The Origin of the Future: Death by Mutation?

By Carl Zimmer | January 7, 2010 1:08 am

Last month I wrote an essay about the future of evolution for Science. I paid particularly close attention to what will happen to our own species, describing some recent research and ideas from scientists. Natural selection will not stop, nor will the emergence of new, neutral mutations.

But this week, the evolutionary biologist Michael Lynch has published a provocative paper (to mark his inauguration into the National Academy of Sciences) in which he makes another kind of forecast. Our future evolution, he warns, is going to lead to a devastating decline in our health.

The idea is not new. Hermann Muller, who won the Nobel Prize for his work on mutations, first raised the specter of evolutionary decline in 1950. He pointed out that many mutations that arise in a population are harmful. They can cause various diseases, cutting lives short or making it harder for organisms to reproduce. Left to themselves, these mutations can drive down the reproductive rate of a population. But their harmful effects can be balanced by natural selection. If individuals with harmful mutations have fewer offspring than other individuals, the mutations become less common. Overall, the population can continue to reproduce at a healthy rate.

As Lynch points out, Muller’s argument depended on the actual rate of mutations and other vital statistics that no one in the 1950s could know with much precision. But in his new paper, Lynch surveys recent studies that make it possible to know the mutation rate quite well. Lynch concludes that every gamete (a sperm or egg) acquires the following:

–38 base-substitution mutations (a single “letter” of DNA changes to another one).

–3 small insertions or deletions of a stretch of DNA

–1 splicing mutation (which changes the combination of segments of a gene that cells use to build proteins)

–Plus some assorted other mutations (gene duplications, insertions of DNA copied by transposable elements, and so on).

All told, Lynch estimates a total of 50 to 100 mutations.

Compared to other species, Lynch points out, we mutate a lot. Any base in our DNA is twice as likely to mutate as a base in a fruit fly’s DNA, for example. Part of our special burden is our long life. As sperm divide rapidly during a man’s life, they pick up lots of new mutations. We are also left prone to cancer, as our skin, intestines, and other tissues continue to divide and sometimes pick up new mutations.

A lot of the new mutations in every new baby are harmless. But each baby may acquire a few harmful ones. These mutations rarely cause a swift death. Instead, in their totality, they slice off a tiny fraction of the total offspring an entire population can produce. Lynch estimates that mutations to protein-coding DNA cause the fitness of a population to decline by 1%. That’s assuming natural selection does not favor other mutations over these harmful ones.

Lynch acknowledges that natural selection is still in effect in humans, particularly in places where people never see doctors, let alone get clean drinking water. But as the world’s standard of living goes up, he argues, more and more people are being shielded from natural selection’s most intense effects–and harmful mutations are piling up.

In a matter of a few centuries, Lynch predicts, industrialized societies may experience a huge increase in harmful genes–“with significant incapacitation at the morphological, physiological, and neurobiological levels,” he writes.

Battling this decline won’t be easy, says Lynch. Rather than a few big mutations causing the trouble, the decline will be brought about by a vast number of mutations, each with a very small effect. The fantasies of selective breeding dreamed of by eugenicists aren’t just loathesome–they’re also useless. Instead, Lynch argues for something that would make the eugenicists crazy. “Ironically, the genetic future of mankind may reside predominantly in the gene pools of the least industrialized segments of society,” he writes.

Image: IU


Comments (18)

  1. Sterling K. Webb

    As usual, journalism is illiterate, or in this case,
    innumerate. “Lynch estimates that mutations to
    protein-coding DNA cause the fitness of a population
    to decline by 1%.”

    1% per minute? 1% per hour? 1% per day? 1% per
    year? 1% per decade? 1% per generation? Presumably
    Mr. Lynch knows what he’s talking about. But we have
    no way to know, thanks to journalism!

    I will assume that he means “per generation” since that
    is the natural cycle of a population’s gene expression.
    Hmmm… Since life began 4,000,000,000 years ago, there
    have been, oh, 3,000,000,000 generations, as all creatures
    now alive have ancestors all the way back (by definition).

    Therefore, all life is now 30,000,000 times LESS FIT than
    when it began. It’s a blanking miracle anyone is still alive!
    Perhaps I should only count generations since the Cambrian?
    Then life would only be 3,000,000 times less fit… However
    you calculate it, life should have gone quite extinct long, long
    ago. Mathematical models of reality are wonderful things,
    except of course when they are utterly mad. Math is only
    “true” within arbitrarily narrow and very limited conditions,
    and life is rarely like that for very long.

