Emile Zuckerkandl
Encyclopedia
Emile Zuckerkandl is an Austrian-American biologist considered one of the founders of the field of molecular evolution
. He is best known for introducing, with Linus Pauling
, the concept of the molecular clock
, which set the stage for the neutral theory of molecular evolution
.
, Austria
in a household of intellectuals but his family moved in 1938 to Paris followed by Algiers to escape the Nazi persecution
of Jews
. At the end of World War II
, he spent one year at the Sorbonne
, then came to the United States
to study physiology—earning a master's degree in 1947 from the University of Illinois
, under C. Ladd Prosser—then returned to the Sorbonne to complete a Ph.D. in biology. Zuckerkandl developed a strong interest in molecular problems; his early research at a marine biology lab in Roscoff
focused on the roles copper oxidases and hemocyanin
in the molting cycles of crabs. In 1957, Zuckerkandl met renowned chemist Linus Pauling
, whose research interests were turning toward molecular diseases and molecular evolution as an outgrowth of his activism on nuclear issues. They arranged a post-doctoral fellowship, and Zuckerkandl (now with his wife Jane) returned to the United States to work with Pauling at Caltech
beginning in 1959.
and electrophoresis
that produced a two-dimensional pattern—to hemoglobin
. The peptide fragments of hemoglobin samples from different species, partially broken down by digestive enzyme
s, would produce unique patterns that could be used to estimate differences in protein structure. Zuckerkandl, Jones and Pauling published a comparison of several species' hemoglobin fingerprints in 1960, observing that the level of dissimilarity of protein fingerprints corresponded roughly to the phylogenetic distance between source species. However, the method was not conducive to quantitative comparisons, so Zuckerkandl began working on the determination of the actual peptide sequence
of the α and β chains of human
and gorilla
hemoglobin.
In 1962, Pauling and Zuckerkandl published their first paper using the molecular clock
concept (though not yet by that name). Like a number subsequent collaborative papers, it was not peer-reviewed—it was an invited paper in honor of Albert Szent-Györgyi
—and they intentionally took the opportunity to "say something outrageous". The paper used the number of differences in the α and β chains of hemoglobin to infer the time since the last common ancestor for a number of species, calibrated based on paleontological evidence for humans and horses. Though the paper did not provide any explanation for why amino acid differences in a protein should accumulate at a uniform rate (the essential assumption of the molecular clock), it did show that the results were fairly consistent with those of paleontologists.
In the following years, Zuckerkandl worked to refine the molecular clock. In 1963, he and Pauling coined the term "semantides" for biological sequences—DNA, RNA, and polypeptides—that hold evolutionary information and argued that such sequences could be the basis for constructing molecular phylogenies, suggesting that the molecular clock approach might be useful for other semantides besides proteins. Emanuel Margoliash
's first publication of sequence data for cytochrome c
allowed comparison of the rates of molecular evolution for different proteins (cytochrome c seemed to evolve faster than hemoglobin), which Zuckerkandl discussed at a 1964 conference in Bruges
. Zuckerkandl also adjusted the mathematics of the clock to account for the observation that some positions in an amino acid sequence were more stable than others, and the likelihood of multiple substitutions at the same position. In September 1964, he attended the landmark Evolving Genes and Proteins symposium, where he and Pauling presented their most influential paper ("Evolutionary Divergence and Convergence in Proteins", published in the conference proceedings the following year). The paper, primarily Zuckerkandl's work, named the evolutionary clock and presented a derivation of its basic mathematical form. Though Zuckerkandl and Pauling saw the clock as compatible with natural selection
, it would later become the foundation of the neutral theory of molecular evolution
, in which genetic drift
rather than selection is the driving force of evolution at the molecular level.
, and in the late 1970s became President of the Linus Pauling Institute
(then in 1992 of its successor, the Institute of Molecular Medical Sciences). His recent work includes criticism of social constructionism
and intelligent design
.
Molecular evolution
Molecular evolution is in part a process of evolution at the scale of DNA, RNA, and proteins. Molecular evolution emerged as a scientific field in the 1960s as researchers from molecular biology, evolutionary biology and population genetics sought to understand recent discoveries on the structure...
. He is best known for introducing, with Linus Pauling
Linus Pauling
Linus Carl Pauling was an American chemist, biochemist, peace activist, author, and educator. He was one of the most influential chemists in history and ranks among the most important scientists of the 20th century...
, the concept of the molecular clock
Molecular clock
The molecular clock is a technique in molecular evolution that uses fossil constraints and rates of molecular change to deduce the time in geologic history when two species or other taxa diverged. It is used to estimate the time of occurrence of events called speciation or radiation...
, which set the stage for the neutral theory of molecular evolution
Neutral theory of molecular evolution
The neutral theory of molecular evolution states that the vast majority of evolutionary changes at the molecular level are caused by random drift of selectively neutral mutants . The theory was introduced by Motoo Kimura in the late 1960s and early 1970s...
.
