Vol.
176,
No.
May
15, 1991
BIOCHEMICAL
3, 1991
AND
RESEARCH
COMMUNICATIONS Pages
EVOLUTIONARY George
T.
GROUPING
Drivas,
OF
Stephen and
February
28,
RAS-PROTEIN
Palmieri, G.
of
FAMILY
Peter
D'Eustachio
Rush
School
York,
1130-1135
Biochemistry,
University New
THE
Mark
Department York
New
Received
BIOPHYSICAL
New
of
York,
Medicine,
10016
1991
Over 50 proteins related to the mammalian H-, K-, and N-RAS GTP binding and hydrolyzing proteins are known. These relatively low molecular weight proteins are usually grouped into four subfamilies, termed true RAS, RAS-like, RHO, and RAB/YPT, based on the presence of shared amino acid sequence motifs in addition to those involved in guanine nucleotide binding. Here, we apply parsimony analysis to the overall amino acid sequences of these proteins to infer possible phylogenetic relationships among them. 0 1991 Academic Press, Inc.
The
RAS
overall ancestral both
true
1,3).
RAS), we
relationships
AND
I
reported)
were
and
devised
by be
trees proteins,
accumulation
Gene
Analysis true to
of
these
include of and
domains four
RHO
true
could
conversion
of into
RAS),
homology
have
generated and
to
of
conserved
subfamilies (about
RAS) to
termed
35%
(for
proteins
in
required
RAS
more 15
than
homology
reviews,
see
analyze
0006-291X/91 $1.50 Copyright 0 1991 by Academic Press. Inc. All rights of reproduction in any form reserved.
the
program
one
change
were
with
the
that
proteins respectively.
was Figures
then l-3
considered
of
amino
those acid
optimized PROTPARS
any
program
changes
of
amino
only nucleotide Thus if two proteins
recognizes at
seguencee and
75%
subfamily,
and considers substitutions.
shown),
1130
(about
(5)
insists
subfamily.
RAS-like
proteins,
analysis
representative
not each
and
acid
position,
each
program
program code,
amino
(data
RAB/YPT
parsimony
membere
For
GAP
genetic
acid
family
study. the
This
the
within for
fx
this
with
classified
sequences
RAS
in
result
subfamilies of
family
the
whose a common
subfamilies.
(6).
amino
reliably
recognized number
analyzed
with
given
a
may
program
the
subjected
that
difference
30%
representative
Felsenstein
consistent
at
of
the
as
well
family
to
sequences
generated
then
J.
substitutions differ
77
alignments
manually,
(about
all
lists
that
sequence
homology
entire
of
as
insertions. the
kd) from
history
possible. of
(20-30
evolution
DISCUSSION
Table
acids
the
within
RESULTS
50%
RAB/YPT
use
also
GTPases
suggest
and
division
(about
and
Here,
are allows
RAS-like
small
duplications, deletions,
sequence
RAS,
various sequences
evolutionary
recent
transmission
acid
for
acid
The
more
substitutions,
interspecies amino
codes amino
(1,2,3,4). and
nucleotide
to
family and
gene ancient
true
gene
structures
the
that
this
nucleotide into
used
to
show as
level.
the the
The
four
analyze
a larger
parsimony
a group,
for
RliO
Vol.
176,
No.
BIOCHEMICAL
3, 1991
AND
BIOPHYSICAL
Table
RESEARCH
COMMUNICATIONS
I
RAS GENE FAMILY I.
&B
subfamily
As-rae Dm-raal Xl-ram Fi-r-as II.
(9) 1::;
Rag-like
(20) (21) (22) (23) (20)
Bo-smg2la
Hu-raplb Bo-smg2lb Hu-rap2a Rho
Hu-ralB Dm-ras2 Mu-Rras Hu-Rrae Hu-TC21
(28) (29) (30) (30) (31)
Ca-rho1 Hu-rhoA Hu-rhoB Hu-rhoC
(33) (39) (40) (40)
Ca-rabl0 Ca-rab8 SP-YPt2 Dd-sasl Dd-sas2 SC-SEC4 Bo-smg25C(56) Bo-•mg25B(56) Hu-rab3b Bo-•mg25A(56) Ra-rab3 Hu-rab3a
(33) (33) (53) (54) (54) (55)
y;
-
Hu-rap2b Dm-ras3 ;z;-';'
(24) (25)
(26)
(27) (28)
Hu-ralA
subfamily
Hu-racl Ca-racl Hu-rac2 Hu-en7 Hu-TClO IV.
