Impact Objectives• Study human population genetics and molecular evolution of various
genome sequences• Explore the genomic and biological basis for the difference in selfconsciousness between humans and primates• Uncover the origins and formation of the Yaponesian people to understandmore about modern Japan

Sequencing ancient history
Professor Naruya Saitou talks about his research into genomics and the history of the Yaponesian people
which straddles archaeology, linguists and genomics
as an Associate Professor. I was promoted
to Professor of population genetics in 2002,
which is my current position. I continue
to study human population genetics andmolecular evolution of various genome
sequences.
Professor Naruya
SaitouDr Timothy A Jinam

How did you come to be involved in thisfield of research?
NS: I received my BSc and MSc majoring inphysical anthropology from the Universityof Tokyo in 1979 and 1981, respectively. I
was already seeking to fuse natural scienceand social science from that time. However,
I was fascinated by the neutral theory ofmolecular evolution, and joined Professor
Masatoshi Nei’s group at Houston, USA,as a PhD student from 1982 to 1986. One
chapter of my PhD thesis was a proposal
for the Neighbor-Joining method for theconstruction of phylogenetic trees. After
receiving my PhD, I returned to Japan andagain studied physical anthropology between
1987-1991 at the University of Tokyo, initiallyas post-doctorate student, and later asassistant professor. I visited southern andnorthern China during this period to study
various ethnic minority groups there. In
1991, I joined DDBJ (DNA Data Bank ofJapan) at the National Institute of Genetics
56 www.impact.pub

Can you talk a little about how your research
integrates biological studies with humanity
and social science studies?
NS: Sciences are divided into many research
fields. However, natural phenomena arein fact all connected, and in my view, allsciences, irrespective in natural sciences,
social sciences or humanities, should beunited. Fortunately, I have a broad interestin many biological and human activities,
partially because of my anthropology
background. My first original paper wason surname distribution in Japan, and I
used various statistical methods to analyse
surnames using computer programs. I
believe all data, either DNA sequences,linguistic data, or archaeological data, can beanalysed in a similar way.
What types of obstacles do you face in yourresearch?
NS: Genome sequencing was very costly
for a long time, so I had difficulty securing
appropriate funding for sequencing variousorganisms. I once collaborated with a RIKEN
group who were interested in sequencing
chimpanzee genomes. Although only 1 percent of the whole genome was determined,
our paper was published in Nature in 2004.
Another challenge is collaboration witharchaeologists and linguists. Fortunately, I
had close contact with some linguists for 30
years, and nowadays I am often invited tolinguistics conferences. Generally, linguists
are more open minded than archaeologists,
who are mostly interested in archaeologicalevidence. We try our best to integrate thesedifferent research fields with genomics.
Dr Timothy A Jinam, Assistant Professor
in my laboratory, is playing a major role inanalysing human genome data in our group.
You have a particular interest in primate andhuman evolution. What are the goals andaims for your research?
NS: Since my childhood, I have beenfascinated by the concept of ‘self’ and selfconsciousness. Monkeys and apes also havetheir self-consciousness, but human selfconsciousness seems to be clearly different
from primates. I hope to find the genomic
and biological basis of this difference interms of self-consciousness. This is myultimate goal. lThe origins of the Japanese
Researchers at the Population Genetics Laboratory in Mishima are uncovering the nature andformation of the Yaponesian people’s ancient past and trying to understand the origins of those thatmake up modern JapanTo understand our origins and history is afundamental urge for all people. For as long as
history has been recorded, people have createdstories and myths about their origins andancestry. This has not changed to this day. The
difference now, however, is that we have theresources and technical skills to map out tensof thousands of years of history. The ebb andflow of human migration across planet Earthcan be probed with advanced archaeology,
linguistics, anthropology and genomics.
Together, these can provide a convincing
picture of the various divergences andconvergences of different human populations
across vast areas. In particular, it is possible
to better understand how, why and where aparticular group or society arose.
Whilst each of these fields have contributed
towards this grand picture of human evolution
and migration, few attempts to synthesise allthese approaches together have been made.
Indeed, there is often a certain antagonism
between the different areas of expertise.
Naturally, it is practically impossible to be
an expert in all the areas. However, there
is certainly room for researchers looking
to bridge the gaps. In fact, this is essential
if a full and accurate picture is to emerge,
because a conclusion drawn by one of thedisciplines alone would be incomplete without
information from one of the others. Therefore,
it is extremely important that there is work
carried out that links these diverse fields.

A FOCUS ON DNA
Professor Naruya Saitou of the Population
Genetics Laboratory at the National Instituteof Genetics in Mishima has dedicated hiscareer to this synthesis of disciplines. Having
initially studied physical anthropology, hecompleted his PhD in genetics. Since thenhe has worked in anthropology but primarily
in the context of population genetics andmolecular evolution. Saitou has worked inmany different areas and with many different
fields since then.
His most recent work has been a focus onhuman genome-wide SNP data and using thisto understand the history and evolution of theJapanese Archipelago. ‘I have been interested
in the molecular basis for macroscopic
morphological characters, and am convincedthat evolutionarily-conserved noncoding
sequences (CNSs) are clues given that themajority of these CNSs are now known to beinvolved in gene expression,’ highlights Saitou.
‘Another different aspect in my research topic
is development of new methods for molecular
evolutionary studies.’
UNITING DISPARATE DISCIPLINES
Saitou has been involved in a myriad ofprojects over a long career. However,
his focus in recent times has been onunderstanding the origins and formation of
the Yaponesian people. This broad term wascoined by writer Toshio Shimao in 1960s
to encompass the diverse peoples of theJapanese Archipelago over its many thousandsof years of inhabitation. This vast project has
encompassed many different branches suchas genomics, anthropology, archaeology andlinguistics. At the same time, he and his teamare experts on genomic comparison and are
constantly developing new ways to analyse andunderstand genomic data.
Whilst this project has been a part of Saitou’s
interests for many years, it is only in the last
decade or so that genome sequencing has
made the scale of his ambitions possible.
‘Although we have been sequencing genomes
for several decades now, the last 10 years has
seen a steep drop in the cost of this process,’he comments. ‘This has made large-scale
genetic studies of both modern and ancientgenomes a real possibility.’ In turn, thisopens new avenues towards understanding
a population’s likely origins and potential
insights into migratory phenomena that may
have occurred at different times.
TWO GREAT WAVES
Saitou’s work on the genetic diversity of
the Japanese Archipelago has been able topinpoint two key migratory events in thehistory of Japan. The first inhabitants of theislands were the Jomon peoples - huntergathers who dominated the islands until
around three thousand years ago. Saitouand his team have found a relatively lowpercentage of their DNA in the populationsof modern Japan. However, the similarity
www.impact.pub 57

