Is a First Human Pair Possible or Impossible?
Ann Gauger
Sometimes the claims that scientists make go beyond what can be definitively established. They may overestimate the sensitivity of their analytical methods, or engage in somewhat circular reasoning. These kinds of things are hard for laypeople to detect; even scientists trained in a different field may not recognize there is a problem. That’s why it is enormously useful to have important claims evaluated by someone who is knowledgeable in the particular subject under dispute, especially if the dispute matters to a great many people.
Richard Buggs, Reader at Queen Mary University of London, is a well-respected geneticist, with numerous papers published in molecular ecology, genomics, and molecular evolution. He knows something about population genetics. In a post on October 28 on the Nature Ecology and Evolution community website, Buggs questioned assertions made by Professor Dennis Venema (Trinity Western University) in his book Adam and the Genome, concerning the possibility of a first human pair. He begins thusly:
Does genomic evidence make it scientifically impossible that the human lineage could have ever passed through a population bottleneck of just two individuals? This is a question I am asked semi-frequently by religious friends….
The issue is this. Believers in Abrahamic religions who accept evolution often combine it with belief that all humans have descended from a single couple. Until now, many have assumed that this belief is compatible with evolution and mainstream science.
This needs to change, according Christian biologist Dennis Venema writing in the 2017 book Adam and the Genome. Chapter 3 of this book claims that three population genetic studies give independent estimates that the population size of humans has never dropped below around 10,000 individuals. Venema declares that a bottleneck of two is impossible, and this is a fact of comparable scientific certainty to heliocentrism. He gives his Christian readers a stark choice between embracing mainstream science, or sticking with untenable beliefs about an ancestral couple.
Buggs finds himself unable to agree with such a dogmatic statement.
This is fine, so long as mainstream science really is showing that a single-pair bottleneck somewhere in the history of humankind is an absolute impossibility. But having looked at the evidence that Venema describes and cites, I am not yet convinced. I can’t echo him and say to someone who believes in an extreme human population bottleneck that they are against science.
His article goes through the arguments that Venema addresses in his book, and shows for each why it is impossible to rule out the possibility of a first pair as the origin of humanity.
Reduction in Genetic Diversity
Venema argues that having a single pair as the starting point for humanity would cause an extreme bottleneck, leading to an extreme loss in genetic diversity. (He assumes humanity is descended from ape-like ancestors that are the source of that diversity.) On the face of it, it seems reasonable that such a bottleneck in the human lineage would cause an extreme reduction in genetic diversity. But not all bottlenecks are the same. Bottlenecks that last a long time do eliminate diversity, but short sharp ones may not, such as would be the case for a single pair at the start of humanity.
[P]opulation geneticists (M. Nei, T. Maruyama and R. Chakraborty 1975 Evolution, 29(1):1-10) showed that even a bottleneck of a single pair would not lead to massive decreases in genetic diversity, if followed by rapid population growth. When two individuals are taken at random from an existing large population, they will on average carry 75% of its heterozygosity (M. Slatkin and L. Excoffier 2012 Genetics 191:171–181). From a bottleneck of a single fertilised female, if population size doubles every generation, after many generations the population will have over half of the heterozygosity of the population before the bottleneck (Barton and Charlesworth 1984, Ann. Rev. Ecol. Syst. 15:133-64). If population growth is faster than this, the proportion of heterozygosity maintained will be higher.
Buggs then goes on to address a related subject called allelic richness, or how many variants of each gene there are. Venema states the problem as follows:
Taking into account the human mutation rate, and the mathematical probability of new mutations spreading in a population or being lost, these methods indicate an ancestral population size for humans right around that 10,000 figure. In fact, to generate the number of alleles we see in the present day from a starting point of just two individuals, one would have to postulate mutation rates far in excess of what we observe for any animal.
How does Buggs respond?
We need to bear in mind that explosive population growth in humans has allowed many new mutations to rapidly accumulate in human populations (A. Keinan and A. G. Clark (2012) Science 336: 740-743). Hyper-variable loci like MHC genes or microsatellites have so many alleles that they seem to defy the idea of a single couple bottleneck until we consider that they have very rapid rates of evolution, and could have evolved very many alleles since a bottleneck.
