On the effects of effective population

By Razib Khan | July 24, 2012 11:23 am

Nathaniel Pearson has an eminently readable post up on human effective population sizes. If you don’t know the importance of harmonic means in this domain, worth a read. He finishes though with an issue of practical importance, the proliferation of individually deleterious alleles at the large census sizes we see us today:

Along the way, our changing population size may shape public health in complex ways. In particular, a key question will be what happens to the likely sizable subset of newly arisen rare variants that pose health risks to people who carry them. As our population continues to skyrocket, more such variants will come into our midst.

At the same time, continued population growth should ultimately help natural selection purge such variants more efficiently than it can in a small population (where chance dominates the fate of variants, harmful or not).

But, to the extent that our future population growth itself depends on further advances in healthcare, we’ll also be altering the regime of such natural selection, ideally relaxing it in ways that help people live healthier lives no matter what variants they carry in their genomes.

As Mark Ridley observed in The Cooperative Gene natural operates in utero as well. Even assuming that natural selection is not purging deleterious alleles with great efficiency today, high human miscarriage rates are going to serve as a counterbalance to better healthcare for the genetically less fit.*

* On the order of ~50% of pregnancies miscarry, with the majority being cryptic, as women may not have known that fertilization occurred due to failure of implantation or problems in the first month).

CATEGORIZED UNDER: Genetics, Genomics
  • AG

    The entire reproductive process is natural selection from the beginning. Mate selection, individual sperm quality, miscarriage, infant mortality are all part of purge of dleterious alles. Darwin natural selection at every step for healthy genes.

    Modern medicine and morality are anti-natural in some degreee.

    But large population size always has edge over small one.

  • https://plus.google.com/109962494182694679780/posts Razib Khan

    i’d remove the modifier ‘natural.’ selection is just selection. there is still reproductive variation, and if it’s correlated with genetic variation, then selection is still operative.

  • gcochran

    Let us suppose that the effective population size used to be 10,000, so that deleterious variants that decreased fitness by less than 1 part in 10,000 (0.01%) were ineffectively selected against. During the Holocene, populations grew a lot, so that selection is potentially more effective. How long would it take for this more-effective selection to materially reduce the number of such slightly-deleterious alleles?

    10,000 generations. A quarter of a million years. I can hardly wait!

  • AG

    meiosis process with homologous recombination would help a lot here. That means an individual with deleterious alleles still can produce total perfect gametes. Male produces more gametes due large number of sperm production and contributes more than female.

  • AG

    Love this kind of debate and it helps to figure out meaning of many biological process. Discovery is always standing on other’s shoulder.

  • AG

    This bebate also illustrates the significance of meiosis/sexual reproduction as important biological means to keep mutational load down more efficient than simple mitotic cloning/asexual reproduction with huge population like bacteria.

    Also this indicates cloning as way of reproduction with inherited weakness.

  • AG

    “10,000 generations. A quarter of a million years. I can hardly wait!”

    For bacteria, it is quite possible since its life cycle is quite fast and short. No need for thousands years wait.

  • Chad

    As a practical matter, it is unlikely that healthcare will ever (at least anytime soon) those stages where pregnancy is undetected, as you rightly point out. However, the care of prematurely born children along with increasing abilities to treat in utero is pushing the “anti-selection” effects of healthcare deeper into the womb.

    One can also envision not just healthcare, but culture and society acting against this a la Idiocracy. Where people of lower intelligence or undesirable behavior traits reproduce at higher rates. Of course this requires the view that lower intelligence or certain behaviors are deleterious. I hesitate to say stuff like that because it always seems to imply a certain sense of teleology to Evolution. When in reality if they lead to greater reproduction in the culture we have established, then Selection is following its course, even if it seems rather artificial since it is culture/society, not “nature” driving the changes.

  • http://dispatchesfromturtleisland.blogspot.com ohwilleke

    * Re New High Estimates Of Modern Human Effective Population Sizes

    The linked post notes new estimates of effective human population sizes for both all humans and for Eurasia on the order of 500,000-1,000,000, as opposed to more traditional estimates on the order of 5,000 to 10,000 (a factor of one hundred smaller) determined with more greatly simplified assumptions.

    It is quite hard to imagine historically sensible early modern human migration scenarios in which the larger values could have happened in the relevant Paleolithic eras. Indeed, what we know about the geographic range of early modern humans in those areas and the population densities typically associated with the hunter-gatherer lifestyles in various ecologies within those geographic ranges, also casts real doubt on the larger effective human population size estimates.

    While those numbers are all back of napkin themselves, migrations involving 500,000-1,000,000 people in the effective population (and generally, a larger actual census population) are hard to square with that analysis. This is on the scale of some of the largest 19th and 20th century mass migrations but with far inferior means of transportation and far less carrying capacity of the destination for a given land area.

    At some point, all non-Africans have ancestors who were predominantly modern humans who left Africa via either the Sinai or Gate of Tears (i.e. at one or the other end of the Red Sea), before going further. While the Out of Africa era was surely a more fertile one in this region than it is now, this first of the Out of Africa serial bottleneck regions could never have supported all that many people living in a hunter-gatherer mode with stone age technology even in eras when its climate was most agreeable. And, it seems likely that the migrating population that eventually would have expanded to reach peak carrying capacity in this range would surely have been smaller than peak carrying capacity at the time of migration. So, the effective population size of Eurasia, intuitively, ought to be meaningfully smaller than the peak carrying capacity of the Near East in its most fertile era for Paleolithic hunter-gatherers. One can also very plausibly imagine this non-African founding population experiencing at least one bottleneck before it expands further for example, when climate first takes a turn for the worse post-migration.