(17) (18)
subfamily
Hu-rapla
III.
;y;s
(12)
Dd-rasG sc-RASl
Hu-G25 SC-CDC42 sc-RHO2 SC-RHO1 Ap-rho
I::; Ii:; (31)
RablYPT
subfamily
Sc-Sarl Hu-TC4 Ca-rabl Ra-BRLras Sp-ryhl Hu-rab6 Ca-rab5 Hu-rab5 At-ara SP-YPt3 Ca-rabll Hu-YL8
Ca-rab4b
(33)
;:I;:;; Ra-rab2 Ca-tab2 Hu-tab2 SC-YPTl SP-YPtl Ra-rablb Mu-Yptl Ra-rabla Hu-rabl
;g ; (49) (42) (45) (50) (47) (51) (52) (49) (45)
(45) (49) (45)
1 to 3. References to aeguences are RAS-proteins analyzed in Figs. in parentheses. The first two letters of each family member indicate the source of the protein. Hu, human; Bo, bovine; Dm, Drosophila melanogaster; Saccharomyces cerevisiae (yeast); So, Saguinus Oedipus (simian); As, Artemia salina (shrimp); Xl, Xenopus laevis (toad); Fi, fish; Dd, Dictyostelium discodium (slime mold); Sp, Schizosaccharomyces pombe, (yeast); Mu, murine; (mollusc); Ca, canine; Ra, rat; At, Arabidopsis thaliana (plant). AP, Aplysia
It
is
important
proportional
to
parsimony in
program
which
and/or
the
can
changes
phylogeny, are not
that
the and
branch have
in
some
cases,
the
branch
distance,
and
over
that
the
the
The
species
accurate
analysis.
different
species, need not
be In
such of
timo
change
in
homologous
performing
different
rates.
represent
groupings
with
essence,
which the phylogenetic
overall tree.
topologies
the the
a strong are
same
trees
RAS function
presented
bias close
towards to
1131
those
to
requires
that
a branch
branches assumed
the too
RAS
proteins here
the
great
from be
be
considered
a true
of such
an
two
m evolving
relationships, for
phylogeny for
the
may
should
amino
divergence
within thus
time
the
proteins
phylogenetic expected
few of
of
for
often
and
trees
proportional
in
different
are not This
phylogenetic
are
involved
times
these trees symmetrically.
construct
1 to 3 are in Figs. two highly homologous
addition, two highly
of
a construction
evolutionary
covered In or
to (nodes)
but of
lengths been drawn
points
lengths
rates
different.
biological
species,
time, used,
to
occur
very
note
be
distances
evolutionary
acid
the
to
evolutionary
SC,
at to in
Vol.
176,
No.
BIOCHEMICAL
3, 1991
AND
BIOPHYSICAL
RESEARCH
COMMUNICATIONS
Hu-rap2b
Hu-raplb/Ba-sm,?Zlb
, 68%
87% Fi-ras w
88% 95%
It-
Fia. 1. Comparison of P.&S and MS-like amino acid sequences. The Hu-MB1 sequence is included as an outlying related protein. In those cases where more than one protein is present on a line, they are either identical or exhibit at least 98% sequence identity. The percentages represent either the amino acid identity between two sequences, or the average amino acid identities among Since the parsimony program used to generate this tree more than one sequence. considers the minimum number of nucleotide changes consistent with a given amino acid change, the % amino acid identity alone does not determine the tree topology.
As previously noted, the expected complex evolutionary history of the and conversions) precludes PAS-gene family (involving duplications, mutations, any extensive non-epeculative interpretation of the data shown in Figs. 1 to 3. However, the following three points are worth noting: 1) the overall groupings are generally consistent with those expected on the basis of amino acid sequence homology; 2) certain closely grouped (paired) sequences within the same species such as Hu-rapla/Hu-raplb, Hu-rapZa/Hu-rapZb, Hu-ralA/Hu-ral8 (all in Fig. I), and Hu-racl/Hu-rac2, Hu-rhoA/Hu-rhoC (all in Fig. 2), probably reflect more recent gene duplications; and 3) certain closely grouped sequences between very different species such ae Sp-ypt3/Hu-YL8 and Hurabl/Sc-YPT1 (both in Fig. 3) probably represent interspecfes homologues performing similar if not identical functions. 1132
Vol.
