NOTE: This is a revision of our original post, because a mistake on our part was pointed out by a commenter, to whom we offer thanks. Our main point hasn't changed....unless there are still misperceptions on our part.
BBC Earth headline: "Inbreeding Makes Mountain Gorillas Genetically Healthy." We are so tempted to add an exclamation point to that, but we won't. Anyway, you know it's there, whether we add it or not. Everyone 'knows' that inbreeding is bad; what a juicy story!
And, to summarize, the story is this: Mountain gorillas are an endangered species, surviving now in just two small groups in central Africa, a total population of only about 800 individuals. Their numbers had fallen to just under 300 in the 1980's, for multiple reasons including poaching and loss of habitat, but Diane Fossey made their conservation her life's work, and the population more than doubled since its lowest point.
Location of eastern and western gorillas; Xue et al., Science 2015
But, their small numbers led to extensive inbreeding, which is always worrisome to conservationists because it may reduce a population's ability to adapt to changing environments. But, the BBC writes:
Now scientists have discovered inbreeding has actually benefitted mountain gorillas by removing many harmful genetic variations. They are also genetically adapted to living in small populations.And,
Fewer harmful genetic mutations, which stop genes functioning and can cause serious health conditions, were found in the mountain gorilla population than in the western gorilla populations.Ok, let's step over to the actual paper ("Mountain gorilla genomes reveal the impact of long-term population decline and inbreeding," Xue et al.), in Science last week, to get the story without the go-between. So, the investigators sequenced the whole genomes of 13 eastern gorillas, including seven mountain gorillas and six eastern lowland gorillas. They compared these sequences with published sequences of lowland gorillas further west, and found lower genetic diversity in both the mountain and lowland gorillas from the east, which they report as consistent with the smaller population sizes there. Their analysis, they report, confirms that the eastern lowland and mountain gorillas are two genetically distinct populations. Genome wide linkage disequilibrium was higher in the eastern gorillas than the western, evidence of different demographic histories of these populations, and suggesting a recent population bottleneck in the eastern gorillas.
|Foraging gorilla, Congo; Wikipedia, Pierre Fidenci|
In eastern gorillas, chromosomes were found to be homozygous across 34 to 38% of their length, while in western lowland gorillas, they were 13% homozygous, indicating that the eastern gorillas have a recent history of several generations of close inbreeding. Xue et al. also report that the eastern and western populations diverged perhaps 150,000 years ago, with no mating history in the last 20,000 years or so. And, overall, it seems that gorilla population sizes have been small for thousands of years, and thus probably have been inbreeding for all of that time.
Again comparing mountain with lowland gorillas, Xue et al found no evidence for natural selection or adaptation favoring functional genes in either group.
Such adaptation might be expected from the fact that mountain gorillas range over high altitudes (1500 to 4000 m), with consequences for diet, morphology, and physiology. However, we found no significant enrichment in any functional category of genes, although there are interesting examples related to nervous system morphology, immunoglobulin quantity, and red blood cell morphology. Mountain gorillas carry a significant excess of variants in genes associated with blood coagulation in humans (fig. S21), perhaps linked to high-altitude living. We also identified variants associated with cardiomyopathy, including in one deceased individual (Kaboko) in whom post mortem analysis revealed evidence of muscular hypertrophy. Cardiovascular disease has been identified as a notable cause of death in captive western lowland gorillas.With respect to unfavorable effects of inbreeding, the authors report the opposite, saying that inbreeding seems to have purged deleterious mutations from the genome. They suggest that gorillas have found workarounds for inbreeding effects, as well, such as by "natal dispersal and gene flow between isolated populations."
Xue told the BBC that gorillas have been coping with small populations for thousands of years, and,
"While comparable levels of inbreeding contributed to the extinction of our relatives, the Neanderthals, mountain gorillas may be more resilient. There is no reason why they should not flourish for thousands of years to come."No reason?
But, we can think of a number of reasons. The Ebola virus has been devastating to chimps and gorillas, wiping out 95% of some groups of gorillas in which it has spread. And, there's always the possibility that other infectious diseases may emerge, or reach these animals, and be equally, or even more devastating.
And, poaching continues to be a problem, and hunting for bushmeat. Loss of habitat continues to be a problem. Climate change will surely have consequences for these animals. As with any other animal, including humans, environmental change and its consequences are unpredictable. Whether or not any species has the genetic wherewithal to adapt to that change is unpredictable; it's impossible to know what any single gene will do in every possible environment, never mind what every gene, and every genetic interaction will do. This is, of course, true with respect to predicting our own futures from our genomes as well.