Life and work
Zuckerkandl was raised in ViennaVienna
Vienna is the capital and largest city of the Republic of Austria and one of the nine states of Austria. Vienna is Austria's primary city, with a population of about 1.723 million , and is by far the largest city in Austria, as well as its cultural, economic, and political centre...
, Austria
Austria
Austria , officially the Republic of Austria , is a landlocked country of roughly 8.4 million people in Central Europe. It is bordered by the Czech Republic and Germany to the north, Slovakia and Hungary to the east, Slovenia and Italy to the south, and Switzerland and Liechtenstein to the...
in a household of intellectuals but his family moved in 1938 to Paris followed by Algiers to escape the Nazi persecution
Racial policy of Nazi Germany
The racial policy of Nazi Germany was a set of policies and laws implemented by Nazi Germany, asserting the superiority of the "Aryan race", and based on a specific racist doctrine which claimed scientific legitimacy...
of Jews
Jews
The Jews , also known as the Jewish people, are a nation and ethnoreligious group originating in the Israelites or Hebrews of the Ancient Near East. The Jewish ethnicity, nationality, and religion are strongly interrelated, as Judaism is the traditional faith of the Jewish nation...
. At the end of World War II
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...
, he spent one year at the Sorbonne
Sorbonne
The Sorbonne is an edifice of the Latin Quarter, in Paris, France, which has been the historical house of the former University of Paris...
, then came to the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
to study physiology—earning a master's degree in 1947 from the University of Illinois
University of Illinois at Urbana-Champaign
The University of Illinois at Urbana–Champaign is a large public research-intensive university in the state of Illinois, United States. It is the flagship campus of the University of Illinois system...
, under C. Ladd Prosser—then returned to the Sorbonne to complete a Ph.D. in biology. Zuckerkandl developed a strong interest in molecular problems; his early research at a marine biology lab in Roscoff
Roscoff
Roscoff is a commune in the Finistère department of Brittany in northwestern France.The nearby Île de Batz, called Enez Vaz in Breton, is a small island that can be reached by launch from the harbour....
focused on the roles copper oxidases and hemocyanin
Hemocyanin
Hemocyanins are respiratory proteins in the form of metalloproteins containing two copper atoms that reversibly bind a single oxygen molecule . Oxygenation causes a color change between the colorless Cu deoxygenated form and the blue Cu oxygenated form...
in the molting cycles of crabs. In 1957, Zuckerkandl met renowned chemist Linus Pauling
Linus Pauling
Linus Carl Pauling was an American chemist, biochemist, peace activist, author, and educator. He was one of the most influential chemists in history and ranks among the most important scientists of the 20th century...
, whose research interests were turning toward molecular diseases and molecular evolution as an outgrowth of his activism on nuclear issues. They arranged a post-doctoral fellowship, and Zuckerkandl (now with his wife Jane) returned to the United States to work with Pauling at Caltech
California Institute of Technology
The California Institute of Technology is a private research university located in Pasadena, California, United States. Caltech has six academic divisions with strong emphases on science and engineering...
beginning in 1959.
Linus Pauling and the molecular clock hypothesis
Zuckerkandl's first project under Pauling (working with graduate student Richard T. Jones) was the application of new protein fingerprinting techniques—a combination of paper chromatographyPaper chromatography
Paper chromatography is an analytical chemistry technique for separating and identifying mixtures that are or can be colored, especially pigments. This can also be used in secondary or primary colors in ink experiments. This method has been largely replaced by thin layer chromatography, however it...
and electrophoresis
Electrophoresis
Electrophoresis, also called cataphoresis, is the motion of dispersed particles relative to a fluid under the influence of a spatially uniform electric field. This electrokinetic phenomenon was observed for the first time in 1807 by Reuss , who noticed that the application of a constant electric...
that produced a two-dimensional pattern—to hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
. The peptide fragments of hemoglobin samples from different species, partially broken down by digestive enzyme
Digestive enzyme
'Digestive enzymes' are enzymes that break down polymeric macromolecules into their smaller building blocks, in order to facilitate their absorption by the body. Digestive enzymes are found in the digestive tract of animals where they aid in the digestion of food as well as inside the cells,...
s, would produce unique patterns that could be used to estimate differences in protein structure. Zuckerkandl, Jones and Pauling published a comparison of several species' hemoglobin fingerprints in 1960, observing that the level of dissimilarity of protein fingerprints corresponded roughly to the phylogenetic distance between source species. However, the method was not conducive to quantitative comparisons, so Zuckerkandl began working on the determination of the actual peptide sequence
Peptide sequence
Peptide sequence or amino acid sequence is the order in which amino acid residues, connected by peptide bonds, lie in the chain in peptides and proteins. The sequence is generally reported from the N-terminal end containing free amino group to the C-terminal end containing free carboxyl group...
of the α and β chains of human
Human
Humans are the only living species in the Homo genus...
and gorilla
Gorilla
Gorillas are the largest extant species of primates. They are ground-dwelling, predominantly herbivorous apes that inhabit the forests of central Africa. Gorillas are divided into two species and either four or five subspecies...
hemoglobin.