    The way you calculate effective population size means that there is no necessary relationship between the census population of a migrating people and this Platonic ideal calculation, but population geneticists and anthropologists like to think about effective population size precisely because it tends to track minimum population size over the population’s history (since it is based on a harmonic mean) and because historically minimum population size is generally going to match founding population size when modern humans enter virgin territory.

    So we should take pause when a methodology comes up with an estimate for effective population size that is much larger than a reasonably plausible founding population size for modern humans entering virgin territory.

    The great divergence in estimates using seemingly similar methodologies and similar core empirical inputs also seems to suggest that something is rotten in Denmark.

    * Re Purifying Genetic Drift After Considering Population Growth Rates

    The linked post also has a very powerful visual representation of the tendency of a population of stable size with considerable genetic diversity to converge to a most recent common ancestor due to pure random genetic drift alone. But, the story that this image tells is probably too strong and leads to the wrong intuition about the power of genetic drift in non-stable populations which are historically more common.

    It doesn’t take all that much population growth to dramatically reduce the amount of lineage pruning due to random genetic drift and even modest population shrinkage can greatly boost lineage pruning due to random genetic drift before even considering selective effects related to the cause of the shrinkage. The assumption of a stable population in the baseline scenario turns out to be a fragile and sensitive point of unstable equilibrium that usually isn’t very realistic for most of the intesting parts of modern human demographic history.

    Somewhat more subtle demographic models would observe that you’d expect populations of modern humans entering virgin territory to have s-shaped logistic curve patterns of population growth – slow growth at first due to the limits imposed by small founding population sizes, followed by rapid growth as a percentage of carrying capacity, followed by slowing growth again as the population approaches carrying capacity – as each new territory is opened up, rather than uniform rates of population growth.

    A logistic curve pattern of population growth should lock into the initial near carrying capacity population almost all of the genetic diversity that was present prior to the growth phase when the effective population was much smaller, and should then very gradually (since the carrying capacity population is so much larger and there are so many copies of all of the founding population variants that survived to participate in the growth phase) wean out some of that diversity over time via random genetic drift. The new, much larger population should start out with something close to a fixation level of genetic diversity that has all of the components of the pre-growth phase population in proportions tweaked by exaggerated random chance variations that arise during the growth phase.

    A logistic curve growth model should also greatly influence the relative importance of mutations in the early slow growth, middle rapid growth, and late slow growth phases of the process.

    Purifying random genetic drift should be concentrated in the early slow growth phase of the logistic curve, when total population sizes are much smaller since the total population then stays small relative to peak carrying capacity population for a long time in a way that is a rough approximation of a small stable population that stays that way for a long time before taking off and growing.

    Mutations in the final population should mostly derive from mutations taking place in the early and late phases, not in the rapid growth phase where the small number of generations involved relative to the time frame of the entire process, and non-peak population sizes should limit the amount of mutation taking place in that phase.

  • http://lyingeyes.blogspot.com ziel

    “For bacteria, it is quite possible since its life cycle is quite fast and short. No need for thousands years wait.”

    Isn’t this topic about human populations?

  • AG

    Yes, if human reproduced without meiosis, it would have been like 10,000 generations for a quarter of a million years like Dr. Cochran calculated. But with meiosis, the calculation would not fit.

    But Dr.Cochran calcultation would be ok for bacteria since they reproduce through mitosis.

  • gcochran

    AG, you have no idea what you are talking about. What I said was correct.

  • http://julianodea.blogspot.com/ Julian O’Dea
  • jb

    I may be missing something, but I don’t understand your focus on on miscarriage as a brake on increasing mutational load. (You’ve brought it up before).

    My concern is that as a result of modern healthcare there could be a steady increase in mutational load in the general population, and a corresponding degradation in desirable qualities such as intelligence and robustness, maybe even to the point where a significant portion of the population might require constant medical assistance simply to maintain a decent day-to-day quality of life.

    So are we headed towards a future full of marching morons? What I’d really like to know is whether the problem is real, and if so how quickly it will become important, and how big the impact will be. It’s of course true that there will always continue to be selection through miscarriages. But all this will do is weed out those individuals who are so unfit that they can’t even survive to term (even with uterine intervention). It seems to me that the “floor” this provides will probably be well below the level of general unfitness I am worried about, so it doesn’t really help much. Am I wrong to think this?

    To get a rough measure of the problem, it seems to me we could ask what percentage of the population in the past (let’s say 200 years ago) failed to reproduce because they were unfit due to mutational load (as opposed being perfectly fit victims of war, plague, famine, etc.), and what percent of that group is reproducing today because of modern healthcare. I have no idea what those numbers are, and no idea where to look, but I’m nervous about what the values might be, and I would think it would matter a lot if we are talking about .2%, 2%, or 20%. Do you have any sense of what the numbers are? Or am I just entirely on the wrong track?

  • AG

    Your calculation is fine. It is original model problematic (due to many variables including meiosis).

  • AG

    @Julian O’Dea

    Brilliant work. I can not believe I came to the same conclusion like yours just yesterday. Your idea deserves more recogniction.

  • gcochran

    AG, you are mistaken .

  • AG

    @Julian O’Dea

    I gonna starting research project based on meiosis theory. I have some raw research materials and regional research institute to collaborate. If you are interested, you can be part of it since you came up with original idea. I can not find your email address on your website. So I have to leave my note here. Hope you can read this.

  • http://julianodea.blogspot.com.au/ Julian O

    AG, my email is as follows:


    Please mark any email clearly in the subject line as my home computer gets a lot of emails.

    I am not sure what you have in mind, but I am happy to discuss. I am semi-retired and I work from home. I have no university affiliation these days.


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About Razib Khan

I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. In relation to nationality I'm a American Northwesterner, in politics I'm a reactionary, and as for religion I have none (I'm an atheist). If you want to know more, see the links at http://www.razib.com


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