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I. CENTER FOR
INFORMATION BIOLOGY AND DNA DATA BANK OF JAPAN
I-a. Laboratory for DNA Data Analysis - Takashi
Gojobori Group
RESEARCH
ACTIVITIES
(16)
DDBJ in the stream of various biological
data
Satoru Miyazaki, Hideaki Sugawara, Kazuho Ikeo,
Takashi Gojobori and Yoshio Tateno
--In the past year
we at DDBJ (http://www.ddbj.nig.ac.jp)
have made a steady increase in the number of data
submissions with a 50.6% increment in the number of
bases or 46.5% increment in the number of entries.
Among them the genome data of man, ascidian and
rice hold the top three. Our activity has extended
to providing a tool that enables sequence retrieval
using regular expressions, and to launching our
SOAP server and web services to facilitate the
acquisition of proper data and tools from a huge
number of biological data resources on websites
worldwide. We have also opened our public gene
expression database, CIBEX.
(17)
Note on the maximum likelihood estimation of
haplotype frequencies
Shuhei Mano, Norikazu Yasuda, Toru Katoh,
Kenichi Tounai, Hidetoshi Inoko, Tadashi Imanishi,
Gen Tamiya and Takashi Gojobori
--The maximum
likelihood estimation (MLE) is one of the most
popular ways to estimate haplotype frequencies of a
population with genotype data whose linkage phases
are unknown. The MLE is commonly implemented in the
use of the Expectation-Maximization (EM) algorithm.
It is known that the EM algorithm carries the risk
that an estimator may converge erroneously to one
of the local maxima or saddle points of the
likelihood surface, resulting in serious errors in
the MLE of haplotype frequencies. In this note, by
theoretical treatments we present the necessary and
sufficient conditions that the local maxima or
saddle points on the likelihood surface appear. As
a rule of thumb, that the difference between the
coupling and repulsive haplotype frequencies in
phase known individuals is 3/2 times larger than
the frequency of phase ambiguous individuals is the
sufficient condition that the likelihood surface is
unimodal. Moreover, we present the analytic
solution to the biallelic two-locus problem, and
construct a general algorithm to obtain the global
maximum.
(18)
The evolutionary rate of a protein influenced by
features of the interacting partners
Takashi Makino and Takashi Gojobori
--We focused upon
how the evolutionary rates of proteins were
influenced by the characteristic features of PPIs.
Because the recent advancement of molecular
technologies enables us to understand actual
features of protein to protein interactions (PPIs),
it becomes possible to make objective descriptions
about the characteristic features of the proteins
in the PPI networks. In this analysis, we defined a
protein having a larger number of PPI partners of
the same functional class as the SF (Same Function)
protein, and a protein having a larger number of
PPI partners of different functional classes as the
DF (Different Function) protein. We also classified
proteins in the PPI networks into respective
proteins in dense and sparse parts of the PPI
network, denoting these proteins as the DP (Dense
part) and SP (Sparse Part) proteins, respectively.
Because these two classifications were independent
of each other, we classified the proteins in PPIs
further into the four categories, the SF-DP, SF-SP,
DF-DP and DF-SP proteins. Then, we compared the
evolutionary rates between the SF and DF proteins,
between the DP and SP proteins, and among the four
categories. As a result, we found that the DF
proteins evolved at a slower rate than the SF
proteins. We also found that the SP proteins
evolved at a slower rate than the DP proteins. In
particular, we pointed out that the DF-SP proteins
evolved at the slowest rate in the proteins
examined. Because all these differences in the
evolutionary rates are statistically significant,
it is suggested that the proteins with their PPI
partners belonging to different functional classes
and occupying a sparse part of the PPI network are
under strong functional constraints. It follows
that those proteins are very important for the
maintenance and survival of the PPI network.
(19)
Integrative annotation of 21,037 human genes
validated by full-length cDNA clones
Tadashi Imanishi, (154 authors), Takashi
Gojobori and Sumio Sugano
--The human genome
sequence defines our inherent biological potential;
the realization of the biology encoded therein
requires knowledge of the function of each gene.
Currently, our knowledge in this area is still
limited. Several lines of investigation have been
used to elucidate the structure and function of the
genes in the human genome. Even so, gene prediction
remains a difficult task, as the varieties of
transcripts of a gene may vary to a great extent.
We thus performed an exhaustive integrative
characterization of 41,118 full-length cDNAs that
capture the gene transcripts as complete functional
cassettes, providing an unequivocal report of
structural and functional diversity at the gene
level. Our international collaboration has
validated 21,037 human gene candidates by analysis
of high-quality full-length cDNA clones through
curation using unified criteria. This led to the
identification of 5,155 new gene candidates. It
also manifested the most reliable way to control
the quality of the cDNA clones. We have developed a
human gene database, called the H-Invitational
Database (H-InvDB; http://www.h-invitational.jp/).