176,
No.
BIOCHEMICAL
3, 1991
w. included details.
Comparison as an
of outlying
RHO
amino related
AND
BIOPHYSICAL
acid sequences. protein. See
The legend
RESEARCH
Hu-KRAS to Fig.
COMMUNICATIONS
sequence 1 for
is further
HwTC4 Ca-rab7iRa-BRLras I
I
I
I
I
I
I
P
Hu-YLS/Ca-rabll
Ra-rab4/Hu-rab4 Ca-rab2/Hu-rab2iRa-~b2
51% -
Ca-rabl0
8
Grab
.
61%-
6&Z-
5%
-
SC-SEC4
Bo-smgZB/Hu-rab3b
Fia. included details.
3.
Comparison as an outlying
80% -
of
RAE/YPT related
amino protein.
acid
1133
sequences. See legend
to
The Hu-KRAS Fig. 1 for
sequence further
is
Vol.
176,
No.
3,
1991
BIOCHEMICAL
AND
BIOPHYSICAL
RESEARCH
COMMUNICATIONS
The overall groupings presented in this communication should serve as a framework in which to place, tentatively, newly reported me&era of the family. Most members of the RAS and RAS-like subfamilies are now thought to mediate signal transduction and the regulation of cell growth, and most members of the RAB/YPT subfamily are thought to participate in vesicle sorting A common function of the RHO subfamily remains to (for references, see l-4). be established, but it may be related to the maintenance of cell structure (7,8).
ACKNOWLEDGMENTS We thank Elias Coutavas for many helpful discussions, and Lara Schulman and John Hill of the Research Computing Resource (RCR), Dept. of Cell Biology The RCR is supported by NSF grant for installing the PHYLIP phylogeny package. #DIR-8908095.
REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. E: 13. 14. 15.
Bourne, H.R., Sanders, D.A., and McCormick, F. (1991) Nature (London) 349:117-127. Bourne, H.R., Sanders, D.A., and McCormick, F. (1990) Nature (London) 348:125-132. Downward, J. (1990) Trends Biochem. Sci. 15:469-472. Balch, W.E. (1990) Trends Biochem. Sci. 15:473-476. Derereux, J., Haeberli, P. and Smithies, 0. (1984) Nucleic Acids Res. 12:387-395. PHYLIP Manual Version 3.3. University Felsenstein, J. (1990) Herbarium, University of California, Berkely, California. Chardin, P., Boguet, P., Maudale, P., Popoff, M.R.,Rubin, E.J., and Gill, D.M. (1989) EMBO J. 1087-1092. Paterson, H.F., Self, A.J., Garrett, M.D., Just, I.,Aktories, K., and Hall, A. (1990) J. Cell Biol. lll:lOOl-1007. Diaz-Guerra, M., Quintanilla, M., Palmero, I., Saetre, L.and Renart, J. (1989) Biochem. Biophys. Res. Commun. 162:802-808. Neumann-Silberberg, F.S., Schejter, E., Hoffmann, F.N. Shilo, B.Z. (1984) Cell 37:1027-1032. Andeol, Y., Gusse, M. and Hechali, H. (1990) Dev. Biol. 139:24-34. Nemoto, N., Kodama, K-I., Tazawa, A., Masahito, P., and Ishikawa, T. (1986) Differentiation 32:17-23. Capon, D.J., Chen, E.Y., Levinson, A.D., Seeburg, P.H. and Goeddel, D.V. (1983) Nature (London) 302:33-37. Shimuzu, K., Birnbaum, D., Ruley, M.A., Fasano, O., Suard, Y., Edlund, L., Taparowsky, E., Goldfarb, M. and Wigler, M. (1983) Nature (London) 304:497-500. Taparowsky, E., Shimuzu, K., Goldfarb, h. and Wigler, M. (1983) Cell 34:581-586.
16. 17. 18. 19.
20. 21. 22. 23. 24. 25.
