The 99.9% truism

There has been much comment on a recent finding that human evolution has accelerated over the past 40,000 years, i.e., the period during which our species has spread out of Africa and differentiated into the populations we see today (Hawks et al., 2007). There has been less comment on a related finding: at least 7% of the human genome has changed over the same 40,000 years.

This second finding seems to challenge a truism that has become widespread in academia and even in our political culture. In a speech earlier this year, Hillary Clinton cited genetic research showing that human populations are 99.9 percent the same and “that the differences in how we look -- in our skin color, our eye color, our height -- stem from just one-tenth of 1 percent of our genes.”

Isn’t there a contradiction here? How can human populations be 99.9% genetically identical if at least 7% of the genome has changed since they began moving apart some 40,000 years ago?

First, the 99.9% figure is not the number of genes that are the same. It’s the number of nucleotide sequences that are the same. A single gene is a long chain of nucleotides, often a very long one, and a single nucleotide mutation can significantly alter how the entire gene works. In theory, each and every human gene could differ by 0.1% from one population to another. And such a difference could make a big difference.

Second, the 99.9% estimate doesn’t capture higher-level nucleotide variation:

The technique originally used … could read the sequence of letters of a genetic code. But it couldn't detect repetitions of some parts of the code, which also occur. Differences in the number of these repetitions, called copy number variants, have since turned out to account for much of the variation in a species' DNA. Another type of variation recently found to be important is called insertion-deletion variants, snippets of code that are either extra or missing in some genomes compared to others. (World Science, 2007)

This higher-level variation has caused geneticist Craig Venter (of the Human Genome Project) to revise the 99.9% figure downward:

The find­ings re­veal “hu­man-to-hu­man varia­t­ion is more than sev­en-fold great­er than ear­li­er es­ti­mates, prov­ing that we are in fact very un­ique in­di­vid­u­als at the ge­net­ic lev­el,” Ven­ter said. The 99.9 fi­gure might need to be lowered to about 99, he added. (World Science, 2007) (also see original article: Redon et al, 2006)

So our nucleotide sequences may be closer to being 1% different, and not 0.1%. And don’t be fooled by small numbers. Whether it’s 1% or 0.1% the difference is still big in absolute terms. As John Hawks points out: “one-tenth of 1 percent of 3 billion is a heck of a large number -- 3 million nucleotide differences between two random genomes.”

Finally, there is a third reason why we should not read too much into any of these estimates. When the 99.9% figure first came out in the 1970s, geneticists had also discovered that nucleotide sequences were 98.9% the same between humans and chimpanzees (King & Wilson, 1975). And yet, humans and chimps exhibit a wide range of anatomical and behavioral differences. How come?

There is of course the aforementioned ‘small percentage fallacy’: a tiny sliver of the genome still amounts to a lot of DNA. More importantly, humans and chimps seem to differ the most in ‘regulatory genes’ whose effects are many times greater than those of ‘structural genes’ (the ones that code for the building block proteins of body tissues). A single regulatory gene has such a disproportionate impact because it can control the expression of many other genes.

These less numerous regulatory genes have gained importance as organisms have grown more and more complex. This has especially been so during human evolution. Whereas humans and chimpanzees are almost identical in the proteins that form their tissues, they differ radically in the way their brains and bodies develop. This point is summarized by King and Wilson (1975, p. 115):

The genetic distance between humans and chimpanzees, based on electrophoretic comparison of proteins encoded by 44 loci is very small, corresponding to the genetic distance between sibling species of fruit flies or mammals. Results obtained with other biochemical methods are consistent with this conclusion. However, the substantial anatomical and behavioral differences between humans and chimpanzees have led to their classification in separate families. … A relatively small number of genetic changes in systems controlling the expression of genes may account for the major organismal differences between humans and chimpanzees.

Interestingly, King and Wilson see this paradox as applying not only to human-chimpanzee genetic differences, but also to genetic differences within our species:

This [human-chimpanzee] distance is 25 to 60 times greater than the genetic distance between human races. In fact, the genetic distance between Caucasian, Black African, and Japanese populations is less than or equal to that between morphologically and behaviorally identical populations of other species. (King & Wilson, 1975, p. 113)

Yet human races are not identical populations, anymore than humans and chimpanzees are sibling species. These measures of genetic distance are not comparable because the nature of genetic change can vary dramatically. In one case, there is simply tinkering with an existing body plan through mutations in structural genes. In another, there is radical developmental change through mutations in regulatory genes.

Since the time that the ancestor of these two species lived, the chimpanzee lineage has evolved slowly relatively to the human lineage, in terms of anatomy and adaptive strategy. According to Simpson:

Pan is the terminus of a conservative lineage, retaining in a general way an anatomical and adaptive facies common to all recent hominoids except Homo. Homo is both anatomically and adaptively the most radically distinctive of all hominoids, divergent to a degree considered familial by all primatologists. (King & Wilson, 1975, p. 113)

This is the context in which the 99.9% statistic was initially presented to the academic community … way back in the 1970s. Even then, researchers thought it misleading and went to great pains to explain why it was misleading. Yet their caveats were to no avail. The 99.9% truism has taken on a life of its own, much like those stories we hear of alligators living in sewers or evil people sticking razor blades in Halloween apples. It seems to meet a deep-seated need to affirm our sameness and to give this affirmation a stamp of scientific approval.

But science it is not.

References

Anon. (2007). Finding said to show "race isn't real" scrapped http://www.world-science.net/othernews/070904_human-variation.htm

Elliott, P. (2007). Clinton tells grads only minor genetics make them different.
http://www.boston.com/news/nation/articles/2007/06/14/clinton_tells_grads_only_minor_genetics_make_them_different/

Hawks, J. (2007) Disagreeing with Hillary Clinton on human genetic differences.
http://johnhawks.net/weblog/topics/race/differences/clinton_2007_proportion_differences_speech.html

Hawks, J., E.T. Wang, G.M. Cochran, H.C. Harpending, and R.K. Moyzis. (2007). Recent acceleration of human adaptive evolution. Proceedings of the National Academy of Sciences (USA) early view.

King, M-C. and A.C. Wilson. (1975). Evolution at two levels in humans and chimpanzees. Science, 188, 107-116.

Redon, R., S. Ishikawa, K.R. Fitch, L. Feuk, G.H. Perry, T.D. Andrews, H. Fiegler, M.H. Shapero, A.R. Carson, W. Chen, E.K. Cho, S. Dallaire, J.L. Freeman, J.R. González, M. Gratacòs, J. Huang, D. Kalaitzopoulos, D. Komura, J.R. MacDonald, C.R. Marshall, R. Mei, L. Montgomery, K. Nishimura, K. Okamura, F. Shen, M.J. Somerville, J. Tchinda, A. Valsesia, C. Woodwark, F. Yang, J. Zhang, T. Zerjal, J. Zhang, L. Armengol, D.F. Conrad, X. Estivill, C. Tyler-Smith, N.P. Carter, H. Aburatani, C. Lee, K.W. Jones, S.W. Scherer & M.E. Hurles. (2006). Global variation in copy number in the human genome. Nature, 444, 444-454.