It provides the following: integrative annotation
of human genes, description of gene structures,
details of novel alternative splicing isoforms,
non-protein-coding RNAs, functional domains,
subcellular localizations, metabolic pathways,
predictions of protein three-dimensional structure,
mapping of known single nucleotide polymorphisms
(SNPs), identification of polymorphic
microsatellite repeats within human genes, and
comparative results with mouse full-length cDNAs.
The H-InvDB analysis has shown that up to 4% of the
human genome sequence (National Center for
Biotechnology Information build 34 assembly) may
contain misassembled or missing regions. We found
that 6.5% of the human gene candidates (1,377 loci)
did not have a good protein-coding open reading
frame, of which 296 loci are strong candidates for
non-protein-coding RNA genes. In addition, among
72,027 uniquely mapped SNPs and
insertions/deletions localized within human genes,
13,215 nonsynonymous SNPs, 315 nonsense SNPs, and
452 indels occurred in coding regions. Together
with 25 polymorphic microsatellite repeats present
in coding regions, they may alter protein
structure, causing phenotypic effects or resulting
in disease. The H-InvDB platform represents a
substantial contribution to resources needed for
the exploration of human biology and pathology.
(20)
Japanese domesticated chickens derived from Shamo
traditional fighting cocks
Tomoyoshi Komiyama, Kazuho Ikeo, Yoshio Tateno
and Takashi Gojobori
--With the aim of
elucidating the evolutionary origin of Japanese
domesticated chickens, we examined 85 chicken mtDNA
sequences. Thirty-four various ornamental chickens,
42 fighting cocks (Shamo), and nine
long-crowing chickens (Naganakidori) were
included in these samples. Of the Shamo, 18
were sampled from Okinawa, while the remaining 24
were collected in other islands around Japan. In
addition, three Southeast Asian Junglefowls were
used as a reference to determine the common
ancestor of from Okinawa that clearly diverged from
the other Japanese domesticated chickens studied.
We found that all Japanese domesticated chickens,
including the ornamental varieties and
Naganakidori, were derived from the
ancestors of the Shamo in Okinawa. To create novel
varieties of ornamental chickens, intensive
artificial selection is imposed on ancestral
Shamo population, resulting in profoundly
differentiation of Japanese domesticated
chickens.
(21)
The evolutionary origin of long-crowing chicken:
its evolutionary relationship with fighting cocks
disclosed by the mtDNA sequence
analysis
Tomoyoshi Komiyama, Kazuho Ikeo, Yoshio Tateno
and Takashi Gojobori
--Chickens with
exceptionally long crow are often favored all over
the world, and connoisseur breeders have bred
certain types of chicken exclusively for this
trait. In Japan, three chicken varieties have been
specifically bred to develop an exceptionally long
crow of over 15 seconds. Although these three
long-crowing chickens, Naganakidori, are honored as
heritage varieties of Japan, the domestication
process and genealogical origin of long-crowing
chickens remain unclear. The purpose of this study
is to clarify these issues using nucleotide
sequences of the mitochondrial DNA D-loop region.
Blood samples from a total of nine long-crowing
chickens and 74 chickens from 11 Japanese native
varieties were collected. DNA sequence data of two
Junglefowl species were also collected from the
International DNA database (DDBJ /EMBL/GenBank) for
use as the outgroup. A phylogenetic tree was then
constructed revealing that all three Naganakidori
varieties were monophyletic and originated from a
fighting cock, a Shamo, for cockfighting. These
results suggest that these three long-crowing
chickens share a common origin in spite of their
conspicuously different characters, and that human
cultures favoring long-crowing chickens might have
been preceded by a tradition of cockfighting.
Moreover, these long-crowing varieties first
separated from the fighting cocks of Okinawa, which
is geographically closer to Southern China and
Indochina than Mainland Japan (Honshu/Kyushu). This
implies that Japanese long-crowing chickens were
first brought to Mainland Japan as fighting cocks
from the surrounding regions of Southern China or
Indochina and through Okinawa.
(22)
Novel algorithm for automated genotyping of
microsatellites
Toshiko Matsumoto, Wataru Yukawa, Yasuyuki
Nozaki, Ryo Nakashige, Minori Shinya, Satoshi
Makino, Masaru Yagura, Tomoki Ikuta, Tadashi
Imanishi, Hidetoshi Inoko, Gen Tamiya and Takashi
Gojobori
--Microsatellites
or short tandem repeats (STRs) are abundant in the
human genome with easily assayed polymorphisms,
providing powerful genetic tools for mapping both
Mendelian and complex traits. Microsatellite
genotyping requires detection of the products of
polymerase chain reaction (PCR) amplification by
electrophoresis, and analysis of the peak data for
discrimination of the true allele. A
high-throughput genotyping approach requires
computer-based automation at both the detection and
analysis phases. In order to achieve this,
complicated peak patterns from individual alleles
must be interpreted in order to assign alleles.
