Sex, Errors, And The Genome

Can human beings keep evolving? Or does the error-ridden process of reproduction prevent us from getting more complex than we already are?

When extraterrestrial visitors land on Earth in their space saucer, they will be excited to see that ours is one of those rare planets on which complex life has evolved. They will already have found microbes--organisms resembling our viruses and bacteria--on every other life-bearing planet. And they will know that the real fun begins not in trying to understand how life on Earth came to exist at all but in how such complex forms as humans and butterflies and clams and whales and trees came about. And a question they will certainly ask is, How many copying mistakes does earthly life make when it reproduces the hereditary molecules of its DNA code?

When we (and other life-forms) produce offspring, our genome--the sum of all our individual DNA--is copied. But the repeated copying that takes place prior to pregnancy, during numerous divisions of our reproductive cells, can alter the messages in our genome--much as the children's game of Chinese Whispers (called Telephone or Gossip in the United States) distorts a verbal message as it is repeated from one person to the next. By the end of the line in Chinese Whispers, the message is laughably corrupted.

Through 3.5 billion years of evolution, life-forms have been able to perpetuate themselves--and become more complex than their ancestors--partly because they evolved ways of dealing with these copying errors. Double-stranded DNA (which appeared quite early in the history of life) and certain enzymes work within the cell nucleus to prevent errors from happening in the first place. Other enzymes correct most of the errors that nonetheless arise: proofreading and repair enzymes correct errors in the code, and developmental troubleshooting enzymes correct the expression of a faulty code without correcting the code itself. But the most important factor in the evolution of complex forms, which contain many genes (and therefore the possibility of making many errors), was the evolution of sex. Because sex takes one set of genes from each parent and recombines them, it shuffles the errors that manage to slip through all the defenses and improves the odds that at least some healthy, error-free offspring will result. This crucial innovation probably arose about 2 billion years ago, around the time that a more complex cell type--called the eukaryotic cell--originated.

Nonetheless, human beings are quite error prone. When we copy our DNA, we make more mistakes than most, if not all, other forms of life on Earth. In fact, every human being is conceived in 200-fold copying error. How many of these 200 mutations are harmful is not known. Most errors seem to be neutral, and a very few may actually help the organism, but even rigorous accounting cannot squeeze the harmful-error rate to below about 2 per conception. A figure of 5 to 10, or even 20, harmful mutations per conception may be quite likely. These high numbers are a consequence of our complexity. A human being contains 30,000 genes, included within a total of some 6.6 billion or more units of DNA. A bacterium might have on the order of 2,000 genes and 2 million units of DNA. The unit error rate, however, is similar in humans and bacteria. Humans therefore make more mistakes than bacteria do, for much the same reason that a scribe is more likely to make mistakes when copying the Bible--a job that took about a year and a half in the Middle Ages--than when copying a single psalm.

Another, and perhaps even more important, reason we humans are error prone is that we are long lived, with an average of thirty years between one generation and the next. Mutation rates are higher in long-lived animals such as humans because we copy our reproductive DNA a number of times in the interval between when we ourselves are conceived and when we beget our own children. (See "Mutations: Mother Versus Father," above.) And--complicating matters further--not only do most human embryos contain about 200 copying errors, or "typos," in individual DNA messages, but about 50 percent of these conceptions have a botched number of chromosomes. The length of a typical generation is probably a factor here, too, because the percentage of such errors in rabbits or guinea pigs--with generations measured in weeks or months--is negligible. Even if half of all embryos have chromosomal errors, that still leaves 50 percent that are potentially available to carry the human species forward. And these will of course have, on average, 2 to 20 damaging typos.

Any individual may produce some faulty young, but for humans or any sexually reproducing form of life to persist, the average parent must produce at least one error-free offspring. Luckily, in addition to having enzymes that prevent or correct copying errors, we also have sex, which provides each offspring with a helpful redundancy of genes. In fact, our cells contain four copies of the information for each genetic instruction--a paternal and a maternal double helix. A correct version in one set will usually override a copying mistake in the other, so the average parent has a reasonable chance of producing a baby that will itself survive to reproduce. Unfortunately, sexual reproduction does not always prevent an embryo from picking up a whole extra chromosome or two. In this case, natural selection comes into play after conception: embryos with the wrong number of chromosomes almost always die in the very earliest stages of their intrauterine existence. (Those who have extra chromosomes but do survive, such as people with Down syndrome, often have significant health problems.)