Vol.2, No.6, 458-464 (2009)
doi:10.4236/jbise.2009.26066
SciRes Copyright © 2009 Openly accessible at http://www.scirp.org/journal/JBISE/
JBiSE
Trends in global warming and evolution of polymerase
basic protein 2 family from influenza a virus
Shao-Min Yan1, Guang Wu2
1National Engineering Research Center for Non-food Biorefinery, Guangxi Academy of Sciences, Nanning, China; 2Computation al
Mutation Project, DreamSciTech Consulting, Shenzhen, China.
Email: hongguanglishibahao@yahoo.com
Received 9 June 2009; revised 25 June 2009; 29 June 2009.
ABSTRACT
Both global warming and influenza trouble hu-
mans in varying ways, therefore it is important
to study the trends in both global warming and
evolution of influenza A virus, in particular,
proteins from influenza A virus. Recently, we
have conducted two studies along this line to
determine the trends between global warming
and polymerase acidic protein as well as matrix
protein 2. Although these two studies reveal
some interesting findings, many studies are still
in need because at least there are ten different
proteins in influenza A virus. In this study, we
analyze the trends in global warming and evo-
lution of polymerase basic protein 2 (PB2) from
influenza A virus. The PB2 evolution from 1956
to 2008 was defined using the unpredictable
portion of amino-acid p air. Then the trend in this
evolution was compared with the trend in the
global temperature, the temperature in north
and south hemispheres, and the temperature in
influenza A virus sampling site and species
carrying influenza A virus. The results show the
similar trends in global warming and in PB2
evolution , which are in good agreem ent with our
previous studies in polymerase acidic protein
and matrix protein 2 from influenza A v irus.
Keywords: Global Warming; Influenza; Virus; Po-
lymerase Bas ic Protein 2
1. INTRODUCTION
Changes in environmental conditions can rapidly shift
allele frequencies in populations of species with rela-
tively short generation times [1]. The global warming
imposes the new danger not only on environments, but
also on humans and various species [2]. As a result we
would see the composition of species, such as proteins,
under the influence of global warming although some
proteins could be hidden deeply inside cells. Thus, it is
important to compare the trends in global warming and
protein evolution of interest family in order to see if
there are similar trends in both.
Accordingly, we recently conducted two studies to
analyze the trend in both global warming and evolution
of polymerase acidic protein (PA) [3] and matrix protein
2 [4] from influenza A virus.
It is well known that the evolution of protein family is
a process of mutations, and th erefore we could represent
this evolution if we could represent mutated proteins
along the time course. We need to do so because the
global warming is the change in temperature over time.
However, a mutation in protein is an event of changing
one letter to another because amino acids in protein are
presented as 20 letters, which are neither scalar data nor
victors, whereas the temperature is a scalar datum.
This means that we need to convert the letter-based
proteins into scalar data in order to plot them along the
time course to see their evolutionary trend. Since 1999,
our group has developed three approaches to convert
either a single amino acid or a protein into a scalar da-
tum based on random principle (for review, see [5,6,7,8]).
Using our approaches, we can effectively represent a
protein family over time, which provides the basis for
conducting the study on analyzing the trends in global
warming and evolution of proteins of interest.
At this moment, we are particularly interest in the po-
lymerase basic protein 2 (PB2) form influenza A virus,
because it is a subunit of RNA-dependent RNA poly-
merase complex associated with the transcription and
replication of the influenza A viral genome [9]. The PB2
subunit interacts with PA in th e cytoplasm initially an d is
subsequently transported as a dimer into the n uc leus [10 ].
The viral RNA polymerase complex is important for the
efficient propagation of the virus in the host and for its
adaptation to new hosts [11], and considered as a major
determinant of the pathogenicity of the 1918 pandemic
viru s [12].
S. M. Yan et al. / J. Biomedical Science and Engineerin g 2 (2009) 458-464
SciRes Copyright © 2009 http://www.scirp.org/journal/JBISE/
459
Global temperature anomaly
-.4
-.2
0.0
.2
.4
.6
Year
1956 1961 1966 1972 1977 1982 1987 1992 1998 2003 2008
63
64
65
66
67
68
Unpredictable portion (%)
Figure 1. Global temperature anomaly (°C) and evolution of PB2 proteins from influenza A viruses. The dotted lines and points
were regressed lines and the mean of all PB2 proteins at a given year (n = 2397 from 1956 to 2008).
The mutations in PB2 protein can affect the virulence
of influenza A virus [13], change RNA binding activity
[14,15], and contribute to intra- and inter-host transmis-
sion in diverse virus backgrounds [15,16].
Openly accessible at
The aim of this study is to use the unpredictable por-
tion of amino-acid pair to convert symbolised PB2 pro-
teins into numerical data, and then to analyze the trends
in global warming and the evolution of PB2 proteins
from influenza A virus, in order to explore the potential
impact of glob a l warming on prot ei n ev olution.