Previous methods consider limited types of noise
peaks and cannot provide enough accuracy. By
pattern recognition of various types of noise
peaks, such as stutter peaks and additional peaks,
we have achieved an overall average accuracy of 94%
for allele calling in our actual data. Our
algorithm is crucial for a high-throughput
genotyping system for microsatellite markers by
reducing manual editing and human errors.
(23)
Evolution of vitamin b6 (pyridoxine) metabolism by
gain and loss of genes
Tsuyoshi Tanaka, Yoshio Tateno and Takashi
Gojobori
--Vitamin B(6)
(VB6) functions as a cofactor of many diverse
enzymes in amino acid metabolism. Three metabolic
pathways for pyridoxal 5'-phosphate (PLP; the
active form of VB6) are known: the de novo
pathway, the salvage pathway, and the fungal type
pathway. Most unicellular organisms and plants
biosynthesize VB6 using one or two of these three
biosynthetic pathways. However, animals such as
insects and mammals do not possess any of the
pathways and, thus, need to intake VB6 in their
diet to survive. It is conceivable that breakdowns
of these pathways occurred in the evolutionary
lineages of insects and mammals, and one of the
major reasons for this would be the loss of
pertinent genes. We studied the evolution of VB6
biosynthesis from the view of the gain and loss of
10 pertinent genes in 122 species whose genome
sequences were completely determined. The results
revealed that each gene in the pathways was lost
more than once in the entire evolutionary lineages
of the 122 species. We also found the following
three points regarding the evolution of PLP
biosynthesis: (1) the breakdown of the PLP
biosynthetic pathways occurred independently at
least three times in animal lineages, (2) the de
novo pathway was formed by the generation of pdxB
in gamma-proteobacteria, and (3) the order of the
gene loss in VB6 metabolism was conserved among
different evolutionary lineages. These results
suggest that the evolution of VB6 metabolism was
subject to gains and frequent losses of related
genes in the 122 species examined. This dynamic
nature of the evolutionary changes must have been
responsible for the breakdowns of the pathways,
resulting in profound differentiation of
heterotrophy among the species.
(24)
Biased biological functions of horizontally
transferred genes in prokaryotic
genomes
Yoji Nakamura, Takeshi Itoh, Hideo Matsuda and
Takashi Gojobori
--Horizontal gene
transfer is one of the main mechanisms contributing
to microbial genome diversification. To clarify the
overall picture of interspecific gene flow among
prokaryotes, we developed a new method for
detecting horizontally transferred genes and their
possible donors by Bayesian inference with training
models for nucleotide composition. Our method gives
the average posterior probability (horizontal
transfer index) for each gene sequence, with a low
horizontal transfer index indicating recent
horizontal transfer. We found that 14% of open
reading frames in 116 prokaryotic complete genomes
were subjected to recent horizontal transfer. Based
on this data set, we quantitatively determined that
the biological functions of horizontally
transferred genes, except mobile element genes, are
biased to three categories: cell surface, DNA
binding and pathogenicity-related functions. Thus,
the transferability of genes seems to depend
heavily on their functions.
(25)
False positive selection identified by ML-based
methods: examples from the Sig1 gene of the
diatom Thalassiosira weissflogii and the
tax gene of a human T-cell lymphotropic
virus
Yoshiyuki Suzuki and Masatoshi Nei
--Sexually induced
gene 1 (Sig1) in the centric diatom
Thalassiosira weissflogii is considered to
encode a gamete recognition protein. Sorhannus
(2003) analyzed nucleotide sequences of Sig1
using parsimony analysis and the maximum-likelihood
(ML)-based Bayesian method for inferring positive
selection at single amino acid sites and reported
that positively selected sites were detected by the
latter method but not by the former. He then
concluded that for this type of study the ML-based
method is more reliable than parsimony analysis.
Here we show that his results apparently represent
false-positive cases of the ML-based method and
that there is no solid evidence that this gene
contains positively selected sites. We further
demonstrate that in the tax gene of human
T-cell lymphotropic virus type I (HTLV-I) all codon
sites, including invariable sites, can be inferred
as positively selected sites by the ML-based
method. These observations indicate that the
ML-based method may produce many false-positive
sites. One of the main reasons for the occurrence
of false positives is that in the ML-based method
codon sites are grouped into several categories
with different nonsynonymous/synonymous rate ratios
(ω's) on a purely statistical basis and positive
selection is inferred indirectly by examining
whether the average ω for each category is greater
than 1 or not. In parsimony analysis, however, the
evolutionary change of nucleotides at each codon
site is examined. For this reason, parsimony-based
methods rarely produce false positives and are
safer than ML-based methods for detecting positive
selection at individual codon sites, though a large
number of sequences are necessary.
