Manipulating Underdetermination in Scientific Controversy: the Case of the Molecular Clock
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THE AVERAGE NUMBER OF GENERATIONS UNTIL EXTINCTION OF AN INDIVIDUAL MUTANT GENE IN A FINITE POPULATION MOT00 KIMURA' AND TOMOKO OHTA Department of Biology, Princeton University and National Institute of Genetics, Mishima, Japan Received June 13, 1969 AS pointed out by FISHER(1930), a majority of mutant genes which appear in natural populations are lost by chance within a small number of genera- tions. For example, if the mutant gene is selectively neutral, the probability is about 0.79 that it is lost from the population during the first 7 generations. With one percent selective advantage, this probability becomes about 0.78, namely, it changes very little. In general, the probability of loss in early generations due to random sampling of gametes is very high. The question which naturally follows is how long does it take, on the average, for a single mutant gene to become lost from the population, if we exclude the cases in which it is eventually fixed (established) in the population. In the present paper, we will derive some approximation formulas which are useful to answer this question, based on the theory of KIMURAand OHTA(1969). Also, we will report the results of Monte Carlo experiments performed to check the validity of the approximation formulas. APPROXIMATION FORMULAS BASED ON DIFFUSION MODELS Let us consider a diploid population, and denote by N and Ne, respectively, its actual and effective sizes. The following treatment is based on the diffusion models of population genetics (cf. KIMURA1964). As shown by KIMURAand OHTA (1969), if p is the initial frequency of the mutant gene, the average number of generations until loss of the mutant gene (excluding the cases of its eventual fixation) is - In this formula, 1 On leave from the National Institute of Genetics, Mishima, Japan. -
Molecular Evolution
An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Molecular Evolution An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Outline • Evolutionary Tree Reconstruction • “Out of Africa” hypothesis • Did we evolve from Neanderthals? • Distance Based Phylogeny • Neighbor Joining Algorithm • Additive Phylogeny • Least Squares Distance Phylogeny • UPGMA • Character Based Phylogeny • Small Parsimony Problem • Fitch and Sankoff Algorithms • Large Parsimony Problem • Evolution of Wings • HIV Evolution • Evolution of Human Repeats An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Early Evolutionary Studies • Anatomical features were the dominant criteria used to derive evolutionary relationships between species since Darwin till early 1960s • The evolutionary relationships derived from these relatively subjective observations were often inconclusive. Some of them were later proved incorrect An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Evolution and DNA Analysis: the Giant Panda Riddle • For roughly 100 years scientists were unable to figure out which family the giant panda belongs to • Giant pandas look like bears but have features that are unusual for bears and typical for raccoons, e.g., they do not hibernate • In 1985, Steven O’Brien and colleagues solved the giant panda classification problem using DNA sequences and algorithms An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Evolutionary Tree of Bears and Raccoons An Introduction to Bioinformatics Algorithms www.bioalgorithms.info Evolutionary Trees: DNA-based Approach • 40 years ago: Emile Zuckerkandl and Linus Pauling brought reconstructing evolutionary relationships with DNA into the spotlight • In the first few years after Zuckerkandl and Pauling proposed using DNA for evolutionary studies, the possibility of reconstructing evolutionary trees by DNA analysis was hotly debated • Now it is a dominant approach to study evolution. -
Concentration-Affinity Equivalence in Gene Regulation: Convergence Of
Proc. Nad. Acad. Sci. USA Vol. 85, pp. 4784-4788, July 1988 Evolution Concentration-affinity equivalence in gene regulation: Convergence of genetic and environmental effects (phenocopies/parallel evolution/genetic assimilation/expressivity/penetrance) EMILE ZUCKERKANDL* AND RUXTON VILLETt *Linus Pauling Institute of Science and Medicine, 440 Page Mill Road, Palo Alto, CA 94306; and tU.S. Department of Agriculture, Agricultural Research Services, National Program Staff, Building 05S, BARC-West, Beltsville, MD 20705 Communicated by Francisco J. Ayala, March 21, 1988 ABSTRACT It is proposed that equivalent phenotypic affinity can also be altered by a reversible structural change effects can be obtained by either structural changes in macro- in the protein, resulting in a modification of specific fit molecules involved in