Differences With the Relatives

By lining up chimp chromosome 22 and human chromosome 21 and comparing them nucleotide by nucleotide, the consortium found instances in which one nucleotide was substituted for another in only about 1.44% of the sequence. The chimpanzee chromosome has been sequenced to an accuracy of less than one error in 104 bases, so sequencing mistakes account for less than 1% of the observed single-nucleotide mismatches. There is also an impressive number (68,000) of small to large stretches of DNA that have been either gained or lost (these are celled ‘insertions or deletions’, ‘indels’ for short) in one species or the other.

The number of single-nucleotide substitutions is in the range found in earlier studies, but the frequency and size of the indels are more of a surprise. Although most of the indels are less than 30 nucleotides long, some attain sizes of up to 54,000 nucleotides. Those of about 300 nucleotides or more frequently involve transposable elements – DNA sequences that multiply and insert new copies of themselves throughout a genome. For a subset of these 300-nucelotide-plus indels, the authors were able to extend the comparison to other great apes: gorillas and orang-utans. They could thereby infer the lineage (chimp or human) in which the alterations occurred, and could distinguish between insertions and deletions – that is, whether a given sequence was added in one lineage or deleted in the other. These comparisons show that insertions of about 300 nucleotides, mainly of the type of transposable element known as an Alu repeat, have occurred preferentially in the human lineage. Deletions and other insertions seem to have occurred at similar frequencies in both lineages.

Even if the major physical, physiological and behavioural differences between the two species do not result simply from an accumulation of many small alterations, the challenge to find the most crucial changes is still ahead. For example, the FOXP2 gene product, which is important for language development, differs by two amino acids in humans and chimps, suggesting that the gene has been a target of selection in the human lineage. Yet the role of this gene in language was suggested not by human-chimp comparisons but by mutation studies in humans.

Identifying sequence changes in the chimpanzee lineage that are likely to have been irrelevant to the acquisition of human-specific traits will depend on sequence comparisons with other great apes. Do we now need the gorilla genome sequence to shed more light on the questions raised by comparing human and chimp DNA?