(26)
Negative selection on neutralization epitopes of
poliovirus surface proteins: implications for
prediction of candidate epitopes for
immunization
Yoshiyuki Suzuki
--For development
of effective vaccines against viruses, it is of
importance to choose appropriate epitopes as the
target for immunization. These epitopes should
eventually be determined experimentally, but it
would be helpful if we could predict candidate
epitopes computationally because it accelerates the
entire process. To predict candidate epitopes for
immunization, it is of great interest to
characterize the target epitopes of poliovirus
vaccine, which has empirically proven to be the
most effective among all vaccines available. Here I
show that almost all amino acid sites of poliovirus
surface proteins VP1, VP2, and VP3 including
neutralization epitopes are negatively selected and
no site is under positive selection. These results,
together with those obtained in previous studies,
indicate that vaccines directed against epitopes
which consist of negatively selected sites protect
vaccinees more effectively than those directed
against epitopes which contain positively selected
sites. These observations suggest that candidate
epitopes for immunization are predicted by the
molecular evolutionary analysis of viral protein
(and its coding nucleotide) sequences, as the
epitopes which consist exclusively of negatively
selected amino acid sites.
(27)
New Methods for Detecting Positive Selection at
Single Amino Acid Sites
Yoshiyuki Suzuki
--Inferring
positive selection at single amino acid sites is of
particular importance for studying evolutionary
mechanisms of a protein. For this purpose, Suzuki
and Gojobori (1999) developed a method (SG method)
for comparing the rates of synonymous and
nonsynonymous substitutions at each codon site in a
protein-coding nucleotide sequence, using ancestral
codons at interior nodes of the phylogenetic tree
as inferred by the maximum parsimony method. In the
SG method, however, selective neutrality of
nucleotide substitutions cannot be tested at codon
sites, where only termination codons are inferred
at any interior node or the number of equally
parsimonious inferences of ancestral codons at all
interior nodes exceeds 10,000. Here I present a
modified SG method which is free from these
problems. Specifically, I use the distance-based
Bayesian method for inferring the single most
likely ancestral codon from 61 sense codons at each
interior node. In the computer simulation and real
data analysis, the modified SG method showed a
higher overall efficiency of detecting positive
selection than the original SG method particularly
at highly polymorphic codon sites. These results
indicate that the modified SG method is useful for
inferring positive selection at codon sites where
neutrality cannot be tested by the original SG
method. I also discuss that the p-distance is
preferable to the number of synonymous
substitutions for inferring the phylogenetic tree
in the SG method, and present a maximum likelihood
method for detecting positive selection at single
amino acid sites, which produced reasonable results
in the real data analysis.
(28)
Three-dimensional window analysis for detecting
positive selection at structural regions of
proteins
Yoshiyuki Suzuki
--Detection of
natural selection operating at the amino acid
sequence level is important in the study of
molecular evolution. Single site analysis and
one-dimensional window analysis can be used to
detect selection when the biological functions of
amino acid sites are unknown. Single site analysis
is useful when selection operates more or less
constantly over evolutionary time, but less so when
it operates temporarily. One-dimensional window
analysis is more sensitive than single site
analysis when the functions of amino acid sites in
close proximity in the linear sequence are similar
although this is not always the case. Here I
present a three-dimensional window analysis method
for detecting selection given the three-dimensional
structure of the protein of interest. In the
three-dimensional structure, the window is defined
as the sphere centered on the α-carbon of an amino
acid site. The window size is the radius of the
sphere. The sites whose α-carbons are included in
the window are grouped for the neutrality test. The
window is moved within the three-dimensional
structure by sequentially moving the central site
along the primary amino acid sequence. To detect
positive selection, it may also be useful to group
the surface-exposed sites in the window separately.
Three-dimensional window analysis appears to be not
only more sensitive than single site analysis and
one-dimensional window analysis, but also provides
similar specificity for inferring positive
selection in the analyses of the hemagglutinin and
neuraminidase genes of human influenza A viruses.
This method, however, may fail to detect selection
when it operates only on a particular site, in
which case single site analysis may be preferred
although a large number of sequences is
required.