    OK, the narrow view. The population of the US, 300
    million people with a “generation” of 25 years, will decline
    in fitness 1% in 25 years. Partial or distributed genetic
    death is equal to the defect rate. That amounts to the
    equivalent of a death rate of 120,000 persons per year.
    That’s a lot of people, but hardly equal to the more than
    500,000 cancer deaths per year.

    Hey! Wait a minute! Maybe many of those cancer deaths
    are some of the 120,000 deaths due to “mutations to protein-
    coding DNA”! Or, maybe, some of those “mutations to
    protein-coding DNA” are the ones that make me smoke
    and become more liable to premature death? I feel less fit

    I come from hale and hearty stock, millennia ago. By now,
    presumably, the on-going 1% decline in the “fitness of a
    population” that began 100 generations ago (2500 years)
    would by now have brought me, their feeble descendent, to
    the level of zero fitness. The “level of zero fitness” would translate
    as “take a deep breath and drop dead,” I imagine

    2500 years ago my ancestors were wearing scratchy homespun
    rags, shivering in a drafty hut, eating nuts and berries and the
    occasional unwary hedgehog barbequed over a smoky peat fire.
    They had to be fit. And my need for canned hedgehog soup, my
    dependence on my microwave and some well insulated walls
    and the gas furnace are all signs of my extreme and terminal
    degeneration. Is this the “level of zero fitness”? I would like to think
    that I could still take my hedgehog roasted on a twig, if necessary…
    So perhaps I am not “zero” fit.

    The true flaw here is the notion that anyone, whether in an industrialized
    society or not, is “shielded” from natural selection, which acts equally
    on all members of a population regardless of their opinion of their own
    status. The errors here are beyond counting.

    This is: Garbage. Bilge. Tripe. Manure. Can I say it any more plainly?

    “A wise man will enjoy the goods of which there is a plentiful
    supply, and of intellectual rubbish he will find an abundant
    diet, in our own age as in every other.” — Bertrand Russell

    CZ: Sterling–Before you analyze Lynch’s argument (or insult my ability as a journalist), please get familiar with the concept and measurement of fitness. I’ve also taken the liberty of emailing you Lynch’s paper to peruse.

  2. “In a matter of a few centuries, Lynch predicts, industrialized societies may experience a huge increase in harmful genes”

    Assuming this is correct….Isn’t it completely academic?

    How long before we can treat any genome like a word document, cutting and pasting efficiently with little effort. Granted, such changes should never be made arbitrarily but one of the first no-brainer applications of such a technology would likely be to prevent or fix new mutations.

    CZ: Bob–The genome is a lot more complicated than a word document. For one thing, mutations interact with each other in weird ways. Also, there are a vast number of mutations that contribute to the decline of fitness Lynch is arguing for. So it’s not a given that scientists could easily engineer a way out of this.

  3. This really makes sense to me. We’re living a lot longer overall and reproducing a lot later in life. More of us are surviving to reproduce. Near-sightedness that might have gotten you eaten a few thousand years ago is corrected with glasses and any genetic causes of it are passed on. And there are so more synthetic and novel mutagens in our environment.

    Unrelated but in the news today: 8% of human DNA came from viruses.

  4. DavidB

    Natural selection operates through differential fertility as well as mortality. If those who have more than an average number of harmful mutations have fewer offspring, the decline in fitness would be offset. People also sometimes forget that natural selection operates from conception onwards, and the majority (probably) of all fertilised eggs are spontaneously aborted, sometimes for genetic reasons. I don’t know whether the author has taken these factors into account, but if he has not, his conclusions are invalid.

  5. I’m with Oroboros. In the developed world we save a great many lives that would have been lost in primitive cultures. This might be a cultural benefit (or not). But combine it with our long reproductive life, and who knows where it will lead? I’ve always wondered about this evolutionary aspect of human life. Thanks for publicizing this paper. And I loved your (totally appropriate) responsse to Sterling Webb!!!

  6. Stiffler

    Why cant our genes know that we dont want to change anymore. We’re very content with what they’ve achieved till now, I mean they gave us sexual reproduction and all. we seem to be pretty fit to survive and doing not too bad. why cant mutations stop for a while let us enjoy this moment and then maybe after climate change start shuffling up again. Why does it evolution have to spoil this temporary bliss for such a wonderful intelligent species?