Reymond, C.D., Gomer, R.H., Mehdy, M.C. and Firtel, R.A. (1984) Cell 39:141-148. Robbins, S.M., Williams, J.G., Jermyn, K-A., Spiegelman, G.B. and Weeks, G. (1989) Proc. N&l. Acad. Sci. USA. 86:938-942. Pow&s, is., Kataoka, T., Fasano, O., Goldfarb, M., Strathern, J., Broach, J. and Wigler, H. (1984) Cell 36:607-612. Fukui, Y. and Kaziro, Y. (1985) EMBO J. 4:687-691. Pizon, V., Chardin, P., Lerosey, I., Olofsson, B., and Tavitian, A. (1988) Oncogene 3:201-204. Kawata, M., Matsui, Y., Kondo, J., Hishida, T., Teranishi, Y., and Takai, Y. (1988) J. Biol.Chem. 263:18965-18971. Pizon; V.,‘I. Lerosey, P. Chardin, and Tavitian, A. (1988) Nucleic Acids Res. 16:7719. Hatsui, Y., Kikuchi, A., Kawata, M., Kondo, J., Teranishi, Y., and Takai, Y. (1990) Biochem. Biophys. Res. Comm.166:1010-1016. Ohmstede, C-A., Farrell, F.X., Reap, B.R., Clemetson, K.J. and Lapetina, E.G. (1990) Proc. Natl. Acad. Sci. USA 87:6527-6531. Schejter, E.D. and Shilo, B.S. (1985) EMBC J. 4:407-412. 1134
Vol.
26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. Z: 49. 50. 51. 52. 53. 54. 55. 56.
176,
No.
3, 1991
BIOCHEMICAL
AND
BIOPHYSICAL
RESEARCH
COMMUNICATIONS
Bender, A. and Pringle, J. (1990) Proc. Natl. Acad. Sci. USA 86:99769980. Chardin, P. and Tavitian, A. (1986) EMBO J. 5:2203-2208. Chardin, P. and Tavitian, A. (1989) Nucleic Acids Res. 17:4380. Mozer, B., Marlor, R., Parkhurst, S. and Corcea, V. (1985) Mol. Cell. Biol. 5:885-889. Lowe, D.G., Capon, D.J., Delwart, E., Sakaguchi, A.Y., Naylor, S.L. and Goeddel, D.V. (1987) Cell 48:137-146. Drivae, G.T., Shih, A., Coutavas, E., Rush, M.G. and D'Eustachio, P.(1990) Hol. Cell. Biol. 10:1793-1798. D&bury, J., Weber, R.F., Bokoch, G.M., Evans, T. and Snyderman, R. (1989) J. Biol. Chem. 264:16378-16382. Chavrier, P., Vingron, M., Sander, C., Simons, K. and Zerial, M. (1990) Mol. Cell. Biol. 10:6578-6585. Shireat, N.V., Pignolo, R.J., Kreider, B.L. and Rovera, G. (1990) Oncogene 5:769-772. Munemitsu, S., fnnis, M.A., Clark, R., McCormick, F., Ullrich, A. and Polakis, P. (1990) Mol. Cell. Biol. 10:5977-5982. Johnson, D.I. and Pringle, J.R.. (1990) J. Cell Biol. 111:143-152. Madaule, P., Axel, R. and Myers, A.M. (19P7) Proc. Natl. Acad. Sci. USA 848779-783. Madaule, P. and Axel, R. (1985) Cell 41:31-40. Yeremian, P., Chardin, P., Hadaule, P. and Tavitian, A. (1987) Nucleic Acids Res. 15: 1869. Chardin, P., Maudale, P. and Tavitian, A. (1988) Nucleic Acids Res. 16:2717. Nakano, A. and Maramatsu, M. (1989) J. Cell Biol. 109:26772691. Chavrier, P., Parton, R.G., Hauri, H.P., Simons, K. and Serial, M. (1990) Cell 62:317-329. Bucci, C., Frunzio, R., Chiariotti, L., Brown, A.L., Rechler, H.M. and Bruni, C.B. (1988) Nucleic Acids Res. 16:9979-9986. Hengst, L. Lehmeier, T. and Gallwitz, D. (1990) EMBO J. 9:1949-1955. Zahraoui. A., Touchot. N.. Chardin. P. and Tavitian. A. (1989) J. Biol. Chem. 264:12394-12401; . Matsui, M., Sasamoto, S., Kunieda, T., Nomura, N. and Shizaki, R. (1989) Gene 76:313-319. Miyake, S. and Yamamoto, M. (1990) EMBO J. 9:1417-1422. Drivas, G.T., Shih, A., Coutavas, E-E., D'Eustachio, P. and Rush, M.G. (1991) Gncogene 6:3-9. Touchot, N., Chardin, P. and Tavitian, A. (1987) Proc. Natl. Acad. Sci. USA 84:8210-8214. Gallwitz, D., Donath, C. and Sander, C. (1983) Nature 306:704-707. Vielh, E., Touchot, N., Zahraoui, A. and Tavitian, A. (1989) Nucleic Acids Res. 17:1770. Haubruck, H., Disela, C., Wagner, P. and Gallwitz, D. (1987) EMBO J. 6:4049-4053. Haubruck, H., Engelke, U., Mertins, P. and Gallwitz, D. (1990) EMBO J. 9:1957-1962. Saxe, S.A. and Kimmel, A.R. (1990) Mol. Cell. Biol. 10:2367-2378. P.J. (1987) Cell 49:527-538. Salminen, A. and Novick, Matsui, Y. Kikuchi, A., Kondo, J., Hishida, T., Teranishi, Y. and Takai, Y. (1988) J. Biol. Chem. 263:11071-11074.
