2007/05/01 by Naoyuki Takahata · 1 citation
Biochemistry, Genetics and Molecular Biology · #Bioinformatics and Genomic Networks #Biology #Darwinism #Divergence (linguistics) #Evolution and Genetic Dynamics #Evolutionary biology #Gene #Genetics #Molecular clock #Philosophy #Phylogenetics #RNA and protein synthesis mechanisms
paper · doi:10.1534/genetics.104.75135
openalex publication_date 2007/05/01 · openalex created_date 2016/06/24 · openalex updated_date 2026/03/20
S early as the time of the rediscovery of Mendel’slaws, George H. F. Nuttal measured the amount ofprecipitateofnormalserafromgreatapes,monkeys,andsome other mammals. His crude method, using rabbitantiserum directed against whole human serum, in-dicated that except for flying lemurs, the amount ofprecipitatedeclinedwiththeevolutionarydistancefromhumans (Nuttal 1904; Klein 1995). The immunolog-ical method was later refined and played an importantrole in reconstructing primate phylogenies (Goodman1962). In 1962, almost in parallel, Emile Zuckerkandlcollaborated with Linus Pauling at Caltech on hemoglo-bin evolution and expressed the idea of ‘‘molecular an-thropology’’asanewdiscipline(Z uckerkandl1963).Theidea was optimistic and ahead of the times, but MorrisGoodman shared it. In the same year, Zuckerkandland Pauling (1962) calibrated the amino acid substi-tution rate in mammalian hemoglobins and estimatedthe divergence times of orthologous and paralogoushemoglobins. Clearly, the immunological and proteinsequence data had already provided the germ for im-munological and protein clocks (see also Margoliash1963 for cytochrome c; Doolittle and Blomba¨ck1964for fibrinopeptides).The time was ripe for Zuckerkandl and Pauling(1965, p. 138) to advocate the concept of a molecularevolutionary clock: ‘‘Anyone who recognizes the valueof the immunological approach for estimating phyleticdistance with certain limits should find it impossible todeny that the comparison of amino acid sequences ispotentially an even better tool. It is only potentially lessequivocal, more accurate, suited for absolute instead ofonly relative evaluations, and able to extrapolate fromthe present to the past.’’ The stochastic nature of themolecular clock was well recognized and described by aPoisson process for the first time. It was also pointed outthat, for a molecular clock to exist, amino acid changesmust be limited almost exclusively to functionally nearlyneutral changes, although not only random genetic driftbut also Darwinian selection was invoked for fixation ofsuch changes. Thus, the discovery of a molecular clocksupportedtheconceptofnearneutrality at the molecularlevel. From a historical point of view, it is of interest to askwho was responsible for the monumental proposition of amolecular clock, Zuckerkandl or Pauling. Thirty yearslater, Pauling recalled, ‘‘I think it was my idea, but I amnot sure. We were just collaborating on these studies.Perhaps it was Emile’s idea’’ (M organ 1998, p. 166).This recollection might be a Freudian memory lapse (E.Zuckerkandl, personal communication). The idea mustbe Emile Zuckerkandl’s, since it is clear in Z uckerkandland Pauling (1962), an article almost entirely writtenby Zuckerkandl (see also Zuckerkandl 1987).The high evolutionary rate estimated from hemoglo-bin and other proteins was a key to development of theneutral theory by Motoo Kimura, rather than, as some-times asserted, the large extent of electrophoreticallyobserved polymorphism (Dietrich 1994; Sua´rez andBarahona 1996). Indeed, Kimura’s 1968 article beginswith a discussion of the amino acid substitution rate ob-tained from Zuckerkandl and Pauling (1965). Fromthis, Kimura estimated the nucleotide substitution rateon the basis of codon degeneracy and extrapolated thisratetotheentiregenomeonthebasisofthetotalnumberof base pairs estimated by Muller (1958). This rate wastoo high to be accounted for by natural selection, ac-cording to Haldane’s (1957) cost of natural selection.Kimura often said that Muller’s estimate (4 3 10