gene regulation or changes in activity of between macromolecules and brought about by a combina- the structurally unaltered macromolecules. This equivalence tion with, or by the release of, an effector. An important between changes in activity (concentration) and changes in variant of the latter process is a reversible formation of a structure can come into play within physiologically plausible covalent compound between a polynucleotide-binding pro- limits and seems to represent an important interface between tein and some other organic moiety (e.g., acetylation, ADP- environment and genome-namely, between environmentally ribosylation; see ref. 6). The potential equivalence is between determined and genetically determined gene expression. The the effect of a change in component concentration (activity) equivalence principle helps explain the appearance of pheno- under a constant structural state and the effect ofa structural copies. It also points to a general pathway favorable to the modification under constant component concentration (ac- occurrence, during evolution, offrequent episodes correspond- tivity). -
National Institute of Genetics Japan
NATIONAL INSTITUTE OF GENETICS JAPAN ANNUAL REPORT No. 20 1969 Publi8l&ed bll THE NATIONAL INS'ITI'UTE OF GENETICS Mitlima. Simoka-ken. Japtm 1970 Annual Report of the National Institute of Genetics No. 20, 1969 Published by The National Institute of Genetics, Japan 1970 CONTENTS General statement 1 Staff..................................... .. 2 Council............................................................ 5 Association for propagation of the knowledge of genetics... 5 Projects of research for 1969 ................ 6 Researches carried out in 1969 .......................... 9 1. Cytogenetics Segregation of three types of the largest No.1 (A-I) chromosome in Rattus rattus bred in a population room. YOSIDA, T. H. and TSUCHIYA, K. 9 Polymorphism of No.9 (A-9) and No. 13 (A-13) autosomes in Rattus rattus collected in Japan. YOSIDA, T. H. and TSUCHIYA, K. and MASUJI, H.......................................... 10 Frequency of chromosome polymorphism in Rattus rattus col- lected in East and Southeast Asia. YOSIDA, T. H. and TSUCHIYA, K. 11 Fl and F2 hybrids between Asian and Oceanian black rats with different karyotypes. YOSIDA, T. H., KATO, H. and SAKAKI- BARA, K.................................................... 13 Karyotypes of black rats, Rattus rattus, obtained from Honolulu, Hawaii. YOSIDA, T. H. and TSUCHIYA, K. 14 Local differences in the frequencies of chromosome polymorphism in the house rat, Rattus rattus, in Japan. YOSIDA, T. H., TSUCHIYA, K. and SONODA, J. 15 Karyotypes of Rattus bowersii collected in Malaysia. YOSIDA, T. H. and TSUCHIYA, K. 16 Protective effects of protamine sulfate on disintegration of isolated metaphase chromosomes. KATO, H., SEKIYA, K. and YOSIDA, T. H. 17 A preliminary study on the uptake of isolated nuclei by mam malian cells in vitro. -
MOLECULAR CLOCKS Definition Introduction
MOLECULAR CLOCKS 583 Kishino, H., Thorne, J. L., and Bruno, W. J., 2001. Performance of Thorne, J. L., Kishino, H., and Painter, I. S., 1998. Estimating the a divergence time estimation method under a probabilistic model rate of evolution of the rate of molecular evolution. Molecular of rate evolution. Molecular Biology and Evolution, 18,352–361. Biology and Evolution, 15, 1647–1657. Kodandaramaiah, U., 2011. Tectonic calibrations in molecular dat- Warnock, R. C. M., Yang, Z., Donoghue, P. C. J., 2012. Exploring ing. Current Zoology, 57,116–124. uncertainty in the calibration of the molecular clock. Biology Marshall, C. R., 1997. Confidence intervals on stratigraphic ranges Letters, 8, 156–159. with nonrandom distributions of fossil horizons. Paleobiology, Wilkinson, R. D., Steiper, M. E., Soligo, C., Martin, R. D., Yang, Z., 23, 165–173. and Tavaré, S., 2011. Dating primate divergences through an Müller, J., and Reisz, R. R., 2005. Four well-constrained calibration integrated analysis of palaeontological and molecular data. Sys- points from the vertebrate fossil record for molecular clock esti- tematic Biology, 60,16–31. mates. Bioessays, 27, 1069–1075. Yang, Z., and Rannala, B., 2006. Bayesian estimation of species Parham, J. F., Donoghue, P. C. J., Bell, C. J., et al., 2012. Best practices divergence times under a molecular clock using multiple fossil for justifying fossil calibrations. Systematic Biology, 61,346–359. calibrations with soft bounds. Molecular Biology and Evolution, Peters, S. E., 2005. Geologic constraints on the macroevolutionary 23, 212–226. history of marine animals. Proceedings of the National Academy Zuckerkandl, E., and Pauling, L., 1962. Molecular disease, evolution of Sciences, 102, 12326–12331. -
What Is the Viewpoint of Hemoglobin, and Does It Matter?
