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.


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

@OfficialSMBE Feed

MBE | Most Read

Molecular Biology and Evolution

Wed, 22 Nov 2017 00:00:00 GMT

Wed, 22 Nov 2017 00:00:00 GMT

Wed, 22 Nov 2017 00:00:00 GMT

Exploring the Adaptation Extremes of Human High Altitude Sickness and Fitness

Wed, 22 Nov 2017 00:00:00 GMT

Tibetans, Ethiopians, and Peruvians.

Wed, 22 Nov 2017 00:00:00 GMT

Thu, 16 Nov 2017 00:00:00 GMT

Wed, 04 Oct 2017 00:00:00 GMT

Tue, 03 Oct 2017 00:00:00 GMT

Thu, 28 Sep 2017 00:00:00 GMT

Wed, 27 Sep 2017 00:00:00 GMT

Tue, 26 Sep 2017 00:00:00 GMT

Tue, 26 Sep 2017 00:00:00 GMT

Species Tree Root Inference from Gene Duplication Events

Tue, 26 Sep 2017 00:00:00 GMT

Tue, 26 Sep 2017 00:00:00 GMT

Mon, 25 Sep 2017 00:00:00 GMT

Mon, 25 Sep 2017 00:00:00 GMT

Tue, 19 Sep 2017 00:00:00 GMT

DNA Sequence Polymorphism Analysis of Large Data Sets

Mon, 18 Sep 2017 00:00:00 GMT

1) modules for reading and analyzing data from genomic partitioning methods, such as RADseq or hybrid enrichment approaches, 2) faster methods scalable for high-throughput sequencing data, and 3) summary statistics for the analysis of multi-locus population genetics data. Furthermore, DnaSP 6 includes novel modules to perform single- and multi-locus coalescent simulations under a wide range of demographic scenarios. The DnaSP 6 program, with extensive documentation, is freely available at">">

Thu, 14 Sep 2017 00:00:00 GMT

Thu, 14 Sep 2017 00:00:00 GMT

Tue, 12 Sep 2017 00:00:00 GMT

Mon, 11 Sep 2017 00:00:00 GMT

selective sweeps wherein large shifts in the allele frequencies occur at a few loci and evolution via small changes in the allele frequencies at many loci. Although the first process has been thoroughly investigated within the framework of population genetics, the latter is based on quantitative genetics and is much less understood. Here we summarize results from our recent theoretical studies of a quantitative genetic model of polygenic adaptation that makes explicit reference to population genetics to bridge the gap between the two frameworks. Our key results are that polygenic adaptation may be a rapid process and can proceed via subtle or dramatic changes in the allele frequency depending on the sizes of the phenotypic effects relative to a threshold value. We also discuss how the signals of polygenic selection may be detected in the genome. Although powerful methods are available to identify signatures of selective sweeps at loci controlling quantitative traits, the development of statistical tests for detecting small shifts of allele frequencies at quantitative trait loci is still in its infancy.

Sat, 09 Sep 2017 00:00:00 GMT

Tue, 05 Sep 2017 00:00:00 GMT

Hidden Genes Uncovered and the Rates versus Traits Paradox in Birds

Tue, 05 Sep 2017 00:00:00 GMT

A Package for Phylogenetic Networks

Mon, 04 Sep 2017 00:00:00 GMT

Wed, 30 Aug 2017 00:00:00 GMT

Rapid Adaptation in a Polygenic Trait Proceeded Exclusively through Expression Differentiation

Wed, 30 Aug 2017 00:00:00 GMT

Thu, 24 Aug 2017 00:00:00 GMT

Wed, 05 Jul 2017 00:00:00 GMT

GBE | Most Read

Genome Biology & Evolution

Emergence and Spread of Epidemic Multidrug-Resistant Pseudomonas aeruginosa

Wed, 29 Nov 2017 00:00:00 GMT

Pseudomonas aeruginosa (P. aeruginosa) is one of the most common nosocomial pathogens worldwide. Although the emergence of multidrug-resistant (MDR) P. aeruginosa is a critical problem in medical practice, the key features involved in the emergence and spread of MDR P. aeruginosa remain unknown. This study utilized whole genome sequence (WGS) analyses to define the population structure of 185 P. aeruginosa clinical isolates from several countries. Of these 185 isolates, 136 were categorized into sequence type (ST) 235, one of the most common types worldwide. Phylogenetic analysis showed that these isolates fell within seven subclades. Each subclade harbors characteristic drug resistance genes and a characteristic genetic background confined to a geographic location, suggesting that clonal expansion following antibiotic exposure is the driving force in generating the population structure of MDR P. aeruginosa. WGS analyses also showed that the substitution rate was markedly higher in ST235 MDR P. aeruginosa than in other strains. Notably, almost all ST235 isolates harbor the specific type IV secretion system and very few or none harbor the CRISPR/CAS system. These findings may help explain the mechanism underlying the emergence and spread of ST235 P. aeruginosa as the predominant MDR lineage.