Linkage Disequilibrium Within Populations
Linkage disequilibrium (LD) is a measure of how much recombination has occurred between sites on a chromosome, and because of mathematical relationships between LD and population size, can be used to estimate the size of a population at a particular time. Venema chose to use an LD study (Tenesa et al. “Recent Human Effective Population Size Estimated from Linkage Disequilibrium,” Genome Research 17: 520–26) to argue that we could never have come from just two. As Venema says:
The researchers found that, during this period [200,000 years ago], humans living in sub-Saharan Africa maintained a minimum population of about 7,000 individuals, and that the ancestors of all other humans maintained a minimum population of about 3,000 — once again, adding up to the same value other methods arrive at.
Buggs responds:
This is a rather inaccurate presentation of the paper. The paper’s discussion starts with the sentence: “Overall, the estimates of Ne [effective population size] appear to be much lower than the usually quoted value of 10,000”. It seems to me that the paper gives no warrant for Venema’s addition of effective population sizes above and below the Sahara, as it explains that the non-sub-Saharan populations contain a “subset of the amount of genetic variation present in the African population” due to an out-of-Africa expansion. It is the ancestral sub-Saharan estimate that therefore is of main interest to us. The mean estimated Ne for this population among chromosomes is 6286, with a standard deviation of 1357.
This study depends critically on knowing the recombination rate of the populations. Recombination rate is used both to calculate effective population size (from LD) and to estimate the time point that this is being measured for (from distance between loci). But the main method used to estimate the recombination rate by the authors is patterns of LD. Linkage disequilibrium patterns are also being used to calculate the effective population sizes given a known recombination rate. A degree of circular reasoning seems to be inevitable here. When the authors use a slightly different method to estimate recombination rate (which also relies upon measures of LD), all their estimates of Ne dropped by a mean of 27%. Thus, with the best will in the world, all we have here are ballpark figures for past effective population sizes. I am sure the authors of the study would not view their results as being of equivalent certainty to heliocentrism.
Obviously, however, the paper at no point gives an effective population size estimate as low as two individuals. Does this therefore disprove the hypothesis of a bottleneck of two? I don’t think so, because such a scenario is simply not on the radar of the methods employed. The methods assume that the populations at any given time point are at equilibrium and not expanding exponentially (the authors deliberately exclude the last 10,000 years from this analysis as they know that exponential population growth has occurred in this timeframe). It is hard to see how they could pick up on a short, sharp bottleneck even if one had happened. It would be nice to see this modelled, just to check.
Even if the results of this study are entirely correct, the authors do not make any statements about population size more than 200,000 years ago. This would appear to leave open the possibility of a bottleneck in the previous 5.8 million years.
PSMC Method
The pairwise sequentially Markovian coalescent model (PSMC) is used to analyze single genomes to infer past effective population sizes from patterns of heterozygosity. The first paper to do so was Li and Durbin 2011 (“Inference of Human Population History from Individual Whole-Genome Sequences” Nature 475: 493– 96). Buggs explains:
When run on human genomes, these analyses did not drop below an Ne [effective population size] of 5,700 for African individuals. Does this prove that a sudden, short bottleneck never happened? I don’t think so. Because a single couple can carry with them 0.75 of the heterozygosity of their ancestral population, we would not expect an extreme number of coalescence events at the bottleneck. Furthermore, those that are there were would be smeared out over a long period of time around the bottleneck.
Li and Durbin themselves acknowledge that their technique cannot detect short sharp bottlenecks.
…simulations did, however, reveal a limitation of PSMC in recovering sudden changes in effective population size. For example, the instantaneous reduction from 12,000 to 1,200 at 100 kyr ago in the simulation was spread over several preceding tens of thousands of years in the PSMC reconstruction.
Buggs concludes:
Thus I cannot see that PSMC analyses (many more of which have been done on human genomes since the original paper by Li and Durbin) can be cited as rigorously disproving a short, sharp bottleneck.