Hist. Phil. Life Sci., 31 (2009), 241-262 What is the Viewpoint of Hemoglobin, and Does It Matter? Jonathan Marks University of North Carolina at Charlotte Department of Anthropology Charlotte, NC 28223, USA ABSTRACT - In this paper I discuss reductive trends in evolutionary anthropology. The first involved the reduction of human ancestry to genetic relationships (in the 1960s) and the second involved a parallel reduction of classification to phylogenetic retrieval (in the 1980s). Neither of these affords greater accuracy than their alternatives; that is to say, their novelty is epistemic, not empirical. As a result, there has been a revolution in classification in evolutionary anthropology, which arguably clouds the biological relationships of the relevant species, rather than clarifying them. Just below the species level, another taxonomic issue is raised by the reinscription of race as a natural category of the human species. This, too, is driven by the convergent interests of cultural forces including conservative political ideologies, the creation of pharmaceutical niche markets, free-market genomics, and old- fashioned scientific racism. KEYWORDS – Molecular anthropology, Systematics, Classification, Human evolution Introduction In this paper I explore the intersection of genetics, taxonomy, and evolutionary anthropology. All three fields are scientific areas saturated with cultural meanings and associations. First, genetics is the scientific study of heredity, but has historically capitalized on non-scientific prejudices about heredity to curry support: hence James Watson’s epigrammatic proclamation in support of the Human Genome Project, “We used to think our fate was in the stars. Now we know, in large measure, our fate is in our genes” (Jaroff 1989; Duster 1990; Nelkin and Lindee 1995). -
The Average Number of Generations Until Fixation of a Mutant Gene in a Finite Population'
THE AVERAGE NUMBER OF GENERATIONS UNTIL FIXATION OF A MUTANT GENE IN A FINITE POPULATION' MOT00 KIMURA AND TOMOKO OHTA, National Institute of Genetics, Mishima, Japan Received July 26, 1968 A mutant gene which appeared in a finite population will eventually either be lost from the population or fixed (established) in it. The mean time until either of these alternative events takes place was studied by WATTERSON(1962) and EWENS(1963). They made use of a method previously announced by DARL- ING and SIEGERT(1953), and, independently by FELLER(1954). Actually, DARL- ING and SIEGERTrefer to its application to genetics. From the standpoint of population genetics, however, it is much more desirable to determine separately the mean time until fixation and that until loss. Since the gene substitution in a population plays a key role in the evolution of the species, it may be of particular interest to know the mean time for a rare mutant gene to become fixed in a finite population, excluding the cases in which such a gene is lost from the population. In the present paper, a solution to this problem will be presented together with Monte Carlo experiments to test some of the theoretical results. Throughout this paper, the senior author (M. K.) is responsible for the mathematical treatments, while the junior author (T. 0.) is responsible for the numerical treatments based on computers. BASIC THEORY Let us consider a diploid population consisting of N individuals and having the variance effective number Ne, which may be different from the actual number (for the definition of Ne, see KIMURAand CROW1963). -
National Institute of Genetics Japan
