not fall off until the recessive non-faulty allele became fixed in her population, whereas Mr B selected the same, but a recessive allele at an entirely separate locus that counters the effects of the first gene was the result in his case, and he happened to fix this in his population so it became immune to the effect of the tail-fall-off gene despite all of his dogs having at least one copy of it. The genetics to cause tail-fall-off syndrome were still there, and crossing together the bloodlines revealed them.
When a population is subjected to selection, it reaches a stable state when all the genes within its genome interact in such a way to generate a phenotype that fits the environment it has been selected for. This environment could be a natural environment, or an artificial one such as a breed standard or the absence of diseases. An outcross can destabilise these genes by disrupting the genetic environment needed for the genome to function properly as a whole and recombining genes that don't quite work together. Note that this example made up of alleles at two loci, one dominant and one recessive, is just the most simple example, and there are many other possibilities involving several loci perhaps with multiple alleles and different effects. If lines become fixed at certain loci for dominant alleles as a different example, then the first generation outcross would be normal, and only in later generations would the trait begin to manifest -- and if the outcross had been followed by a linebreeding, this might even be mistaken for the result of a simple recessive.
How this affects wild and artificial populations
Nature seems to have evolved a few counters to prevent serious problems arising from individuals mating from other individuals who are either very different to each other or very similar. Different species often can't physically mate or exude different mating pheromones that are not cross-compatible, and there seems to be a universal sexual revulsion between those we are too familiar with. Inbreeding and outbreeding problems on lesser levels can still affect natural populations. In many cases, where animals adapted to different environments come into contact and outcross with each other, the offspring don't live long enough to reproduce due to unsuitability for either environment, or are infertile. In others, some of them are reabsorbed back into one of the parent populations, and selection over a number of generations gradually removes any immediately deleterious combinations of genes. Sometimes this can be beneficial in that it introduces new genetics and benefits adaptation. Occasionally an influx of foreign genetics can reduce breeding or fitness to an extent that can decimate or even wipe out a species. Populations that become too inbred can likewise reach the point of genetic collapse and become extinct. Short-term inbreeding as a response to selection pressure may benefit a population by increasing the proportion of adaptive genes in a population.
In artificial populations, i.e. breeds, outbreeding depression is usually unlikely within that population (breed), with the possible exception of the third example shown above, where there has been hard selection for particular traits in isolation. Wrong colours do sometimes occur in breeds, either due to recessive genes or particular combinations at different loci, and although they are generally not liked, they are not usually harmful. When different breeds are mixed together, unpredictable results can occur whereby the offspring don't possess the traits of either parent strain due to differing genotypes, even if they have been selected for similar phenotypes. In the cases of breeds that were domesticated independently of each other from similar wild ancestors, there may be a reversion to the appearance and behaviour of the wild type in their offspring. In breeds that have been purposely created from a series of outcrosses of disparate stock, it may even be that unresolved genetic conditions may occur as an outbreeding 'hangover' of the original outcrosses.
Turkey hen from outcross between heritage Bourbon Red stag and commercial-type white hen
A somewhat unusual breed of animal in this respect is that of domestic turkeys. There are no breeds of domestic turkeys; just 'varieties' even though there may be great physical differences. Two years ago, I gave a heritage turkey stag to a neighbour who rears white commercial turkeys for slaughter, and the neighbour kept one hen from the stock they had bought as company for this turkey. Commercial turkeys are in every way an extreme and artificial animal. Their bodies are distorted to produce large amounts of breast meat, and they can't fly and the stags can't mate. In contrast, heritage turkeys resemble their wild ancestors. Last year, the neighbours gave me 12 eggs from these turkeys. Most of the eggs were fertile, but only three of them hatched, which under any other circumstances would lead me to suspect inbreeding depression. I kept two of the hen turkeys that hatched and put them in a pen with an unrelated heritage stag. This year I am discovering continuing adverse effects such as eggs that don't hatch and poults that fail to thrive and die. Normally, turkeys are one of the easiest species to hatch and rear, and all my eggs and poults from my other turkeys (which are laid and incubated in exactly the same conditions) are doing fine as usual.
Inbreeding depression can be removed in a single generation by use of an outcross. As illustrated by the above example, outbreeding depression is a problem not so easily solved. Genetics that clash with the rest of the genome persist through the generations, and the only way to remove them is through rigorous selection and a lot of breeding until the population reattains a stable state. The next article will be about how modern techniques can be used to control inbreeding and outbreeding and limit adverse effects resulting from them.
Thriving heritage turkey poults, various colour morphs
I'm going to repeat something I wrote above, because I feel it's important for any animal breeder to acknowledge this limitation. UNLESS YOU ARE USING A GENETIC TEST, YOU CANNOT SELECT GENETICS. YOU CAN ONLY SELECT BASED UPON PHENOTYPE WHICH IS CONTROLLED BY THE GENOTYPE AS A WHOLE (and potentially also by external factors which might have nothing to do with genetics). 2+2=4, but so does 3+1, and 1x4, and 1,209-1,205. If you can only observe the result but not see the mechanism by which is was reached, you can only select the result and not the mechanism.
Peery Wildlife Ecology & Conservation Lab -- paper about the harm outbreeding and hybridisation can do to wild populations