2. MATERIALS AND METHODS
2.1. Temperature Data
The global, north and south hemispheric temperature
anomalies from 1850 to 2007, whose anomaly is based
on the period 1961-1990, were obtained from Had-
CRUT3v [17,18]. The local temperature from 1956 to
1998 based on 0.5 by 0.5° latitude and longitude grid-
box basis cross globe was obtained from New et al. [19].
2.2. PB2 Data
A total of 509 2 full-length PB2 sequences of influenza A
virus sampled from 1956-2008 was obtained from the
influenza virus resources [20]. After excluded identical
sequences, 2397 PB2 proteins were used in this study.
2.3. Converting PB2 Proteins into Scalar
Data
For presenting PB2 protein family along the time course,
we need to convert each PB2 protein into a scalar datum,
which must differ for different PB2 proteins. Among our
three random approaches (for review, see [5,6,7,8]), the
simplest one is the amino-acid pair predictability, by
which we view if the combination of two adjacent amino
acids can be explained by the permutation. For a whole
protein, we can determine the percentage of how many
amino-acid pairs can be predicted according to the per-
mutation. We have used this method in many studies (for
publications in 2008, see [21,22,23,24,25]).
For a PB2 protein, we counted the first and second
amino acids as a pair, the second and third amino acids
as another pair, until the next to terminal and the termi-
nal amino acids as the last pair. Then, we determined
whether an amino-acid pair could be explained by per-
mutation, or predicted by random mechanism in other
S. M. Yan et al. / J. Biomedical Science and Engineerin g 2 (2009) 458-464
SciRes Copyright © 2009 Openly accessible at http://www.scirp.org/journal/JBISE/
460
Anomaly temperature
-.4
-.2
0.0
.2
.4
.6
63
64
65
66
67
68
Unpredic tabl e portion (%)
Anomaly temperature
-.4
-.2
0.0
.2
.4
Year
1956 1961 1966 1972 1977 1982 1987 1992 1998 2003 2008
62
63
64
65
66
67
68
69
70
Unpredictable portion (%)
North hemisphere
South hemisphere
Figure 2. Trends in temperature and PB2 evolution grouped according to north (n = 2177) and south (n = 220) hemispheres. The
dotted lines were regressed lines.
S. M. Yan et al. / J. Biomedical Science and Engineerin g 2 (2009) 458-464
SciRes Copyright © 2009 Openly accessible at http://www.scirp.org/journal/JBISE/
461
words. Finally, we calculated the percentage of how
many amino-acid pairs were predictable and unpredict-
able in a PB2 protein.
For example, a PB2 protein (strain A/Virginia/UR06-
0139/2007(H1N1) and accession number ABW40267)
was composed of 759 amino acids. There were 53
threonines “T” and 59 arginines “R” in this protein. If
the appearance of amino-acid pair TR could be ex-
plained by the permutation, it would appear 4 times in
the PB2 protein (53/75959/758758=4.12). Act   ually
there were 4 pairs of TR in it, so the appearance of TR
was predictable. By clear contrast, there were 34 aspara-
gines “N” and 28 prolines “P” in this PB2 protein. Ac-
cording to the permutation, the amino-acid pair NP
would appear once (34/75928/758=1.25) in this pr o-
tein. However, it appeared 5 times in realty, which was
unpredictable. In this way, we classified all of the
amino- acid pairs in ABW40267 PB2 protein as predict-
able and unpredictable.
It is absolutely necessary that the predictable/unpre-
dictable portion is subject to a tiny difference between
two PB2 proteins, thus different PB2 proteins should
have different values to be distinguishable. In the past,
we have tested many proteins to verify this request and
got the positive answer [3,4,5,6,7,8,21,22,23,24,25]. For
instance, the predictable and unpredictable portions were
36.49% and 63.51% for AB W40267 PB 2 prot ein. Ano t he r
human H1N1 influenza A virus was isolated from USA
in 2007, its PB2 protein (accession number ABW 40410)
had only one amino acid at position 108 different from
that of ABW40267 PB2 protein. However, its predictable
and unpredictable portions were 36.82% and 63.18%.
In this manner, we converted 2397 letter-symbolized
PB2 proteins into 2397 scalar data [26]. As each PB2
protein had its sampling year, we thus had two scalar
datasets, the temperature recorded each year and the
unpredictable portion of PB2 protein sampled each year.
Hence we could plot both datasets along the time course
to observe their trends.
3. RESULTS AND DIS CUS SION
Figure 1 showed the trends in both global warming and
evolution of PB2 proteins, where both trends revealed
similar as indicated by their regressed lines. The unpre-
dictable portion of PB2 proteins increased over time,
which was similar to that the global temperature in
creased along the time course.