What is 'inbreeding' and what does it mean?
There are several things about this paper aside from the apparent obliviousness of the research report to the real threat to gorilla 'fitness', namely that they're widely projected to become extinct because of human incursion and predation, in addition to disease. We might also ask, if the western gorillas have so little relative homozygosity, why they aren't plagued with the sorts of defects that the easterners have already purged, and on the verge of collapse -- or long gone?
The answer is that both populations (not just the eastern) did well enough to be here today. Both low and high homozygosity are obviously good enough, because neither wiped out either population structure in their past. So why tell the story as if one way's better? It seems to be the tired old evolutionary trope that we cannot seem to escape: To be different from is to be better than, to evolve away from is because it's a better way. But, mutation is always happening, genetic drift is always happening, and if a variant works, it works. It isn't necessarily selected because it's better, or more adaptive, than anything that came before.
This paper is in a sense an exaggeration of, and in a way confusion about inbreeding and its effects. There are several meanings of 'inbreeding' that are relevant here** . The classical meaning refers to mating with close relatives relative to random-mating. The issue there is the classical one of increased incidence of recessive disorders with inbreeding. In that context, the probability of an allele being homozygous more than just by chance: if the latter is p^2 when there is random mating, the former is p^2 + Fp(1-p), where p is the frequency of the variant in question, and F is the excess probability of being homozygous due to non-random mating. That may be because of socially constructed preferential kin-mating or just a deviation from random mating. In many, if not historically most, human populations, mating was prescribed as to be between cousins of various types. If variants are harmful but recessive so that their harm is only seen in homozygotes (both copies in a person being defective), then mating between close relatives can increase the frequency of such events, and the loss of the harmful variant from the population, but of course only at the expense of the carriers of those harmful genotypes. One can argue that if something like close-relative mating were so dangerous it would never have evolved to be, in a sense, the ancestral human way as it has. Or, one can note that the reason for local group endogamy or exogamy (how mates are chosen in any population, human or otherwise) has to do with social structure, resource distribution, and control of internecine and intergroup strife--not because of disease genes.
The authors appear not to have done this kind of calculation, however, and samples would have been too small for it to make sense. Instead, they looked along the genome to see what fraction was homozygous (that is, variant sites along the region in the sequenced animals). This reflects a different use of the term 'inbreeding', and we think what this paper is referring to, is the rise in homozygosity due to genetic drift in small populations. In a small population, rarer alleles (genetic variants) are lost more rapidly from the population, mainly just by chance. Homozygosity at a given site is an inevitable reflector of population size, and in a small population the region of a chromosome that is homozygous (not varying) would be larger than in a large outbred population. That is not an automatic indicator of a history of loss of harmful mutations, recessive or otherwise. In any population harmful variants have a shorter staying time than helpful ones, but their duration depends on many different factors that can't be inferred from the stretches of homozygosity alone.
Do western lowland gorillas, with their lack of a history of 'inbreeding' as presented by this story, show some detectable load of sub-par individuals? If so, that would be relevant news. In fact, both groups have coefficients higher than human cousins relative to each other, as a commentary on this paper notes. But so what? In fact, and perhaps to the contrary, being too inbred in the small-population sense could, as far as just-so stories go, mean there would not be enough variation in the population to respond to environmental challenges.
What the study does no doubt actually show is that the two gorilla populations have had different demographic histories. That is ecologically interesting and perhaps useful for understanding wildlife conservation issues. But in itself it says basically nothing about purging harmful variation except that it would be somewhat faster, on average, in one group than the other -- but only slightly so, because if that were not the case the burden of loss could have threatened the very survival of the group in the past so that it never made it to the present, which obviously isn't the case. 'Inbreeding' in headlines may have a juicy sound and catch the lascivious eye, and that's why the news media go for it so readily.
It should also be noted that extensive, detailed, biomedically documented studies in human isolate populations have found each to have particular instances of elevated recessive diseases or other traits due to inbreeding effects, but the overall burden of genetic disease has not been particularly increased, if at all.
***The often and perhaps still confusing issue of inbreeding have been clarified long ago, e.g., by Albert Jacquard in 1975, in J. Theoretical Biology, "Inbreeding: one word, several meanings", by various wrtiting of Warren Ewens back in the 70s, or see Templeton and Read, Conservation Genetics, 1994; they are discussed in any good population genetics text.