The Molecular Clock Problem

It is often convenient for evolutionary biologists to assume that certain proteins evolve at a fixed rate. Such proteins can be used as ``molecular clocks,'' since one can use them to estimate when species diverged. However, these clocks sometimes behave in an erratic manner which calls into question their use and even the entire theory of evolution. The paper, Vagaries of the molecular clock, by Francisco J. Ayala, from Proc. Natl. Acad. Sci. USA Vol. 94, pp. 7776-7783, July 1997, illustrates some of the problems with the so-called molecular clocks. The abstract follows:

The hypothesis of the molecular evolutionary clock asserts that informational macromolecules (i.e., proteins and nucleic acids) evolve at rates that are constant through time and for different lineages. The clock hypothesis has been extremely powerful for determining evolutionary events of the remote past for which the fossil and other evidence is lacking or insufficient. I review the evolution of two genes, Gpdh and Sod. In fruit flies, the encoded glycerol-3-phosphate dehydrogenase (GPDH) protein evolves at a rate of 1.1 x 10¹⁰ amino acid replacements per site per year when Drosophila species are compared that diverged within the last 55 million years (My), but a much faster rate of 4.5 x 10¹⁰ replacements per site per year when comparisons are made between mammals (70 My) or Dipteran families (100 My), animal phyla (650 My), or multicellular kingdoms (1100 My). The rate of superoxide dismutase (SOD) evolution is very fast between Drosophila species (16.2 x 10¹⁰ replacements per site per year) and remains the same between mammals (17.2) or Dipteran families (15.9), but it becomes much slower between animal phyla (5.3) and still slower between the three kingdoms (3.3). If we assume a molecular clock and use the Drosophila rate for estimating the divergence of remote organisms, GPDH yields estimates of 2,500 My for the divergence between the animal phyla (occurred 650 My) and 3,990 My for the divergence of the kingdoms (occurred 1,100 My). At the other extreme, SOD yields divergence times of 211 My and 224 My for the animal phyla and the kingdoms, respectively. It remains unsettled how often proteins evolve in such erratic fashion as GPDH and SOD.

The text of the paper reveals the puzzlement of the authors as to how this could occur.

Another possible instance of this is the paper ``Recent African origin of modern humans revealed by complete sequences of hominoid mitochondrial DNAs'' by S. Horai, K. Hayasaka, R. Kondo, K. Tsugane, and N. Takahata (Proc. Natl. Acad. Sci. USA 1995 Jan 17;92(2):532-536). They compared 3754 third codon positions in the mitochondrial DNA and found a .381 (about 38 percent) difference between humans and chimpanzees. Incidentally, this seems to be a rather large difference! In humans, they found that the D-loop region of mitochondrial DNA evolves about 1.8 times faster than the synonomous sites. This would seem to imply that humans and chimpanzees should differ by about 1.8 times .381 or about .684 (over 68 percent) in the D-loop region. But in fact in this region, which has 1105 base pairs, there are about 146 differences between humans and chimpanzees, which is thus about a 13.2 percent difference. Even if all of these differences are in the hyper-variable segments I and II having 758 base pairs, the percentage there is only about 19.3 percent. So why should the D-loop region evolve much faster than synonomous sites in humans but much slower when comparing humans and chimpanzees? Unless I am somehow misunderstanding the article, this is another evolutionary puzzle.

One resolution of the difficulty is to assume that apes and humans have always been different, and that the third codon positions were very different at the start.

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