Horizontal Acquisition and Transcriptional Integration of Novel Genes in Mosquito-Associated Spiroplasma

Tue, 21 Nov 2017 00:00:00 GMT

Genetic differentiation among symbiotic bacteria is important in shaping biodiversity. The genus Spiroplasma contains species occupying diverse niches and is a model system for symbiont evolution. Previous studies have established that two mosquito-associated species have diverged extensively in their carbohydrate metabolism genes despite having a close phylogenetic relationship. Notably, although the commensal Spiroplasma diminutum lacks identifiable pathogenicity factors, the pathogenic Spiroplasma taiwanense was found to have acquired a virulence factor glpO and its associated genes through horizontal transfer. However, it is unclear if these acquired genes have been integrated into the regulatory network. In this study, we inferred the gene content evolution in these bacteria, as well as examined their transcriptomes in response to glucose availability. The results indicated that both species have many more gene acquisitions from the Mycoides-Entomoplasmataceae clade, which contains several important pathogens of ruminants, than previously thought. Moreover, several acquired genes have higher expression levels than the vertically inherited homologs, indicating possible functional replacement. Finally, the virulence factor and its functionally linked genes in S. taiwanense were up-regulated in response to glucose starvation, suggesting that these acquired genes are under expression regulation and the pathogenicity may be a stress response. In summary, although differential gene losses are a major process for symbiont divergence, gene gains are critical in counteracting genome degradation and driving diversification among facultative symbionts.

The Diversity of REcent and Ancient huMan (DREAM): A New Microarray for Genetic Anthropology and Genealogy, Forensics, and Personalized Medicine

Mon, 20 Nov 2017 00:00:00 GMT

The human population displays wide variety in demographic history, ancestry, content of DNA derived from hominins or ancient populations, adaptation, traits, copy number variation, drug response, and more. These polymorphisms are of broad interest to population geneticists, forensics investigators, and medical professionals. Historically, much of that knowledge was gained from population survey projects. Although many commercial arrays exist for genome-wide single-nucleotide polymorphism genotyping, their design specifications are limited and they do not allow a full exploration of biodiversity. We thereby aimed to design the Diversity of REcent and Ancient huMan (DREAM)—an all-inclusive microarray that would allow both identification of known associations and exploration of standing questions in genetic anthropology, forensics, and personalized medicine. DREAM includes probes to interrogate ancestry informative markers obtained from over 450 human populations, over 200 ancient genomes, and 10 archaic hominins. DREAM can identify 94% and 61% of all known Y and mitochondrial haplogroups, respectively, and was vetted to avoid interrogation of clinically relevant markers. To demonstrate its capabilities, we compared its FST distributions with those of the 1000 Genomes Project and commercial arrays. Although all arrays yielded similarly shaped (inverse J) FST distributions, DREAM’s autosomal and X-chromosomal distributions had the highest mean FST, attesting to its ability to discern subpopulations. DREAM performances are further illustrated in biogeographical, identical by descent, and copy number variation analyses. In summary, with approximately 800,000 markers spanning nearly 2,000 genes, DREAM is a useful tool for genetic anthropology, forensic, and personalized medicine studies.

Structure-Related Differences between Cytochrome Oxidase I Proteins in a Stable Heteroplasmic Mitochondrial System

Tue, 14 Nov 2017 00:00:00 GMT

Many bivalve species have two types of mitochondrial DNA passed independently through the female line (F genome) and male line (M genome). Here we study the cytochrome oxidase I protein in such bivalve species and provide evidence for differences between the F and M proteins in amino acid property values, particularly relating to hydrophobicity and helicity. The magnitude of these differences varies between different regions of the protein and the change from the ancestor is most marked in the M protein. The observed changes occur in parallel and in the same direction in the different species studied. Two possible causes are considered, first relaxation of purifying selection with drift and second positive selection. These may operate in different ways in different regions of the protein. Many different amino acid substitutions contribute in a small way to the observed variation, but substitutions involving alanine and serine have a quantitatively large effect. Some of these substitutions are potential targets for phosphorylation and some are close to residues of functional importance in the catalytic mechanism. We propose that the observed changes in the F and M proteins might contribute to functional differences between them relating to ATP production and mitochondrial membrane potential with implications for sperm function.

The Novel Evolution of the Sperm Whale Genome

Wed, 13 Sep 2017 00:00:00 GMT

The sperm whale, made famous by Moby Dick, is one of the most fascinating of all ocean-dwelling species given their unique life history, novel physiological adaptations to hunting squid at extreme ocean depths, and their position as one of the earliest branching toothed whales (Odontoceti). We assembled the sperm whale (Physeter macrocephalus) genome and resequenced individuals from multiple ocean basins to identify new candidate genes for adaptation to an aquatic environment and infer demographic history. Genes crucial for skin integrity appeared to be particularly important in both the sperm whale and other cetaceans. We also find sperm whales experienced a steep population decline during the early Pleistocene epoch. These genomic data add new comparative insight into the evolution of whales.