1135
176,
No.
May
15, 1991
BIOCHEMICAL
3, 1991
AND
RESEARCH
COMMUNICATIONS Pages
EVOLUTIONARY George
T.
GROUPING
Drivas,
OF
Stephen and
February
28,
RAS-PROTEIN
Palmieri, G.
of
FAMILY
Peter
D'Eustachio
Rush
School
York,
1130-1135
Biochemistry,
University New
THE
Mark
Department York
New
Received
BIOPHYSICAL
New
of
York,
Medicine,
10016
1991
Over 50 proteins related to the mammalian H-, K-, and N-RAS GTP binding and hydrolyzing proteins are known. These relatively low molecular weight proteins are usually grouped into four subfamilies, termed true RAS, RAS-like, RHO, and RAB/YPT, based on the presence of shared amino acid sequence motifs in addition to those involved in guanine nucleotide binding. Here, we apply parsimony analysis to the overall amino acid sequences of these proteins to infer possible phylogenetic relationships among them. 0 1991 Academic Press, Inc.
The
RAS
overall ancestral both
true
1,3).
RAS), we
relationships
AND
I
reported)
were
and
devised
by be
trees proteins,
accumulation
Gene
Analysis true to
of
these
include of and
domains four
RHO
true
could
conversion
of into
RAS),
homology
have
generated and
to
of
conserved
subfamilies (about
RAS) to
termed
35%
(for
proteins
in
required
RAS
more 15
than
homology
reviews,
see
analyze
0006-291X/91 $1.50 Copyright 0 1991 by Academic Press. Inc. All rights of reproduction in any form reserved.
the
program
one
change
were
with
the
that
proteins respectively.
was Figures
then l-3
considered
of
amino
those acid
optimized PROTPARS
any
program
changes
of
amino
only nucleotide Thus if two proteins
recognizes at
seguencee and
75%
subfamily,
and considers substitutions.
shown),
1130
(about
(5)
insists
subfamily.
RAS-like
proteins,
analysis
representative
not each
and
acid
position,
each
program
program code,
amino
(data
RAB/YPT
parsimony
membere
For
GAP
genetic
acid
family
study. the
This
the
within for
fx
this
with
classified
sequences
RAS
in
result
subfamilies of
family
the
whose a common
subfamilies.
(6).
amino
reliably
recognized number
analyzed
with
given
a
may
program
the
subjected
that
difference
30%
representative
Felsenstein
consistent
at
of
the
as
well
family
to
sequences
generated
then
J.
substitutions differ
77
alignments
manually,
(about
all
lists
that
sequence
homology
entire
of
as
insertions. the
kd) from
history
possible. of
(20-30
evolution
DISCUSSION
Table
acids
the
within
RESULTS
50%
RAB/YPT
use
also
GTPases
suggest
and
division
(about
and
Here,
are allows
RAS-like
small
duplications, deletions,
sequence
RAS,
various sequences
evolutionary
recent
transmission
acid
for
acid
The
more
substitutions,
interspecies amino
codes amino
(1,2,3,4). and
nucleotide
to
family and
gene ancient
true
gene
structures
the
that
this
nucleotide into
used
to
show as
level.
the the
The
four
analyze
a larger
parsimony
a group,
for
RliO
Vol.