(29)
Evolutionary process of amino Acid biosynthesis in
corynebacterium at the whole genome
level
Yousuke Nishio, Yoji Nakamura, Yoshihiro Usuda,
Shinichi Sugimoto, Kazuhiko Matsui, Yutaka
Kawarabayasi, Hisashi Kikuchi, Takashi Gojobori and
Kazuho Ikeo
--Corynebacterium
glutamicum, which is the closest relative of
Corynebacterium efficiens, is widely used
for the large scale production of many kinds of
amino acids, particularly glutamic acid and lysine,
by fermentation. Corynebacterium
diphtheriae, which is well known as a human
pathogen, is also closely related to these two
species of Corynebacteria, but it lacks such
productivity of amino acids. It is an important and
interesting question to ask how those closely
related bacterial species have undergone such
significant functional differentiation in amino
acid biosynthesis. The main purpose of the present
study is to clarify the evolutionary process of
functional differentiation among the three species
of Corynebacteria by conducting a comparative
analysis of genome sequences. When Mycobacterium
and Streptomyces were used as out groups, our
comparative study suggested that the common
ancestor of Corynebacteria already possessed almost
all of the gene sets necessary for amino acid
production. However, C. diphtheriae was
found to have lost the genes responsible for amino
acid production. Moreover, we found that the common
ancestor of C. efficiens and C.
glutamicum have acquired some of genes
responsible for amino acid production by horizontal
gene transfer. Thus, we conclude that the
evolutionary events of gene loss and horizontal
gene transfer must have been responsible for
functional differentiation in amino acid
biosynthesis of the three species of
Corynebacteria.
PUBLICATIONS
Papers
1. Nakamura, Y., Itoh, T., Matsuda, H. and
Gojobori, T. (2004). Biased biological functions of
horizontally transferred genes on 324,653 open
reading frames of 116 prokaryotic complete genomes.
Nature Genetics 36, 760-6.
2. Iwama, H. and Gojobori, T. (2004). Highly
conserved upstream sequences for transcription
factor genes and implications for the regulatory
network. Proc. Natl. Acad. Sci. USA
101, 17156-61.
3. Imanishi, T. and other 152 authors,
*Gojobori, T. and Sugano S. (2004).
Integrative annotation of 21,037 human genes
validated by full-length cDNA clones. PLoS
Biology 2, 1-21.
*Correspondence Author
4. Ogura, A., Ikeo, K. and Gojobori, T. (2004).
Comparative analysis of gene expression for
convergent evolution of camera eye between octopus
and human. Genome Res. 14,
1555-61.
5. Andrews, T.D. and Gojobori, T. (2004). Strong
positive selection and recombination drive the
antigenic variation of the PilE protein of the
human pathogen neisseria meningitidis.
Genetics 166, 25-32.
6. Hanada, K., Suzuki, Y. and Gojobori, T. (2004).
A large variation in the rates of synonymous
substitution for RNA viruses and its relationship
to a diversity of viral infection and transmission
modes. Mol Biol Evol. 21,
1074-80.
7. Jung Shan, H., Kobayashi, C., Agata, K., Ikeo,
K. and Gojobori, T. (2004). Detection of apoptosis
during planarian regeneration by the expression of
apoptosis-related genes and TUNEL assay.
GENE 333, 15-25.
8. Komiyama, T., Ikeo, K. and Gojobori, T. (2004).
The evolutionary origin of long-crowing chicken:
its evolutionary relationship with fighting cocks
disclosed by the mtDNA sequence analysis.
GENE 333, 91-99.
9. Komiyama, T., Ikeo, K., Tateno, Y. and
Gojobori, T. (2004). Japanese domesticated chickens
have been drived from Shamo, traditional fighting
cocks. Mol. Phylogenet. Evo.
33, 16-21.
10. Mano, S., Yasuda, N., Katoh, T., Tounai, K.,
Inoko, H., Imanishi, T., Tamiya, G. and Gojobori,
T. (2004). Notes on the maximum likelihood
estimation of haplotype frequescies. Ann Hum
Genet. 68, 257-64.
11. Matsumoto, T., Yukawa, W., Nozaki, Y.,
Nakashige, R., Shinya, M., Makino, S., Yagura, M.,
Ikuta, T., Imanishi, T., Inoko, H., Tamiya, G. and
Gojobori, T. (2004). Novel algorithm for
automated genotyping of microsatelites.
Nucleic Acids Res. 32,
6069-77.
12. Tanaka, T., Tateno, Y. and Gojobori, T. (2004).
Evolution of vitamin B6 (Pyridoxine) metabolism by
gain and loss of genes. Mol. Biol.
Evol.
13. Alexopoulos, H., Bottger, A., Fischer, S.,
Levin, A., Wolf, A., Fujisawa, T., Hayakawa, S.,
Gojobori, T., Davies, J., David, C. and Bacon, J.
(2004). Evolution of gap junctions: the missing
link? Curr. Biol. 14 (20),
R879-80.
14. Bellgard, M., Ye, J., Gojobori, T. and Appels,
R. (2004). The bioinformatics challenges is
comparative analysis of cereal genomes-an overview.
Funct. Integr. Genomics 4,
1-11.
15. Kadota, M., Nishigaki, R., Wang, C.C., Toda,
T., Shirayoshi, Y., Inoue, T., Gojobori, T.,
Ikeo, K., Rogers, M.S. and Oshimura, M. (2004).