Year
1956 1960 1964 1969 1973 1977 1981 1985 1990 1994 1998
61
63
65
67
69
71
73
Unpredictable portion (%)
Temperature per se
-15
-5
5
15
25
35
Figure 3. Point-to-point temperature versus PB2 proteins (n=828) from 1956 to 1998. Each point presented a local temperature (°C)
at the given year (upper panel), corresponding to the place where a PB2 protein was sampled (lower panel). The dotted lines were
regressed lines.
S. M. Yan et al. / J. Biomedical Science and Engineerin g 2 (2009) 458-464
SciRes Copyright © 2009 Openly accessible at http://www.scirp.org/journal/JBISE/
462
Tem pe rature
-20
-10
0
10
20
30
40
Unpredictable portion
60
62
64
66
68
70
72
74
Temperature
-10
0
10
20
30
40
A vian (n = 394)
Unpredictable portion
60
62
64
66
68
70
Human (n = 289)
Temperature
-5
0
5
10
15
20
25
30
Y
ear
1956 1960 1964 1969 1973 1977 1981 1985 1990 1994 1998
Unpredictable portion
62
64
66
68
70
72
Swine (n = 78)
Figure 4. Point-to-point temperature (°C) versus PB2 proteins sampled from different species. The dotted lines were regressed lines.
S. M. Yan et al. / J. Biomedical Science and Engineerin g 2 (2009) 458-464
SciRes Copyright © 2009 http://www.scirp.org/journal/JBISE/
463
Openly accessible at
On the other hand, we cannot ignore these trends be-
cause we cannot create another earth without global
warming but with active influenza virus for comparison
over the same time span. As the validation of global
warming is done through the comparison along the time
course, we would argue that the validation of PB2 evo-
lution should also be done along the time course, i.e. the
comparison between any two different time points.
Moreover, the global temperature was generally di-
vided into north and south hemisphere, so we could
group PB2 proteins accordingly to see if the trend still
held on in such circumstance. As shown in Figure 2, the
similar trend was clearer in north hemisphere than in
south one, which could be explained by the fact that
most of PB2 proteins were sampled in north hemisphere. This study demonstrated the changes in the unpre-
dictable portions of PB2 proteins were different in dif-
ferent species. In human and swine, the trends of evolu-
tion of PB2 proteins were similar to that of temperature,
but not in avian (Figure 4). This difference can be due to
the fact that the place where avian was sampled would
not be the place where the mutation occurred, because
migratory birds are common reservoirs responsible for
spreading avian influenza viruses [28,29,30,31]. Climate
change would almost certainly alter bird migration, in-
fluence the avian influenza virus transmission cycle and
directly affect virus survival outside the host [32,33]. On
the other hand, the human and swine were generally lo-
calized, thus the present results indicate the potential
impact of global warming on the evolution of influenza
A viruses.
Actually the data of PB2 proteins in Figures 1 and 2
were averaged in each year. For example, there were
only 2 samples in 1956, but 220 PB2 pro teins were sam-
pled in 2007. Another way to analyze the trends is to
apply the point-to-point method, that is, we coupled each
PB2 protein with the temperature according to its sam-
pling place and year. In other word, we took the tem-
perature measured at each geographical latitude and lon-
gitude of the place where a PB2 protein was sampled at
the same year to make the comparison.
Figure 3 displayed 828 point-to-point relationships
between temperature and unpredictable portion of PB2
proteins from 1956 to 1998, and their regression indi-
cated the similar trends. The results in Figure 3 were in
consistent with what we found in Figures 1 and 2, that is,
there were similar trends between global warming and
evolution of PB2 prote ins. Global climate changes affect the functioning of eco-
systems, in particular host-pathogen interactions, with
major consequences in health ecology [34,35,36]. The
results in this study are in good ag reement with our pre-
vious studies [3,4], thus these results furthermore sug-
gest the general trend in evolution of proteins from in-
fluenza A virus. However, much studies are in need be-
cause there are still seven other proteins from influenza
A virus, which we have yet to study.
Because influenza viruses were hosted in different
species, we could advance our analysis by the point-to-
point relationship between temperature and species,
from which the PB2 proteins were sampled. Figure 4
demonstrated the trends of PB2 evolution with respect to
the temperature in three major species. The results sug-
gested that the trends were similar in human and swine,
but different in avian. 4. ACKNOWLEDGEMENTS
In this study, we found the similar trends in global
warming and the evolution of PB2 proteins from influ-
enza A viruses. This is very suggestive, because this
founding indicates that the effect of global warming on
many different levels on biological evolution, even the
proteins hidden inside cell could be subject to the global
warming. This is understandable because all of the bio-
logical functions are interconnected from macro level to
micro level.
This study is supported in part by Guangxi Science Foundation No.
0782003-4, 0991080 and Guangxi Academy of Sciences, project
09YJ17SW07.
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