In 1962, Pauling and Zuckerkandl published their first paper using the molecular clock
Molecular clock
The molecular clock is a technique in molecular evolution that uses fossil constraints and rates of molecular change to deduce the time in geologic history when two species or other taxa diverged. It is used to estimate the time of occurrence of events called speciation or radiation...
concept (though not yet by that name). Like a number subsequent collaborative papers, it was not peer-reviewed—it was an invited paper in honor of Albert Szent-Györgyi
Albert Szent-Györgyi
Albert Szent-Györgyi de Nagyrápolt was a Hungarian physiologist who won the Nobel Prize in Physiology or Medicine in 1937. He is credited with discovering vitamin C and the components and reactions of the citric acid cycle...
—and they intentionally took the opportunity to "say something outrageous". The paper used the number of differences in the α and β chains of hemoglobin to infer the time since the last common ancestor for a number of species, calibrated based on paleontological evidence for humans and horses. Though the paper did not provide any explanation for why amino acid differences in a protein should accumulate at a uniform rate (the essential assumption of the molecular clock), it did show that the results were fairly consistent with those of paleontologists.
In the following years, Zuckerkandl worked to refine the molecular clock. In 1963, he and Pauling coined the term "semantides" for biological sequences—DNA, RNA, and polypeptides—that hold evolutionary information and argued that such sequences could be the basis for constructing molecular phylogenies, suggesting that the molecular clock approach might be useful for other semantides besides proteins. Emanuel Margoliash
Emanuel Margoliash
Emanuel Margoliash was a biochemist who spent much of his career studying the protein cytochrome c. He is best known for his work on molecular evolution; with Walter Fitch, he devised Fitch-Margoliash method for constructing evolutionary trees based on protein sequences.He was a member of the...
's first publication of sequence data for cytochrome c
Cytochrome c
The Cytochrome complex, or cyt c is a small heme protein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins. Cytochrome c is a highly soluble protein, unlike other cytochromes, with a solubility of about 100 g/L and is an...
allowed comparison of the rates of molecular evolution for different proteins (cytochrome c seemed to evolve faster than hemoglobin), which Zuckerkandl discussed at a 1964 conference in Bruges
Bruges
Bruges is the capital and largest city of the province of West Flanders in the Flemish Region of Belgium. It is located in the northwest of the country....
. Zuckerkandl also adjusted the mathematics of the clock to account for the observation that some positions in an amino acid sequence were more stable than others, and the likelihood of multiple substitutions at the same position. In September 1964, he attended the landmark Evolving Genes and Proteins symposium, where he and Pauling presented their most influential paper ("Evolutionary Divergence and Convergence in Proteins", published in the conference proceedings the following year). The paper, primarily Zuckerkandl's work, named the evolutionary clock and presented a derivation of its basic mathematical form. Though Zuckerkandl and Pauling saw the clock as compatible with natural selection
Natural selection
Natural selection is the nonrandom process by which biologic traits become either more or less common in a population as a function of differential reproduction of their bearers. It is a key mechanism of evolution....
, it would later become the foundation of the neutral theory of molecular evolution
Neutral theory of molecular evolution
The neutral theory of molecular evolution states that the vast majority of evolutionary changes at the molecular level are caused by random drift of selectively neutral mutants . The theory was introduced by Motoo Kimura in the late 1960s and early 1970s...
, in which genetic drift
Genetic drift
Genetic drift or allelic drift is the change in the frequency of a gene variant in a population due to random sampling.The alleles in the offspring are a sample of those in the parents, and chance has a role in determining whether a given individual survives and reproduces...
rather than selection is the driving force of evolution at the molecular level.
Later work
In 1965, Zuckerkandl moved back to France to direct the "Centre de recherches de biochimie macromoléculaire" of the Centre National de Recherche Scientifique. In 1971, he became the founding editor of the Journal of Molecular EvolutionJournal of Molecular Evolution
The Journal of Molecular Evolution is a peer-reviewed scientific journal that covers molecular evolution. The journal is published by Springer and was established in 1971. The founding editor is Emile Zuckerkandl, who remained editor in chief until the late 1990s...
, and in the late 1970s became President of the Linus Pauling Institute
Linus Pauling Institute
The Linus Pauling Institute is a research institute located at Oregon State University with a focus on health maintenance. The mission statement of the institute is three-fold. First, to determine the functional roles of micronutrients and phytochemicals in promoting optimal health and to treat or...
(then in 1992 of its successor, the Institute of Molecular Medical Sciences). His recent work includes criticism of social constructionism
Social constructionism
Social constructionism and social constructivism are sociological theories of knowledge that consider how social phenomena or objects of consciousness develop in social contexts. A social construction is a concept or practice that is the construct of a particular group...
and intelligent design
Intelligent design
Intelligent design is the proposition that "certain features of the universe and of living things are best explained by an intelligent cause, not an undirected process such as natural selection." It is a form of creationism and a contemporary adaptation of the traditional teleological argument for...
.