Incomplete Lineage Sorting
Short and sweet: incomplete lineage sorting doesn’t matter because it all happened before the human lineage was established.
Venema makes an argument based on incomplete lineage sorting among humans, apes and gorillas, which gives a large estimated effective population size. This argument is not relevant if we are only interested in the human lineage (the occurrence of ILS does not require maintenance of large populations sizes in every lineage after speciation and so does not exclude a bottleneck in the exclusively human lineage).
Conclusion
None of the methods that Venema cites are able to address the problem of the existence of a first pair. Either they are insensitive to short sharp bottlenecks (reduction in genetic diversity, PMSC) or they are not designed to ask the questions at hand, and even engage in somewhat circular reasoning (linkage disequilibrium, incomplete lineage sorting), or they neglect the fact of explosive population growth and high rates of mutation accumulation (allelic richness). It is not to say that these papers are bad, rather they do not address the possibility of a short sharp bottleneck. For that a new approach is needed.
In closing it is best to let Buggs speak for himself:
The question asked by my religious friends is different to the questions being asked in the studies discussed above. My religious friends are not asking me if it is probable that humans have ever passed through a bottleneck of two; they are asking me if it is possible. None of the studies above set out to explicitly test the hypothesis that humans could have passed through a single-couple bottleneck. This is what we need to nail this issue down.
I would very much appreciate feedback from scientific readers of this blog. I have dealt with arguments made in a single book chapter, that has addressed this issue more directly than any other source I have come across. The author, Dennis Venema, is the go to expert on this issue within the organisation BioLogos, set up by Francis Collins (now director of NIH) to explore science-faith issues, so he ought to know what he is talking about. However, there may well be other, perhaps better, arguments that Venema has not made and I have therefore not interacted with.
If I am missing something, then I would very much like to know. Whilst this issue may seem trivial to many readers, for large numbers of religious believers in the world, this is a critical issue. Do they really face a binary choice between accepting mainstream science and believing that humans have, at some point in their history, all descended from a single couple? I am open to the possibility that they do face this dilemma, but I need more evidence before I am persuaded.
Ann Gauger
Sometimes the claims that scientists make go beyond what can be definitively established. They may overestimate the sensitivity of their analytical methods, or engage in somewhat circular reasoning. These kinds of things are hard for laypeople to detect; even scientists trained in a different field may not recognize there is a problem. That’s why it is enormously useful to have important claims evaluated by someone who is knowledgeable in the particular subject under dispute, especially if the dispute matters to a great many people.
Richard Buggs, Reader at Queen Mary University of London, is a well-respected geneticist, with numerous papers published in molecular ecology, genomics, and molecular evolution. He knows something about population genetics. In a post on October 28 on the Nature Ecology and Evolution community website, Buggs questioned assertions made by Professor Dennis Venema (Trinity Western University) in his book Adam and the Genome, concerning the possibility of a first human pair. He begins thusly:
Does genomic evidence make it scientifically impossible that the human lineage could have ever passed through a population bottleneck of just two individuals? This is a question I am asked semi-frequently by religious friends….
The issue is this. Believers in Abrahamic religions who accept evolution often combine it with belief that all humans have descended from a single couple. Until now, many have assumed that this belief is compatible with evolution and mainstream science.
This needs to change, according Christian biologist Dennis Venema writing in the 2017 book Adam and the Genome. Chapter 3 of this book claims that three population genetic studies give independent estimates that the population size of humans has never dropped below around 10,000 individuals. Venema declares that a bottleneck of two is impossible, and this is a fact of comparable scientific certainty to heliocentrism. He gives his Christian readers a stark choice between embracing mainstream science, or sticking with untenable beliefs about an ancestral couple.
Buggs finds himself unable to agree with such a dogmatic statement.
This is fine, so long as mainstream science really is showing that a single-pair bottleneck somewhere in the history of humankind is an absolute impossibility. But having looked at the evidence that Venema describes and cites, I am not yet convinced. I can’t echo him and say to someone who believes in an extreme human population bottleneck that they are against science.