176,
No.
BIOCHEMICAL
3, 1991
AND
BIOPHYSICAL
Table
RESEARCH
COMMUNICATIONS
I
RAS GENE FAMILY I.
&B
subfamily
As-rae Dm-raal Xl-ram Fi-r-as II.
(9) 1::;
Rag-like
(20) (21) (22) (23) (20)
Bo-smg2la
Hu-raplb Bo-smg2lb Hu-rap2a Rho
Hu-ralB Dm-ras2 Mu-Rras Hu-Rrae Hu-TC21
(28) (29) (30) (30) (31)
Ca-rho1 Hu-rhoA Hu-rhoB Hu-rhoC
(33) (39) (40) (40)
Ca-rabl0 Ca-rab8 SP-YPt2 Dd-sasl Dd-sas2 SC-SEC4 Bo-smg25C(56) Bo-•mg25B(56) Hu-rab3b Bo-•mg25A(56) Ra-rab3 Hu-rab3a
(33) (33) (53) (54) (54) (55)
y;
-
Hu-rap2b Dm-ras3 ;z;-';'
(24) (25)
(26)
(27) (28)
Hu-ralA
subfamily
Hu-racl Ca-racl Hu-rac2 Hu-en7 Hu-TClO IV.
(17) (18)
subfamily
Hu-rapla
III.
;y;s
(12)
Dd-rasG sc-RASl
Hu-G25 SC-CDC42 sc-RHO2 SC-RHO1 Ap-rho
I::; Ii:; (31)
RablYPT
subfamily
Sc-Sarl Hu-TC4 Ca-rabl Ra-BRLras Sp-ryhl Hu-rab6 Ca-rab5 Hu-rab5 At-ara SP-YPt3 Ca-rabll Hu-YL8
Ca-rab4b
(33)
;:I;:;; Ra-rab2 Ca-tab2 Hu-tab2 SC-YPTl SP-YPtl Ra-rablb Mu-Yptl Ra-rabla Hu-rabl
;g ; (49) (42) (45) (50) (47) (51) (52) (49) (45)
(45) (49) (45)
1 to 3. References to aeguences are RAS-proteins analyzed in Figs. in parentheses. The first two letters of each family member indicate the source of the protein. Hu, human; Bo, bovine; Dm, Drosophila melanogaster; Saccharomyces cerevisiae (yeast); So, Saguinus Oedipus (simian); As, Artemia salina (shrimp); Xl, Xenopus laevis (toad); Fi, fish; Dd, Dictyostelium discodium (slime mold); Sp, Schizosaccharomyces pombe, (yeast); Mu, murine; (mollusc); Ca, canine; Ra, rat; At, Arabidopsis thaliana (plant). AP, Aplysia
It
is
important
proportional
to
parsimony in
program
which
and/or
the
can
changes
phylogeny, are not
that
the and
branch have
in
some
cases,
the
branch
distance,
and
over
that
the
the
The
species
accurate
analysis.
different
species, need not
be In
such of
timo
change
in
homologous
performing
different
rates.
represent
groupings
with
essence,
which the phylogenetic
overall tree.
topologies
the the
a strong are
same
trees
RAS function
presented
bias close
towards to
1131
those
to
requires
that
a branch
branches assumed
the too
RAS
proteins here
the
great
from be
be
considered
a true
of such
an
two
m evolving
relationships, for
phylogeny for
the
may
should
amino
divergence
within thus
time
the
proteins
phylogenetic expected
few of
of
for
often
and
trees
proportional
in
different
are not This
phylogenetic
are
involved
times
these trees symmetrically.
construct
1 to 3 are in Figs. two highly homologous
addition, two highly
of
a construction
evolutionary
covered In or
to (nodes)
but of
lengths been drawn
points
lengths
rates
different.
biological
species,
time, used,
to
occur
very
note
be
distances
evolutionary
acid
the
to
evolutionary
SC,
at to in
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Hu-rap2b
Hu-raplb/Ba-sm,?Zlb
, 68%
87% Fi-ras w
88% 95%
It-
Fia. 1. Comparison of P.&S and MS-like amino acid sequences. The Hu-MB1 sequence is included as an outlying related protein. In those cases where more than one protein is present on a line, they are either identical or exhibit at least 98% sequence identity. The percentages represent either the amino acid identity between two sequences, or the average amino acid identities among Since the parsimony program used to generate this tree more than one sequence. considers the minimum number of nucleotide changes consistent with a given amino acid change, the % amino acid identity alone does not determine the tree topology.