Project Insights
FUNDINGMEXT Japan Grant-in-Aid for Scientific
Research on Innovative Areas, Japan InterUniversity Research Institute Corporation
Organizations Inter-Organization
Interdisciplinary Research Project, Genesis
Healthcare-NIG Collaborative Research,
MEXT Japan Grant-in-Aid for Scientific
Research (A)is much higher with the inhabitants ofHokkaido and Okinawa - the northernmostand southernmost regions. The inhabitantsof these islands - the Ainu and Ryukyuans- have long assumed to be different frommainland Japanese populations. This was due
to morphological and linguistic differences
between the populations.
The rest of the genetic make-up of theJapanese population is derived from asecond wave of migration - the Yayoi. Thesegenes. But genetics also play a key role inaltering the likelihood of a huge range of otherdiseases.’ Everything from heart disease to gut
diseases and neurological issues all have astrong genetic component. However, whilst a
genetic link has been established and, in somecases, specific genes identified, in many morecases the nature of the genetic link is unclear.
‘Therefore, sequencing and analysing moregenomes will help provide more information
about the links between genetics and health,’
he continues. ‘In particular, it has long been

Sequencing and analysing more genomes will help
provide more information about the links between
genetics and healthmigrants arrived from somewhere on theEast Asian mainland and brought agriculture
to the archipelago. ‘The exact timing of the
migration is disputed; however, it appears
to have started between 3 and 2.5 thousandyears ago,’ confirms Saitou. ‘In addition toagriculture, they also brought a range of novel
technologies as well as a new language.’ Heexplains that their DNA lineage is by far themost dominant in all Japanese populations.
The DNA evidence, therefore, supports andcompliments the archaeological and linguistic
evidence that suggests these two major
migratory events in Japanese history.
MODERN USES OF ANCIENT HISTORY
The results of Saitou’s Yaponesian project
are already proving interesting and helping
to uncover Japan’s ancient past. However,as more genomes are sequenced and thedifferent genotypes of people in Japan are
better understood, there will be other benefits
too. Obtaining these data can provide valuable
information as to likely genetic components
in health and disease. ‘There is a complex
and intricate relationship between the exact
genetics of a person and their likelihood ofdeveloping certain diseases,’ says Saitou.
‘Cancers are perhaps the most obvious
example, deriving from mutations in particular
58 www.impact.pub

suspected that the large parts of the humangenome that are non-coding have a key rolein this process.’ These are also the regions of
the genome that Saitou is interested to carryout his evolutionary studies as he is convincedthat they provide the region of key changes
and the origins of vast genetic diversity.
Sequencing genomes is merely the firststep towards understanding the genetic
information. In order to derive anything of use
from the sequencing process, sophisticatedanalyses need to be conducted. Saitou andhis team are also leaders in these typesof analyses. ‘Indeed, I developed a novel
method, called ‘Neighbor-Joining method’,of extracting phylogenetic information during
my PhD that is still in use today,’ he enthuses.
‘Our research on new methods for molecular
evolutionary studies will mostly impact on
evolutionary biologists,’ he observes. However,
he comments that as the Neighbor-Joining
method (Saitou and Nei, 1987) is even now
widely used, not only for biologists, butalso for many people who are interested inphylogenetic trees, their future new methods
may also have a much broader impact. l

COLLABORATORS
Analyses of modern human genomes National Institute of Genetics (I Inoue),
Nagasaki University (K Yoshiura),
University of the Ryukyus (M Matsunami,S Maeda), Kanazawa University (A Tajima),
Genesis Health Care, Ltd., Tokyo
Analyses of ancient human genomes National Science Museum, Tsukuba(K Shinoda, H Kanzawa-Kiriyama),
Yamanashi University (N Adachi,T Tsunoda), Kanazawa University (T Sato,K Hosomichi)
Analyses of mammalian genomes Hokkaido University (H Suzuki, N Osada),
Ibaraki University (T Kitano), Southern
University of Science and Technology(I Barbarinde), National Institute ofGenetics (K Ikeo), University of Montreal(M Mahmoudisaber), Institute of Geneticsand Cytology (G Zhunussova,K Dossybayev)
TEAM MEMBERST A Jinam, R Suzuki, K Kryukov, K Dauyey
CONTACT DETAILS
Professor Naruya Saitou
T: +81 55 981 6790
E: saitounr@nig.ac.jp
W: http://www.yaponesian.jp/
W: http://www.saitou-naruya-laboratory.
org/english/
BIO
Professor Naruya Saitou graduated fromthe Department of Biology, the Universityof Tokyo in 1979. He gained his PhD fromthe University of Texas in 1986. In 1991
Saitou joined the National Institute ofGenetics as an Associate Professor, andwas promoted to a full Professor in 2002.