His article goes through the arguments that Venema addresses in his book, and shows for each why it is impossible to rule out the possibility of a first pair as the origin of humanity.
Reduction in Genetic Diversity
Venema argues that having a single pair as the starting point for humanity would cause an extreme bottleneck, leading to an extreme loss in genetic diversity. (He assumes humanity is descended from ape-like ancestors that are the source of that diversity.) On the face of it, it seems reasonable that such a bottleneck in the human lineage would cause an extreme reduction in genetic diversity. But not all bottlenecks are the same. Bottlenecks that last a long time do eliminate diversity, but short sharp ones may not, such as would be the case for a single pair at the start of humanity.
[P]opulation geneticists (M. Nei, T. Maruyama and R. Chakraborty 1975 Evolution, 29(1):1-10) showed that even a bottleneck of a single pair would not lead to massive decreases in genetic diversity, if followed by rapid population growth. When two individuals are taken at random from an existing large population, they will on average carry 75% of its heterozygosity (M. Slatkin and L. Excoffier 2012 Genetics 191:171–181). From a bottleneck of a single fertilised female, if population size doubles every generation, after many generations the population will have over half of the heterozygosity of the population before the bottleneck (Barton and Charlesworth 1984, Ann. Rev. Ecol. Syst. 15:133-64). If population growth is faster than this, the proportion of heterozygosity maintained will be higher.
Buggs then goes on to address a related subject called allelic richness, or how many variants of each gene there are. Venema states the problem as follows:
Taking into account the human mutation rate, and the mathematical probability of new mutations spreading in a population or being lost, these methods indicate an ancestral population size for humans right around that 10,000 figure. In fact, to generate the number of alleles we see in the present day from a starting point of just two individuals, one would have to postulate mutation rates far in excess of what we observe for any animal.
How does Buggs respond?
We need to bear in mind that explosive population growth in humans has allowed many new mutations to rapidly accumulate in human populations (A. Keinan and A. G. Clark (2012) Science 336: 740-743). Hyper-variable loci like MHC genes or microsatellites have so many alleles that they seem to defy the idea of a single couple bottleneck until we consider that they have very rapid rates of evolution, and could have evolved very many alleles since a bottleneck.
Linkage Disequilibrium Within Populations
Linkage disequilibrium (LD) is a measure of how much recombination has occurred between sites on a chromosome, and because of mathematical relationships between LD and population size, can be used to estimate the size of a population at a particular time. Venema chose to use an LD study (Tenesa et al. “Recent Human Effective Population Size Estimated from Linkage Disequilibrium,” Genome Research 17: 520–26) to argue that we could never have come from just two. As Venema says:
The researchers found that, during this period [200,000 years ago], humans living in sub-Saharan Africa maintained a minimum population of about 7,000 individuals, and that the ancestors of all other humans maintained a minimum population of about 3,000 — once again, adding up to the same value other methods arrive at.
Buggs responds:
This is a rather inaccurate presentation of the paper. The paper’s discussion starts with the sentence: “Overall, the estimates of Ne [effective population size] appear to be much lower than the usually quoted value of 10,000”. It seems to me that the paper gives no warrant for Venema’s addition of effective population sizes above and below the Sahara, as it explains that the non-sub-Saharan populations contain a “subset of the amount of genetic variation present in the African population” due to an out-of-Africa expansion. It is the ancestral sub-Saharan estimate that therefore is of main interest to us. The mean estimated Ne for this population among chromosomes is 6286, with a standard deviation of 1357.
This study depends critically on knowing the recombination rate of the populations. Recombination rate is used both to calculate effective population size (from LD) and to estimate the time point that this is being measured for (from distance between loci). But the main method used to estimate the recombination rate by the authors is patterns of LD. Linkage disequilibrium patterns are also being used to calculate the effective population sizes given a known recombination rate. A degree of circular reasoning seems to be inevitable here. When the authors use a slightly different method to estimate recombination rate (which also relies upon measures of LD), all their estimates of Ne dropped by a mean of 27%. Thus, with the best will in the world, all we have here are ballpark figures for past effective population sizes. I am sure the authors of the study would not view their results as being of equivalent certainty to heliocentrism.
