Editing Molecular clock (section)

==Early discovery and genetic equidistance==
The notion of the existence of a so-called "molecular clock" was first attributed to [[Emile Zuckerkandl|Émile Zuckerkandl]] and [[Linus Pauling]] who, in 1962, noticed that the number of [[amino acid]] differences in [[hemoglobin]] between different lineages changes roughly [[Linear function|linearly]] with time, as estimated from fossil evidence.<ref name=Zuckerkand62>{{cite book | vauthors = Zuckerkandl E, Pauling | author-link1 = Emile Zuckerkandl | author-link2 = Linus Pauling | year = 1962 | title = Horizons in Biochemistry | chapter-url = https://archive.org/details/horizonsinbioche0000kash| chapter-url-access = registration| chapter = Molecular disease, evolution, and genic heterogeneity |editor=Kasha, M. |editor2=Pullman, B| pages = [https://archive.org/details/horizonsinbioche0000kash/page/189 189–225] | publisher = Academic Press, New York}}</ref> They generalized this observation to assert that the rate of [[evolution]]ary change of any specified [[protein]] was approximately constant over time and over different lineages (known as the '''molecular clock hypothesis''').

The '''genetic equidistance''' phenomenon was first noted in 1963 by [[Emanuel Margoliash]], who wrote: "It appears that the number of residue differences between [[cytochrome c]] of any two species is mostly conditioned by the time elapsed since the lines of evolution leading to these two species originally diverged. If this is correct, the cytochrome c of all mammals should be equally different from the cytochrome c of all birds. Since fish diverges from the main stem of vertebrate evolution earlier than either birds or mammals, the cytochrome c of both mammals and birds should be equally different from the cytochrome c of fish. Similarly, all vertebrate cytochrome c should be equally different from the yeast protein."<ref>{{cite journal | vauthors = Margoliash E | title = Primary Structure and Evolution of Cytochrome C | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 50 | issue = 4 | pages = 672–679 | date = October 1963 | pmid = 14077496 | pmc = 221244 | doi = 10.1073/pnas.50.4.672 | doi-access = free | bibcode = 1963PNAS...50..672M }}</ref> For example, the difference between the cytochrome c of a carp and a frog, turtle, chicken, rabbit, and horse is a very constant 13% to 14%. Similarly, the difference between the cytochrome c of a bacterium and yeast, wheat, moth, tuna, pigeon, and horse ranges from 64% to 69%. Together with the work of Emile Zuckerkandl and Linus Pauling, the genetic equidistance result led directly to the formal postulation of the molecular clock hypothesis in the early 1960s.<ref>{{cite journal | vauthors = Kumar S | title = Molecular clocks: four decades of evolution | journal = Nature Reviews. Genetics | volume = 6 | issue = 8 | pages = 654–662 | date = August 2005 | pmid = 16136655 | doi = 10.1038/nrg1659 | s2cid = 14261833 }}</ref>

Similarly, [[Vincent Sarich]] and [[Allan Wilson (biologist)|Allan Wilson]] in 1967 demonstrated that molecular differences among modern [[primate]]s in [[albumin]] proteins showed that approximately constant rates of change had occurred in all the lineages they assessed.<ref>{{cite journal | vauthors = Sarich VM, Wilson AC | title = Rates of albumin evolution in primates | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 58 | issue = 1 | pages = 142–148 | date = July 1967 | pmid = 4962458 | pmc = 335609 | doi = 10.1073/pnas.58.1.142 | doi-access = free | bibcode = 1967PNAS...58..142S }}</ref> The basic logic of their analysis involved recognizing that if one species lineage had evolved more quickly than a sister species lineage since their common ancestor, then the molecular differences between an outgroup (more distantly related) species and the faster-evolving species should be larger (since more molecular changes would have accumulated on that lineage) than the molecular differences between the outgroup species and the slower-evolving species. This method is known as the [[relative rate test]]. Sarich and Wilson's paper reported, for example, that human (''[[Homo sapiens]]'') and chimpanzee (''[[Common chimpanzee|Pan troglodytes]]'') albumin immunological cross-reactions suggested they were about equally different from [[New World monkey|Ceboidea]] (New World Monkey) species (within experimental error). This meant that they had both accumulated approximately equal changes in albumin since their shared common ancestor. This pattern was also found for all the primate comparisons they tested. When calibrated with the few well-documented fossil branch points (such as no Primate fossils of modern aspect found before the [[Cretaceous–Paleogene boundary|K-T boundary]]), this led Sarich and Wilson to argue that the human-chimp divergence probably occurred only ~4–6 million years ago.<ref>{{cite journal | vauthors = Sarich VM, Wilson AC | title = Immunological time scale for hominid evolution | journal = Science | volume = 158 | issue = 3805 | pages = 1200–1203 | date = December 1967 | pmid = 4964406 | doi = 10.1126/science.158.3805.1200 | s2cid = 7349579 | bibcode = 1967Sci...158.1200S | jstor = 1722843 }}</ref>