Containing a single human chromosome 21 in neuronal
differentiation: an in vitro model of Down
syndrome. Neuroscience 129
(2), 325-35.
16. Miyazaki, S., Sugawara, H., Ikeo, K., Gojobori,
T. and Tateno, Y. (2004). DDBJ in the stream of
various biological data. Nucleic Acids
Res 32, D31-4.
17. Nishio, Y., Nakamura, Y., Usuda, Y., Sugimoto,
S., Matsui, K., Kawarabayashi, Y., Kikuchi, H.,
Gojobori, T. and Ikeo, K. (2004).
Evolutionary process of the amino acids
biosynthesis in Corynebacterium at the whole genome
level. Mol. Biol. Evol. 21,
1683-91.
18. Suzuki, Y. (2004). Negative selection on
neutralization epitopes of poliovirus surface
proteins: implications for prediction of candidate
epitopes for immunization. Gene
328, 127-133.
19. Suzuki, Y. (2004). New methods for
detecting positive selection at single amino acid
sites. J. of Mol. Evol. 59,
11-19.
20. Suzuki, Y. and Nei, M. (2004). False
positive selection identified by ML-based methods:
examples from the Sig1 gene of diatom Thalassiosira
weissflogii and the tax gene of a human T-cell
lymphotropic virus. Molecular Biology and
Evolution 21, 914-921.
21. Suzuki, Y. (2004). Three-dimensional window
analysis for detecting positive selection at
structural regions of proteins. Mol Biol and
Evol 21, 2352-2359.
22. Toyoda, R., Kasai, A., Sato, S., Wada, S.,
Saiga, H., Ikeo, K., Gojobori, T.,
Numakunai, T. and Yamamoto, H. (2004). Pigment cell
lineage-specific expression activity of the
ascidian tyrosinase-related gene.
GENE 332, 61-69.
23. Wang, C.C., Kadota, M., Nishigaki, R., Kazuki,
Y., Shirayoshi, Y., Rogers, M.S., Gojobori,
T., Ikeo, K. and Oshimura, M. (2004).
Molecular hierarchy in neurons differentiated from
mouse ES cells containing a single human chromosome
21. Biochem. Biophys. Res. Commun.
314, 335-50.
24. 伊藤
剛,五條堀孝（2004）「ゲノミクス・プロテオミクスの新展開」第5節比較ゲノム（進化）微生物のゲノム進化解析,エヌ・ティ・エス,897-903.
25.
小笠原倫大,五條堀孝（2004）「病理診断における分子生物学―第一部16.バイオインフォマティクス」『病理と臨床』臨時増刊号,91-97.
26.
五條堀孝（2004）「総合化生命科学としての現代進化学」（巻頭言）『科学』10月号,1203.
27.
五條堀孝（2004）「バイオインフォマティクス―生命の多様性と進化に基づく生命科学の統合化にむけて」『総研大ジャーナル』5号,26-28.
28. 田中 剛,五條堀孝（2004）「特集
分子進化学の現在・ゲノムの比較解析と分子進化」『生体の科学』55巻,241-6.
29.
花田耕介,五條堀孝（2004）「ゲノムの再編成」第一章ヒトゲノムの全貌『Molecular
Medicine』増刊号,中山書店,101-109.
30.
溝上雅史,花田耕介,五條堀孝（2004）「ウイルス性肝炎（上）」日本臨床62巻,76-80.
Reviews
31. 五條堀孝・Hwang Jung
Shan・田中信彦,「ヒトにおけるヒドラ遺伝子」,生体の科学第55巻5号,2004年10月
ORAL
PRESENTATIONS
1. T. Gojobori "Genomics Data Banks and
Biotechnology/Bioinformatics" The 28th IUBS General
Assembly & The IUBS Conference International
Conference Biological Sciences, Development and
Society, Cairo Sheraton Hotel, Cairo, Egypt,
January, 2004.
2. T. Gojobori "New Developments in Evolutionary
Genomics" Gordon Research Conference on Structural,
Functional & Evolutionary Genomics, Four Points
Sheraton: Harbortown Ventura, California, USA,
February, 2004.
3. T. Gojobori "Evolution of central nervous system
from the viewpoint of gene expression" Molecular
Bases of Organismal Diversity and Evolution,
Kyoto-Tersa, Kyoto, Japan, February, 2004.
4. T. Gojobori "Activities of Human Full-length
cDNA Annotation Project and H-Invitational
Database", First ISN Special Neurochemistry
Conference, Avignon, France, May, 2004.
5. T. Gojobori "A new horizon of evolutionary
genomics: An effective usage of bioinformatics
toward integrative biology", Consiglio Scientifico
2004, Grand Hotel Vesuvio, Napoili, Italy, May,
2004.