Obviously, however, the paper at no point gives an effective population size estimate as low as two individuals. Does this therefore disprove the hypothesis of a bottleneck of two? I don’t think so, because such a scenario is simply not on the radar of the methods employed. The methods assume that the populations at any given time point are at equilibrium and not expanding exponentially (the authors deliberately exclude the last 10,000 years from this analysis as they know that exponential population growth has occurred in this timeframe). It is hard to see how they could pick up on a short, sharp bottleneck even if one had happened. It would be nice to see this modelled, just to check.
Even if the results of this study are entirely correct, the authors do not make any statements about population size more than 200,000 years ago. This would appear to leave open the possibility of a bottleneck in the previous 5.8 million years.
PSMC Method
The pairwise sequentially Markovian coalescent model (PSMC) is used to analyze single genomes to infer past effective population sizes from patterns of heterozygosity. The first paper to do so was Li and Durbin 2011 (“Inference of Human Population History from Individual Whole-Genome Sequences” Nature 475: 493– 96). Buggs explains:
When run on human genomes, these analyses did not drop below an Ne [effective population size] of 5,700 for African individuals. Does this prove that a sudden, short bottleneck never happened? I don’t think so. Because a single couple can carry with them 0.75 of the heterozygosity of their ancestral population, we would not expect an extreme number of coalescence events at the bottleneck. Furthermore, those that are there were would be smeared out over a long period of time around the bottleneck.
Li and Durbin themselves acknowledge that their technique cannot detect short sharp bottlenecks.
…simulations did, however, reveal a limitation of PSMC in recovering sudden changes in effective population size. For example, the instantaneous reduction from 12,000 to 1,200 at 100 kyr ago in the simulation was spread over several preceding tens of thousands of years in the PSMC reconstruction.
Buggs concludes:
Thus I cannot see that PSMC analyses (many more of which have been done on human genomes since the original paper by Li and Durbin) can be cited as rigorously disproving a short, sharp bottleneck.
Incomplete Lineage Sorting
Short and sweet: incomplete lineage sorting doesn’t matter because it all happened before the human lineage was established.
Venema makes an argument based on incomplete lineage sorting among humans, apes and gorillas, which gives a large estimated effective population size. This argument is not relevant if we are only interested in the human lineage (the occurrence of ILS does not require maintenance of large populations sizes in every lineage after speciation and so does not exclude a bottleneck in the exclusively human lineage).
Conclusion
None of the methods that Venema cites are able to address the problem of the existence of a first pair. Either they are insensitive to short sharp bottlenecks (reduction in genetic diversity, PMSC) or they are not designed to ask the questions at hand, and even engage in somewhat circular reasoning (linkage disequilibrium, incomplete lineage sorting), or they neglect the fact of explosive population growth and high rates of mutation accumulation (allelic richness). It is not to say that these papers are bad, rather they do not address the possibility of a short sharp bottleneck. For that a new approach is needed.
In closing it is best to let Buggs speak for himself:
The question asked by my religious friends is different to the questions being asked in the studies discussed above. My religious friends are not asking me if it is probable that humans have ever passed through a bottleneck of two; they are asking me if it is possible. None of the studies above set out to explicitly test the hypothesis that humans could have passed through a single-couple bottleneck. This is what we need to nail this issue down.
I would very much appreciate feedback from scientific readers of this blog. I have dealt with arguments made in a single book chapter, that has addressed this issue more directly than any other source I have come across. The author, Dennis Venema, is the go to expert on this issue within the organisation BioLogos, set up by Francis Collins (now director of NIH) to explore science-faith issues, so he ought to know what he is talking about. However, there may well be other, perhaps better, arguments that Venema has not made and I have therefore not interacted with.
If I am missing something, then I would very much like to know. Whilst this issue may seem trivial to many readers, for large numbers of religious believers in the world, this is a critical issue. Do they really face a binary choice between accepting mainstream science and believing that humans have, at some point in their history, all descended from a single couple? I am open to the possibility that they do face this dilemma, but I need more evidence before I am persuaded.
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