Name: SAITOU Naruya (Laboratory: Population Genetics)
Title: Phylogeny, human evolution, and CNSs: three main areas I studied for almost
45 years of my research

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When I was sophomore in the University of Tokyo, 19 years old in 1976, I came to know the neutral
theory of evolution by reading a Japanese review article written by Dr. Kimura Motoo (ref. 1). I
immediately fell in love with this theory, and started to learn population genetics theory andmolecular evolution. When I was senior at Department of Biology, majoring in physicalanthropology, I decided to study genetical anthropology under Professor Omoto Keiichi. I carefully
read one paper on molecular phylogeny written by Cavalli-Sforza and Edwards in 1967 (ref. 2). Iwas asked to explain this paper by Omoto laboratory members including Dr. Horai Satoshi, wholater joined NIG. This experience gave me a great hint when I developed the neighbor-joining
method (ref. 3).
In my master course, I estimated the age of mutants found in Philippine Negrito populations
by Professor Omoto’s group, applying a branching process. This was my master thesis, but my rst
academic paper was estimation of migration pattern in Japan using surname data collected throughtelephone books. This paper, written in Japanese, was published in 1983 (ref. 4), when I was in
Houston, Texas. After visiting Negrito villages in the Philippines from December 1981 to January
1982, I joined Professor Masatoshi Nei’s Laboratory in University of Texas, Houston in the summerof 1982. Nei Laboratory was a stronghold of the neutral theory at that time. Drs. Wen-Hsiung Liand Ranajit Chakaraborty were faculty members, Drs. Gojobori Takashi and Chung-I Wu werepostdoc, and Drs. Tajima Fumio and Dan Graur were graduate students.
During four years in Houston, I worked pretty hard, and my Ph.D thesis consisted of threechapters including proposal of the neighbor-joining method. I also analyzed in uenza A virus genesequence data, and published two papers, but did not combine these with my Ph.D. thesis. I returned
to Japan in fall of 1986, and did two years of JSPS postdoctoral fellow. During that period, I visited
ethnic minorities in Hainan Island, China with Professor Omoto. I then became an assistantprofessor at Department of Anthropology, Faculty of Science, the University of Tokyo in 1989. I
visited indigenous peoples in Taiwan with Dr. Horai Satoshi in 1990 and 1991.
Professor Gojobori Takashi, who became head of DDBJ at NIG at that time, asked me tojoin DDBJ. I was very pleased with this offer, and joined NIG as associate professor at Division ofEvolutionary Genetics on January 16th, 1991. Therefore, I have been at NIG for slightly more than
31 years, though I worked for DDBJ until 2008. During this period, I published 233 papers andbooks. Among them, 23 are single-authored ones (mainly review articles) and 9 are rst-authoredones. I am corresponding author of 45 papers that were rst-authored by my former students andpostdocs.
Papers that were mainly produced by SAITOU Lab members are very heterogenous. Forexample, Satoshi OOta, my rst Ph.D. student, estimated the phylogeny of muscle tissues (ref. 5).
This work was mentioned by Nick Lane’s book (ref. 6) for general audience. One of my nephews
who went to law school read its Japanese translation, and he was surprised by nding my name inthat book. Though this paper was cited only 93 times according to Google Scholar, I am happy withthis episode.
When I moved to NIG, I just started to analyze human ABO blood group gene sequences. I
contacted Dr. Fumiichiro Yamamoto, who determined the nucleotide sequences of human ABO
genes for collaboration. I suggested him to determine non-human ABO blood group sequences, andhe did. Therefore, when Takashi Kitano, my second Ph.D student, joined my laboratory in 1996, I
suggested him to study orthologs of human Rh blood group genes and its paralogous genes. Wecollected bone marrow samples from mice, rat, and crab-eating macaque, and determined Rh andRh50 gene sequences (ref. 7).
In 2000, determination of the draft human genome sequences was announced. Area ofmolecular evolution should also move to evolutionary genomics. I thus started Ape Genome
Project, nicknamed Silver, for atomic symbol of silver is Ag. With the help of Dr. Fujiyama Asao,
Dr. Kim Chun-Gong produced gorilla fosmid library (ref. 8). My laboratory was also involved inthe international chimpanzee chromosome 22 sequencing project headed by Dr. Sakaki Yoshiyuki.
However, I was also interested in gene hunting, and focused on ear wax gene. Ear wax has along history of research in Japan. Dr. Takahashi Aya, who just received Ph.D. in University ofChicago under Professor Chung-I Wu, joined my lab as a post-doc in 2000, and I suggested her tohunt for ear wax gene. In one day in 2002, I found a surprising news in a Japanese weekly
magazine; Nagasaki University group discovered the ear wax gene. I was shocked, but found thecorresponding paper and was relieved to know that they only narrowed down the chromosome
region for the ear wax gene. I quickly contacted Professor Niikawa Norio at Nagasaki University
Medical School, and my laboratory joined the ear-wax hunting team. Eventually, four years later,
ABCC11 was found to be the gene for ear wax (ref. 9). My former student Ishibashi Minaka, as
well as Takahashi Aya and myself, were coauthors of this paper.
When Takahashi (now Ueda) Mahoko joined my lab as the 11th Ph.D. student in 2005, Isuggested her to study CNSs (Conserved Noncoding Sequences) among primates and rodents.
Matsunami Masatoshi, my 12th Ph.D. student, also studied CNSs, but he rst focused on Hox geneclusters, and his paper (ref. 10) was the rst CNS related paper published from Saitou Laboratory.
Later, three students from Nigeria (Isaac Babarinde), Sri Lanka (Nilmini Hettiarachchi), and Iran(Mahmoudi Saber Morteza), as well as Inoue Jun, who constructed dbCNS (http://yamasati.nig.ac.jp/dbcns/), also studied CNS evolution.
Meanwhile, Timothy A. Jinam joined my laboratory as Ph.D. student in 2008. He alreadyhad experience of analyzing genome-wide SNP data of modern human populations in Malaysia. I
thus suggested him to study similar data of Japanese populations. He has been very productive, andafter doing postdoc at Division of Human Genetics, NIG, he became assistant professor of mylaboratory after Dr. Sumiyama Kenta moved out to Riken Center for Biosystems Dynamics
Research. Tim is an important member of our “Yaponesia Genome Project” (http://www.yaponesian.jp).
Kanzawa Hideaki became Ph.D student of my laboratory in 2009, and he wanted to study
ancient DNA. I managed to nd some grant from Indus Project at Research institute for Humanity
and Nature to set up a primitive aDNA working space in my laboratory, and he eventually obtained
partial genome sequence of Jomon people, and we published a paper in 2016 (ref. 11).
In 2020 A.D. (or in my year, year 0020), I started a new online journal “iDarwin” (http://idarwin.org) on the birthday of Charles Darwin (ref. 12). At this moment, not many articles are
published in this journal, however, I do hope that this journal will become an important asset forevolutionary studies.