6. T. Gojobori "Origins and evolution of the
central nervous system in animals: gene expression
profiles in hydra neural cells and planarian
brain.", Genome & Evolution 2004: SMBE Meeting,
Pennsylvania State University, Pennsylvania, USA,
June, 2004.
7. T. Gojobori "Greetings and overview of
H-Invitational Disease Edition Project",
H-Invitational Disease Edition Preparatory Meeting
4, National Institute of Advanced Industrial
Science and Technology: AIST, Tokyo Japan, June,
2004.
8. Yoshiyuki Suzuki "New methods for detecting
positive selection at single amino acid sites"
Genomes and Evolution, State College, USA, June,
2004.
9. T. Gojobori "Evolutionary implication of
horizontally transferred genes that were revealed
by the sequence comparisons of more than 110
prokaryotic complete genomes.", Structural
approaches to sequence evolution: Molecules,
networks, populations, Dresden, Germany, July,
2004.
10. Yoshiyuki Suzuki "Origin and evolution of
influenza virus hemagglutinin genes" National
Institute of Genetics Colloquium, Mishima, Japan,
July, 2004.
11. T. Gojobori "Search for the evolutionary origin
of the CNS: Comparative studies of gene expression
in planarian and hydra neural cells", Origins and
Evolution of The Nervous Systems, Cold Spring
Harbor Laboratory, Cold Spring Harbor, New York,
USA, August, 2004.
12. T. Gojobori "Greetings, self introduction &
overview" H-Invitational DE Jamboree National
Institute of Advanced Industrial Science and
Technology: AIST, Tokyo, Japan, September,
2004.
13. Lihua Jin, Yoshiyuki Suzuki, Kazuho Ikeo and
Takashi Gojobori: Evolutionary study of
small-RNA-mediated gene silencing pathways by
investigating the evolution of Rnase III
enzymes日本遺伝学会第76回大会,Suita, Osaka, Japan,
September, 2004.
14. T. Gojobori "Genome Evolution", International
Lecture in Bioinformatics and Genomics in
Collaboration with the Chinese Academy of Sciences
and SOKENDAI, Shanghai, China, October, 2004.
15. T. Gojobori "New Developments of Human
Full-length cDNA Annotation Invitational
(H-Invitational) Data Base", The 2nd International
Conference on Bioinformatics and Computational
Biology, Hotel do Frade Beach and Golf Resort,
Angra dos Reis, Brazil, October, 2004.
16. 五條堀 孝
バイオインフォマティシャン養成講座、キメック株式会社、神戸ポートアイランド、神戸市、2004年2月
17. 五條堀
孝「予防健康を目指したゲノム情報研究の今」長浜バイオ大学開学1周年記念講演会、長浜バイオ大学、長浜市、2004年3月
18. 五條堀
孝「ゲノム・インフォマティクス」第12回国際医療協力シンポジウム・多因子疾患の解明と克服:多因子疾患における研究、国際医療センター、東京都新宿区、2004年3月
19. 五條堀
孝「臨床分野におけるバイオインフォマティクスの活用と今後の課題」JBIC臨床インフォマティクス分野の開拓に関するシンポジウム、虎ノ門パストラル、東京都港区、2004年3月
20. 五條堀
孝「水産資源生物のゲノム活用とバイオインフォマティクスの役割」中央水産研究所、横浜市、2004年3月
21. 五條堀
孝「バイオインフォマティクス研究におけるDDBJの役割」DDBJing講習会、国立情報学研究所学術総合センター、東京都千代田区、2004年3月
22. 五條堀
孝「遺伝子発現解析分野の開発課題における今後の課題」第2回遺伝子発現解析分野における技術交流会、虎ノ門パストラル、東京都港区、2004年4月
23. 五條堀 孝
福岡大学平成16年度集中講義“地球圏科学特別会議V"福岡大学理学部、福岡市、2004年4月
24. 五條堀