  7. katesisco

    Just finished Aquagenisis and was wowed. Really demonstrates the 99.9% of all species go extinct. The longest livers: from the world of 200 million years ago: crocs, coelecanths, crabs (horseshoe) and cockroaches. I think mammals fit together there as bats are essentially unchanged as are an amazing number of other animals from 30 mya, when the Chesapeake Bay meteor (2m diam) slammed the eastern NA coast, annihilating all life over to the Mississippi. Megafauna that ate the Osage Orange disappeared.
    I would agree that mutations are the future but that the ‘trigger’ has to occur first, otherwise the hammerhead shark would not be here. Imagine a creature that carries its eyes on slabs of flesh hanging a foot from its face (jaws). How could it live unless it was big enough to not be prey for others. Consider the world of the Florida manatee; as vividly described in the NA anthology of nature writing (W Bartram), where alligators mass in such numbers that “one could walk across the river on their backs”, how could the manatee survive in such a world? It couldn’t. The reason it did is that the crocs amassed to eat the flood of fish that arrived with the daily current. The crocs ate the fish and had no need for manatees. We arrived, killed the crocs, then ate the fish and discovered the manatee while it still lived. Everything is balance. A compter command: If not, then>
    Almost makes me believe in Gaia.
    Every extinction event produces a new rearrangement of dna, some of which survive in spite of its seeming unsuitability.
    Over 3500 years ago the people of Harappa lived in sewered apartment houses and survived by trade/commerce. They were cloth dyers. There is ample evidence that such occurred many times.
    I particularly am fond of the aquatic ape theory. In so far as the author posits that hairlessness occurred only in underground animals or water animals. Suppose we combine the two, as the blue penguins do in Australia. These 17 inch high animals live in land burrows by day and fish (rafted together) by night. Is that not amazing or what? And she conceded that penguins are the only other upright walker on two feet!! I just believe that she failed to include our “time in the dark.” Cro-Magnon is supposed to have left beautiful art deep inside caves, why and how? What if the mutation for hairlessness happened first and there were sufficient numbers to create their own tribe. Consider Ashy, a hairless chimp, a social outcast which would not survive in the wild but does in the zoo where he lives. The outcasts (hairless in a hairy group) would have had to live somehow, away from those who would kill the mutations. Sounds like resorting to the depths of a cave to me.
    And consider that vitiliago, the auto immune reaction that creates white spots on the body of humans. Not so different from the pinto coloration in horses which is conceded to be a trait implicit in tameness. But, in humans, much feared as the affected are labeled as different, outsiders, not-like-us. How did humans acquire their defect that leads to vitiliago? Was it a mutation that incidently was much more common in ancient Egypt and India than now? says we are experiencing the greatest exposure to cosmic rays since such have been measured. And as for our society, please not mustard gas (nitrogen mustard0 is a dna mutagen, the first of a long line which we seem determined to continue.
    Are we going to mutate, you bet. Are we mutating now, you bet. Check your mdna.

  8. Jan-Maarten

    “Ironically, the genetic future of mankind may reside predominantly in the gene pools of the least industrialized segments of society”

    Sounds familiar, kind of; old, inbreeding dynasties being overthrown by healthy young warlords!

  9. LGSmith

    “Ironically, the genetic future of mankind may reside predominantly in the gene pools of the least industrialized segments of society”
    Rather like Bernard Kettlewell’s Industrial Melanism in reverse. It seems reasonable that incremental changes will continue in all biological organisms. It’s all so elementary, my dear Watsons!

  10. Daniel Lawson

    There is an additional force at work that can offset the accumulation of deleterious mutations: sexual selection. Our concept of beauty is pretty much in line with healthiness, and its well known that people partner at their own rough level of attractiveness. This will maintain a high level of healthiness in some individuals, even though the average fitness will still decline of course. There will be gene flow between individuals of different genetic health so a diversity of numerous unhealthy individuals will still be able to contribute to the long-term human gene-pool.

    So although the natural healthiness of the population will decline, this is not a loss in fitness (because these mutations can be offset by medicine, or they can’t spread) and the “naturally fit” individuals will still exist due to sexual selection for these traits. There will be a mutation-selection balance that, yes, will result in many unhealthy individuals kept alive by health care facilities, but some people will still be “as fit” as those evolved in harsh environments, particularly as the same health care facilities allow a larger population to be maintained (therefore a smaller proportion of people need to be fit in order to maintain the same numbers of fit individuals).

    Coupled with the above arguments that people with health problems may naturally have less offspring, and the possibility for genetic engineering, this is not strong evidence that we should worry. At the very least, we need a demographic model that takes into account non-random mating and population sizes to demonstrate that healthy haplotypes will be lost from our population.