NATIONAL INSTITUTE OF GENETICS JAPAN ANNUAL REPORT No. 19 1968 Published bll THE NATIONAL INSTITUTE OF GENETICS Misima. Sizuoka·ken, Japan 1969 Annual Report of the National Institute of Genetics No. 19, 1968 Published by The National Institute of Genetics, Japan 1969 CONTENTS General statement. ................................................. 1 Research member.................................................. 2 Council............................................................ 5 Projects of research for 1968....................................... 6 Researches carried out in 1968 ..................................... 9 I. Cytogenetics Scientific expedition for the study of rodents to South East Asia and Oceania. I. Members, aims and schedule of the scienti- fic expedition. YOSIDA, T. H. 9 Scientific expedition for the study of rodents to South East Asia and Oceania. II. Species and chromosome numbers of rodents collected from South East Asia and Oceania. YOSIDA, T. H., TSUCHlYA, K. and IMAI, H. T......................... 10 Scientific expedition for the study of rodents to South East Asia and Oceania. III. Chromosomal polymorphism and new karyotypes of black rat, Rattus rattus, collected in South East Asia and Oceania. YOSIDA, T. H. and TSUCHIYA, K......... 11 Scientific expedition for the study of rodents to South East Asia and Oceania. IV. Comparative idiogram analysis in several species belonging to genus Rattus collected from South East Asia and Oceania. YOSIDA, T. H. and TSUCHlYA, K......... 12 Scientific expedition for the study of rodents to South East Asia and Oceania. V. Breeding of wild rodents collected from South East Asia and Oceania. TSUCHIYA, K., YOSIDA, T. H... 13 Rat metaphase chromosomes incorporated into mouse metaphase cells. YOSIDA, T. H. and SEKIGUCHl, T...................... 15 Autoradiographic analysis of the rate of protein synthesis in diploid and tetraploid MSPC-l myeloma cells. -
The Neoselectionist Theory of Genome Evolution
The neoselectionist theory of genome evolution Giorgio Bernardi* Molecular Evolution Laboratory, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples, Italy Edited by Tomoko Ohta, National Institute of Genetics, Mishima, Japan, and approved April 4, 2007 (received for review February 22, 2007) The vertebrate genome is a mosaic of GC-poor and GC-rich isoch- of chance in evolution. A very significant modification of the ores, megabase-sized DNA regions of fairly homogeneous base neutral theory was the nearly neutral theory of Ohta (11, 12), composition that differ in relative amount, gene density, gene who proposed that a substantial fraction of changes are caused expression, replication timing, and recombination frequency. At by random fixation of nearly neutral changes, a class that the emergence of warm-blooded vertebrates, the gene-rich, mod- ‘‘includes intermediates between neutral and advantageous, as erately GC-rich isochores of the cold-blooded ancestors underwent well as between neutral and deleterious classes’’ (13). The first a GC increase. This increase was similar in mammals and birds and four schemes of Fig. 1 display a qualitative picture of the classical was maintained during the evolution of mammalian and avian theories just mentioned. orders. Neither the GC increase nor its conservation can be ac- All classical theories proposed that natural selection acted on counted for by the random fixation of neutral or nearly neutral the ‘‘phenotype’’ [called the ‘‘classical phenotype’’ by Bernardi single-nucleotide changes (i.e., the vast majority of nucleotide and Bernardi (14), to distinguish it from the ‘‘genome pheno- substitutions) or by a biased gene conversion process occurring at type’’ presented below]. -
Molecular Evolution 1
Molecular Evolution 1. Evolutionary Tree Reconstruction 2. Two Hypotheses for Human Evolution 3. Did we evolve from Neanderthals? 4. Distance-Based Phylogeny 5. Neighbor Joining Algorithm 6. Additive Phylogeny 7. Least Squares Distance Phylogeny 8. UPGMA 9. Character-Based Phylogeny 10. Small Parsimony Problem 11. Fitch and Sankoff Algorithms 12. Large Parsimony Problem 13. Nearest Neighbor Interchange 14. Evolution of Human Repeats 15. Minimum Spanning Trees Section 1: Evolutionary Tree Reconstruction Early Evolutionary Studies • Anatomical features were the dominant criteria used to derive evolutionary relationships between species since Darwin till early 1960s. • The evolutionary relationships derived from these relatively subjective observations were often inconclusive. Some of them were later proven incorrect. DNA Analysis: The Giant Panda Riddle • For roughly 100 years, scientists were unable to figure out to which family the giant panda should belong. • Giant pandas look like bears but have features that are unusual for bears and typical for raccoons, e.g. they do not hibernate. • In 1985, Steven O’Brien and colleagues solved the giant panda classification problem using DNA sequences and algorithms. Evolutionary Tree of Bears and Raccoons Evolutionary Trees: DNA-Based Approach • 40 years ago: Emile Zuckerkandl and Linus Pauling brought reconstructing evolutionary relationships with DNA into the spotlight. • In the first few years after Zuckerkandl and Emile Zuckerkandl Pauling proposed using DNA for evolutionary studies, the possibility -