孝「脳・神経系の進化的起源を求めて―ゲノムと遺伝子発現の比較解析―」進化多様性生物学大講座・公開シンポジウムオープンラボラトリー、東京大学理学部、東京都文京区、2004年6月
25. 五條堀
孝「バイオデータベースの現状と課題―バイオインフォマティクスの将来展望」第5回JBICバイオDBセミナー、虎ノ門パストラル、東京都港区、2004年7月
26. 五條堀
孝「本プロジェクトへのDDBJの関わり方、DDBJの役割」FANTOM
3 Steering
Meeting、ホテルルナミラー、横浜市、2004年7月
27. 五條堀
孝「ゲノム解析及び遺伝子発現プロファイル研究とその健康予防産業への応用可能性について」首都圏バイオゲノムベンチャーネットワーク平成16年度総会及び研究会、東葛テクノプラザ、千葉県柏市、2004年7月22日
28. 五條堀
孝「DNA配列とゲノムレベルの情報にもとづく分子進化の研究」日本進化学会第6回大会木村資生博士記念学術賞受賞講演、東京大学教養学部講堂、東京都目黒区、2004年8月
29. 五條堀
孝「ヒドラやプラナリアにみる遺伝子発現パターンと脳・神経系の進化的起源」日本進化学会第6回大会シンポジウム6D1ゲノムと遺伝子発現からみた生物進化の様相、東京大学教養学部、東京都目黒区、2004年8月
30. 五條堀
孝「ヒトゲノムアノテーションから病因遺伝子へ」Bio
Japan 2004
セッション名:生命システムの解明ヘ“バイオインフォマティクスの次の展開"、新高輪プリンスホテル、東京都品川区、2004年9月
31. 五條堀
孝「ゲノムや遺伝子発現パターンの異種間比較に基づく生物進化機構の研究について」第63回日本癌学会学術総会
特別企画セッション名:SP3生物多様性とがん研究への期待―進化とゲノム―、福岡国際会議場、福岡市、2004年10月
32. 五條堀 孝「国立遺伝学研究所
生命情報・DDBJ研究センターの活動とその成果の活用〜ゲノム情報を用いた健康情報産業に関する今後の展開とモバイル型の測定機器の開発ニーズ〜」バイオ・ゲノムベンチャー技術交流会・国立遺伝学研究所と開発型企業との交流会〜、虎ノ門パストラル、東京都港区、2004年11月
33.
塩生真史、由良敬、萩野圭、土方敦司、平島義紀、中原拓、江口達也、篠田和紀、山口晶大、高橋健一、伊藤剛、今西規、五條堀孝、郷通子「選択的スプライシングによるタンパク質立体構造への影響」日本生物物理学会第42回年会、国立京都国際会館、京都市、2004年12月
34. 鈴木 善幸「New methods for detecting positive
selection at single amino acid
sites」第6回日本進化学会総会、世田谷区駒場、2004年8月
35.
牧野能士、五條堀孝「タンパク質間相互作用ネットワークの進化的解析」日本遺伝学会第76回大会、大阪府吹田市、2004年9月
POSTER
PRESENTATIONS
1. Yoshiyuki Suzuki "Positive and negative
selection on viral proteins" Gordon Research
Conference on Structural, Functional &
Evolutionary Genomics, Ventura, USA, February,
2004.
2. Kengo Yoshida, Jung Shan Hwang, Toshitaka
Fujisawa, Chiemi Fujisawa, Takashi Gojobori
"Seeking for signs of aging in hydra, a primitive
metazoan" Cold Spring Harbor Meeting, Molecular
Genetics of Aging, Cold Spring Harbor, New York,
October, 2004.
3. Qing-Xin Liu, Kazuho Ikeo, Susumu Hirose and
Takashi Gojobori. Coevolution of MBF1 and TBP
across the species from Archaea to human.
27th Annual Meeting of Molecular Biology Society of
Japan, Kobe, Japan, December, 2004.
4. Roberto Barrero, Takuro Tamura, Hitomi Sakurai,
Shiho Hayakawa, Yoshio Tateno, Kazuho Ikeo, Tadashi
Imanishi, Takashi Gojobori. microRNAs: biology and
evolution.第27回日本分子生物学会年会,Kobe, Japan
December, 2004.
5. 吉田健吾、Jung Shan
Hwang、藤澤敏孝、藤澤千笑、池尾一穂、五條堀孝「ヒドラは老化するか―多細胞動物における老化の起源―」日本分子生物学会第27回年会、神戸、2004年12月
6.
大里直樹、池尾一穂、五條堀孝「アンチセンスmRNA候補遺伝子の生物種間の比較解析」第27回日本分子生物学会年会、神戸市、2004年12月
7.
田中信彦、横山竦三、池尾一穂、五條堀孝「cDNAマイクロアレイを用いたメキシカンテトラの地上型から洞窟型への進化に関わる遺伝子の探索」、日本分子生物学会第27回大会、神戸市、2004年12月
8. 早川志帆、Barrero,
Roberto、櫻井仁美、田村卓郎、舘野義男、池尾一穂、今西規、五條堀孝:「新規哺乳類マイクロRNAの予測」、第27回日本分子生物学会年会、神戸、2004年12月
9. 櫻井仁美、Roberto
Barrero、早川志帆、田村卓郎、舘野義男、池尾一穂、今西規、五條堀孝:「哺乳類マイクロRNAの標的遺伝子予測と実験的検証」第27回日本分子生物学会年会・神戸、2004年12月
EDUCATION
1. Y. Suzuki “Methods for detecting positive
selection at single amino acid sites" The Graduate
University of Advanced Studies, Hayama, April,
2004.
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