    (The research is still very interesting, but any conclusions about humanities future are premature. Of course, we can clearly see that people in developing nations are “more fit” in terms of surviving offspring than those in industrial nations at the moment due to social pressure on birth rates. But such social structure has little/no genetic basis.)

  11. Brian Too

    This is a case of selectively finding the bad in a story that’s fundamentally good.

    More people are surviving and living better lives than ever before. That’s bad news??

    Back to basics time. Mutations are a key driver of evolution. We’ve got this far on the system and a few new kinks (i.e. effective medical care) do not fundamentally change the dynamic. They do not.

    As of right now we have genetic counselling for major problems in the prospective parents. Couples can choose to alter their reproductive choices. We also have genetic testing (and other testing) on the fetus. Soon we’ll have effective genetic interventions for anyone with serious genetic problems, including their germ cells.

    Eventually we’ll have full control of our DNA and the problem won’t be “accumulating small genetic errors over centuries”. The problem will be what do we do with all that power. The problem will be using genetic control to address vanity and trivia. The problem will be do we start a directed evolution to become another species, or an explosion of many new species. The problem will be do we continue to understand one another and share values and goals if this happens.

    This is really a non-issue as presented.

  12. It certainly is an issue, and one that should be studied.

    That’s not to say we’re ready, ethically or scientifically, to deal with it on more than a case-by-case medical basis.

  13. ajuc

    Isn’t it obvious, that evolution is working at all times, and humans are evolving to be more dependant on the technology (for example medicine).

    BTW – my answer to make life span of people longer – find a way to allow reproduction of people thoroght their whole life – that way evolution will ensure we will be more healthy and, one after another, things that kills people at older age would be resolved by sheer power of natural selection.

  14. Jim Thomerson

    There was a letter in Nature, maybe 15 – 20 years ago which stated that families with a history of cystic fibrosis had a 50% higher rate of reproduction than similar families with no history of cystic fibrosis. This was taking into account the deaths from cystic fibrosis. As I recall, the 50% increase was all male.

    If we compare the growth rates of two populations, doesn’t the one with the faster growth rate have higher average fitness? It is not the most technologically advanced populations which exhibit the highest population growth rates. Selection is more intense in Japan, for example, than it is in the Arab countries.

  15. Frank Rossi

    Kate- I’m assuming (in a good way) you’ve read Galapagos.

    I am of Southern Italian descent, and love it when I hear racist remarks from my fellow swarthy mediteraneans in regards to Africans. It’s like Art Mooney said, “nobody hates like family.

    It seems that we will not run low on unfortunate people ironically aiding our race as they suffer into each new generation. Wars over our depleted natural resources are already being waged. As our fresh water runs out, there will be even more “natural selection”.

    As for those wacky eugenecists, I hope men like Henry Ford are rolling in their graves as they burn in hell.

  16. Quercus

    I’m very confused by this argument, at least as explained by this blog. How can a mutation be ‘harmful’ but not affect reproductive fitness? Does the author somehow not understand that a mutation can reduce reproductive fitness in one environment (say, stone-age hunter gatherer society), but not in another (modern technological society), and therefore what’s ‘harmful’ depends on the environment?

    The argument seems to be: there are many mutations that would be negative-fitness in a pre-technological society. In our current society, technology can compensate for some of those mutations. Therefore, the human gene pool is going to accumulate these mutations, dooming the species to, uh, having an esthetically yucky gene pool or something. OK, at worst, if technological society survives long enough to fix technologically-compensatable mutations, it dooms large fractions of humanity to being reliant on technology. Given the ‘if’, is the result really something to be alarmed about?

    Again, maybe I’m missing a key part of the argument, but it seems like this is a pseudo-scientific version of “Society is going downhill because we’re coddling our kids too much with the doctors and sanitation, not like when I was a kid and we had to walk 53 miles uphill both ways through the snow just to get to school!”.

  17. Rork

    The number of relatively new mutations in the population may already have increased since the old days just cause Dad’s average age at conceiving has increased, so if the old-timer’s want kids, fight back and use sperm frozen at puberty. (I used to argue that with a certain physician to the gene pool, who wanted us to be older when having kids, mostly to reduce population growth.) An alternative is to change society – have kids young but you only get to actually raise your grandchildren, not your genetic children.


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The Loom

A blog about life, past and future. Written by DISCOVER contributing editor and columnist Carl Zimmer.

About Carl Zimmer

Carl Zimmer writes about science regularly for The New York Times and magazines such as DISCOVER, which also hosts his blog, The LoomHe is the author of 12 books, the most recent of which is Science Ink: Tattoos of the Science Obsessed.


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