Referencesfifi

パfifiRef. 1. 木村資生 (1976) 分子進化論および集団遺伝学における中立説の立場. 科学, 46巻, 528-535頁.
Ref. 2. Cavalli-Sforza L. L. and Edwards A. (1967) Phylogenetic analysis. Models and estimation procedures.
American Journal of Human Genetics, vol. 19, pp. 233–257.
Ref. 3. Saitou N. and Nei M. (1987) The neighbor-joining method: A new method for reconstructing phylogenetictrees. Molecular and Biological Evolution, vol. 4, pp. 406–425.
Ref. 4. 斎藤成也 (1983) 苗字資料による国内の移住 ターン推定の試み. 人類学雑誌, 第91巻3号, 309-322頁.
Ref. 5. OOta S. and Saitou N. (1999) Phylogenetic relationship of muscle tissues deduced from superimposition ofgene trees. Molecular and Biological Evolution, vol. 16, pp. 856–867.
Ref. 6. Lane N. (2009) Life ascending — The ten great inventions of evolution. Pro le Books Ltd. {日本語訳：ニック・レーン著、斉藤隆央訳 (2010) 生命の跳躍‒進化の10大発明‒. みすず書房｝

Ref. 7. Kitano T., Sumiyama K., Shiroishi T., and Saitou N. (1998) Conserved evolution of the Rh50 gene compared
to its homologous Rh blood group gene. Biochemical and Biophysical Research Communications, vol. 249, pp.
78-85.
Ref. 8. Kim C.-G., Fujiyama A., and Saitou N. (2003) Construction of a gorilla fosmid library and its PCR screeningsystem. Genomics, vol. 82, pp. 571-574.
Ref. 9. Yoshiura K. et al. (2006) A SNP in the ABCC11 gene is the determinant of human earwax type. NatureGenetics, vol. 38, pp. 324-330.
Ref. 10. Matsunami M., Sumiyama K., and Saitou N. (2010) Evolution of conserved non-coding sequences within thevertebrate Hox clusters through the two-round whole genome duplications revealed by phylogenetic footprinting
analysis. Journal of Molecular Evolution, vol. 71, pp. 427-436.
Ref. 11. Kanzawa-Kiriyama H. et al. (2016) A partial nuclear genome of the Jomons who lived 3000 years ago inFukushima, Japan. Journal of Human Genetics (Advance online).
Ref. 12. Saitou N. (0020) iDarwin: Quixotic idea? iDarwin, vol. 0, pp. 1-6.

English seminar: Yes