By Amanda Fox
November 15, 2002 | A new study challenges 30-year-old evolutionary biology dogma that humans and chimpanzees share 98.5 percent of their genetic structures, contending that the similarity between the two species is in fact only 95 percent.
The study, conducted by Roy J. Britten at the California Institute of Technology and published last month in the Proceedings of the National Academy of Sciences, found a 3.9 percent divergence between chimps and humans due to the presence of “indels” -- tiny insertions or deletions in the gene sequence. That’s in addition to a difference of 1.4 percent from single-nucleotide substitutions in the gene sequence documented in previous studies.
Britten assessed the level of divergence between five chimpanzee sequences downloaded from GenBank and matching regions of the human genomic sequence -- 780,000 bases total -- using a Unix box and three main programs: BLAST, to determine areas of alignment; RepeatMasker, to “mask” the human repetitive sequences; and a novel Fortran program that moves sequentially along the synchronized pair of sequences to ascertain whether a mismatch is a base substitution or an indel.
“When I went after checking the divergence results, I didn’t have any idea that the deletions would be important,” says Britten. “In fact, [indels are] the most interesting part of the whole story.”
Factoring in indels doesn’t change the relationship between chimpanzees and humans, says Britten. “It’s just background information to help you understand the evolution. The real issue of human and chimp evolution is gene regulation, of course. That’s what establishes the difference between them. But this doesn’t get at that question.”
Britten writes that once a deletion occurs, it would be very unlikely that the missing sequence region would be reconstructed again through evolution. Therefore, the position and content of the inserted or deleted genetic information could be indispensable to mapping the course of human evolution.
“Everybody’s known about deletions, but there have been no opportunities to check them,” he says, explaining that until recently, the genomes hadn’t been unraveled enough to test the significance of indels. Traditionally, indels have been added to the base substitution count, regardless of length.
Forty years ago, Vincent Sarich and Allan Wilson stirred up controversy when they used immunological techniques to argue that apes were closer relatives to humans than previously believed. Wilson extended his research with Mary-Claire King in the 1970s, demonstrating via proteins that chimpanzees share our genetic makeup within a 2 percent divergence, thereby setting the 98.5 percent standard.
“The [traditional] 98 to 99 percent number refers to the [nonrepetitive] genomic regions that have a lot of active genes and a relatively smaller proportion of ‘junk DNA,’” explains Ajit Varki, professor of medicine and director of the Glycobiology Research and Training Center at the University of California at San Diego. “Dr. Britten is comparing large stretches of DNA that include both categories. So it is perhaps not surprising that the percent difference he finds is greater than the often-quoted 1 to 2 percent.”
Britten says he expects to see an increase in the inclusion of indels in other genome comparisons because it increases comparison-test sensitivity for closely related species by generating a more inclusive picture of the genomes in question.
Britten may take some flak from the evolutionary biology community for shaking up the family tree with the inclusion of indels. “Anytime you do anything with human evolution, you get into trouble,” he says.
Britten, R.J. Divergence between samples of chimpanzee and human DNA sequences is 5%, counting indels. Proceedings of the National Academy of Sciences 99 (21), 13633-13635: Oct. 15, 2002.