National Institute of Genetics Japan
ISSN 0077-4995 NATIONAL INSTITUTE OF GENETICS JAPAN ANNUAL REPORT No. 40 1989 Published by THE NATIONAL INSTITUTE OF GENETICS Mi.ima, Sizuoka-ken, Japan 1990 Annual Report of the National Institute of Genetics No. 40, 1989 Published by The National Institute of Genetics, Japan 1990 CONTENTS General statement .........................................I Staff 3 Council and Advisory Committee. ................................ 6 Association for propagation of the knowledge of genetics 8 Projects of research for 1989 9 Research activities in 1989 14 I. Molecular Genetics Promoter selectivity of Escherichia coli RNA polymerase, I. Effect of base substitutions in promoter - 35 region on the promoter strength. KOBAYASHI, M., NAGATA, K. and ISHIHAMA, A. ... 14 The promoter selectivity of Escherichia coli RNA polymerase, II. Random screening of promoters and classification based on the promoter strength. KUBOTA, M., YAMAZAKI, Y. and ISHIHAMA, A. 15 Promoter selectivity of Escherichia coli RNA polymerase, III. Structural and functional modulations of RNA polymerase during growth phase transition. OZAKI, M., FUJITA, N., WADA, A. and ISHIHAMA, A. ..... 16 Structural modulation of ribosomes during growth phase transition of Escherichia coli. WADA, A., YAMAZAKI, Y., FUJITA, N. and ISHIHAMA, A. 17 The molecular anatomy of Escherichia coli RNA polymerase: Func tional mapping of the a subunit. IGARASHI, K., HAYWARD, R. S., FUJITA, N., YAMAGISHI, M. and ISHIHAMA, A. 18 Promoter selectivity of Micrococcus luteus RNA polymerase: Identification and characterization of the major sigma factor. NAKAYAMA, M., FUJITA, N., OSAWA, S. and ISHIHAMA, A..... 19 Molecular mechanisms of transcription and replication of phage Qfi: Cloning, sequencing and mapping of host factor. KAJI- TANI, M. and ISHIHAMA, A. -
2012Zuckerkandl.Pdf
J Mol Evol DOI 10.1007/s00239-012-9511-6 Fifty-Year Old and Still Ticking.... An Interview with Emile Zuckerkandl on the 50th Anniversary of the Molecular Clock Giacomo Bernardi Received: 24 May 2012 / Accepted: 12 June 2012 Ó Springer Science+Business Media, LLC 2012 Abstract In 1962, a young post-doctoral fellow and a population demographies rely on its principles. Thus the prominent Nobel Prize winner, Emile Zuckerkandl and consequences of the molecular clock are far-reaching. Linus Pauling, published a seminal paper that described the Fifty years after the original publication, I was fortunate relationship between the average number of aminoacid enough to interview Emile Zuckerkandl. We shared replacements and divergence time, known as the molecular thoughts on his life and the historical events that led to the clock (Zuckerkandl and Pauling 1962). Fifty years after the discovery of the molecular clock. Jane and Emile wel- original publication, I was fortunate enough to interview comed me into their elegant home in Palo Alto (Fig. 1). Emile Zuckerkandl. We shared thoughts on his life and the Emile recounted the events leading to the discovery, while historical events that led to the discovery of the molecular Jane peppered the conversation with insights and an clock. incredibly acute memory. Below are excerpts of this conversation. Keywords Molecular clock Emile Zuckerkandl Giacomo Bernardi: Dear Emile, thank you so much for Á Á Linus Pauling giving me the opportunity to ask you questions about your scientific and private life. As you know, 2012 marks the 50th anniversary of the first paper on molecular clocks that Interview you wrote with Linus Pauling (Zuckerkandl and Pauling 1962).