The Masatoshi Nei Lecture

SMBE members attending the 1999 Business Meeting in Brisbane, Australia, voted to establish the Masatoshi Nei Lecture to be delivered by the President at annual Society meetings.

Masatoshi Nei (根井正利 Nei Masatoshi) is Evan Pugh Professor of Biology at Pennsylvania State University and Director of the Institute of Molecular Evolutionary Genetics since 1990. He was born in 1931 in Miyazaki Prefecture, on Kyūshū Island, Japan. He was associate professor and professor of biology at Brown University from 1969 to 1972 and professor of population genetics at the Center for Demographic and Population Genetics, University of Texas at Houston, from 1972 to 1990. He is a theoretical population geneticist and evolutionary biologist. Acting alone or working with his students, he has continuously developed new statistical theories of molecular evolution taking into account frontier knowledge of molecular biology. He has also made several conceptual developments of evolutionary theory.

Theoretical Studies

He was the first to show mathematically that in the presence of gene interaction, natural selection always tends to enhance the linkage intensity between genetic loci or maintain the same linkage relationship. He then observed that the average recombination value per genome is generally lower in higher organisms than in lower organisms and attributed this observation to his finding of linkage modification by natural selection. Recent molecular data indicate that many sets of interacting genes such as Hox genes, immunoglobulin genes, and histone genes often exist as gene clusters for a long evolutionary time. This observation can also be explained by his principle of maintenance of linkage of interacting genes. He also showed that, unlike R. A. Fisher’s argument, deleterious mutations can accumulate rather quickly on the Y chromosome or duplicate genes in finite populations. In 1969, considering the rates of amino acid substitution, gene duplication, and gene inactivation, he predicted that higher organisms contain a large number of duplicate genes and nonfunctional genes (now called pseudogenes). This prediction was ignored for many years but later vindicated when many multigene families and pseudogenes were discovered in the 1980s. His notable contribution in the early 1970s is the proposal of a new measure of genetic distance (Nei’s distance) between populations and its use for studying evolutionary relationships of populations or closely related species. Later, he developed another distance measure called DA, which is appropriate for finding the topology of a phylogenetic tree. He also developed statistics of measuring the extent of population differentiation for any types of mating system using GST measure. In 1975, he and collaborators presented a mathematical formulation of population bottleneck effects and clarified the genetic meaning of bottleneck effects. In 1979, he developed a mathematical theory for studying genetic variation in terms of restriction enzymes.[10] In collaboration with Takeo Maruyama and Chung-I Wu, he also developed a theory of evolution of reproductive isolation using various models of incompatibility of genes between two isolated populations.

Protein polymorphism and neutral theory

In the early 1960s and 1970s, there was a great controversy over the mechanism of protein evolution and the maintenance of protein polymorphism. Nei and his students developed various statistical methods for testing the neutral theory of evolution by using polymorphism data. Their analysis of the allele frequency distribution, the relationship between average heterozygosity and protein divergence between species, etc., could not reject the null hypothesis of neutral evolution though a large amount of data for various genes from diverse groups of species were examined. The only exception was the major histocompatibility complex (MHC) loci, which show an extraordinarily high degree of polymorphism. He also showed that pseudogenes may represent a paradigm of neutral evolution without any selection.

Human evolution

Using his genetic distance theory, he and A. K. Roychoudhury showed that the genetic variation between Europeans, Asians, and Africans is only about 11 percent of the total genetic variation of the human population, which was in agreement with the results published by R. C. Lewontin in the same year. Nei and Roychoudhury then estimated that Europeans and Asians diverged about 55,000 years ago and these two populations diverged from Africans about 115,000 years ago. This conclusion was supported by many later studies using larger numbers of genes and populations, and the estimates are still widely used. This study was a forerunner of the out of Africa theory of human origin by Allan Wilson.

Molecular phylogenetics

Around 1980, Nei and his students initiated a study of inference of phylogenetic trees based on distance data. In 1985 they developed a statistical method for testing the accuracy of a phylogenetic tree by examining the statistical significance of interior branch lengths. They then developed the neighbor-joining and minimum-evolution methods of tree inference. They also developed statistical methods for estimating evolutionary times from molecular phylogenies. In collaboration with Sudhir Kumar and Koichiro Tamura, he developed a widely used computer program package for phylogenetic analysis called MEGA.

MHC loci and positive Darwinian selection

Nei’s group invented a statistical method for detecting positive Darwinian selection by comparing the numbers of synonymous nucleotide substitutions and nonsynonymous nucleotide substitutions. Applying this method, they showed that the exceptionally high degree of sequence polymorphism at MHC loci is caused by overdominant selection.[19] Although various statistical methods for this test have been later developed, their original methods are still widely used. He maintains that the Bayesian method of inferring positively selected amino acid sites tends to give false-positives and experimental tests are necessary for confirmation of these sites.

Birth-and-death evolution and neomutationism

Nei and his students studied the evolutionary patterns of a large number of multigene families and showed that they generally evolve following the model of a birth-and-death process.In some gene families this process is very fast and caused by random events of gene duplication and gene deletion and generates genomic drift of gene copy number. Nei has long maintained the view that the driving force of evolution is mutation including any types of genetic changes and natural selection is merely a force eliminating less fit genotypes (neomutationism). He conducted statistical analyses of the evolution of genes controlling phenotypic characters such as olfactory reception and obtained evidence supporting his neomutationism.

New journal, new society, and students

He founded the journal Molecular Biology and Evolution in 1983 and the Society for Molecular Biology and Evolution in 1993, together with Walter M. Fitch. He also trained many graduate students and postdoctorals who have become leading figures in molecular evolution including Margaret Kidwell, Wen-Hsiung Li, Ranajit Chakraborty, Shozo Yokoyama, Aravinda Chakravarti, Dan Graur, Fumio Tajima, Chung-I Wu, Naoyuki Takahata, Takashi Gojobori, Pekka Pamilo, Austin Hughes, Andrey Rzhetsky, Jianzhi (George) Zhang, and Sudhir Kumar.

Recognition

Year Title
1977 Japan Society of Human Genetics Award
1990 Fellow, American Academy of Arts and Sciences
1990 Kihara Prize, Genetics Society of Japan
1997 Member, National Academy of Sciences, USA
2002 International Prize for Biology, Japan Society of the Promotion of Sciences
2003 Barbara Bowman Award, Texas Geneticist Society
2006 Thomas Hunt Morgan Medal, Genetics Society of America

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