As previously noted, the expected complex evolutionary history of the and conversions) precludes PAS-gene family (involving duplications, mutations, any extensive non-epeculative interpretation of the data shown in Figs. 1 to 3. However, the following three points are worth noting: 1) the overall groupings are generally consistent with those expected on the basis of amino acid sequence homology; 2) certain closely grouped (paired) sequences within the same species such as Hu-rapla/Hu-raplb, Hu-rapZa/Hu-rapZb, Hu-ralA/Hu-ral8 (all in Fig. I), and Hu-racl/Hu-rac2, Hu-rhoA/Hu-rhoC (all in Fig. 2), probably reflect more recent gene duplications; and 3) certain closely grouped sequences between very different species such ae Sp-ypt3/Hu-YL8 and Hurabl/Sc-YPT1 (both in Fig. 3) probably represent interspecfes homologues performing similar if not identical functions. 1132
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w. included details.
Comparison as an
of outlying
RHO
amino related
AND
BIOPHYSICAL
acid sequences. protein. See
The legend
RESEARCH
Hu-KRAS to Fig.
COMMUNICATIONS
sequence 1 for
is further
HwTC4 Ca-rab7iRa-BRLras I
I
I
I
I
I
I
P
Hu-YLS/Ca-rabll
Ra-rab4/Hu-rab4 Ca-rab2/Hu-rab2iRa-~b2
51% -
Ca-rabl0
8
Grab
.
61%-
6&Z-
5%
-
SC-SEC4
Bo-smgZB/Hu-rab3b
Fia. included details.
3.
Comparison as an outlying
80% -
of
RAE/YPT related
amino protein.
acid
1133
sequences. See legend
to
The Hu-KRAS Fig. 1 for
sequence further
is
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The overall groupings presented in this communication should serve as a framework in which to place, tentatively, newly reported me&era of the family. Most members of the RAS and RAS-like subfamilies are now thought to mediate signal transduction and the regulation of cell growth, and most members of the RAB/YPT subfamily are thought to participate in vesicle sorting A common function of the RHO subfamily remains to (for references, see l-4). be established, but it may be related to the maintenance of cell structure (7,8).
ACKNOWLEDGMENTS We thank Elias Coutavas for many helpful discussions, and Lara Schulman and John Hill of the Research Computing Resource (RCR), Dept. of Cell Biology The RCR is supported by NSF grant for installing the PHYLIP phylogeny package. #DIR-8908095.
REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. E: 13. 14. 15.
Bourne, H.R., Sanders, D.A., and McCormick, F. (1991) Nature (London) 349:117-127. Bourne, H.R., Sanders, D.A., and McCormick, F. (1990) Nature (London) 348:125-132. Downward, J. (1990) Trends Biochem. Sci. 15:469-472. Balch, W.E. (1990) Trends Biochem. Sci. 15:473-476. Derereux, J., Haeberli, P. and Smithies, 0. (1984) Nucleic Acids Res. 12:387-395. PHYLIP Manual Version 3.3. University Felsenstein, J. (1990) Herbarium, University of California, Berkely, California. Chardin, P., Boguet, P., Maudale, P., Popoff, M.R.,Rubin, E.J., and Gill, D.M. (1989) EMBO J. 1087-1092. Paterson, H.F., Self, A.J., Garrett, M.D., Just, I.,Aktories, K., and Hall, A. (1990) J. Cell Biol. lll:lOOl-1007. Diaz-Guerra, M., Quintanilla, M., Palmero, I., Saetre, L.and Renart, J. (1989) Biochem. Biophys. Res. Commun. 162:802-808. Neumann-Silberberg, F.S., Schejter, E., Hoffmann, F.N. Shilo, B.Z. (1984) Cell 37:1027-1032. Andeol, Y., Gusse, M. and Hechali, H. (1990) Dev. Biol. 139:24-34. Nemoto, N., Kodama, K-I., Tazawa, A., Masahito, P., and Ishikawa, T. (1986) Differentiation 32:17-23. Capon, D.J., Chen, E.Y., Levinson, A.D., Seeburg, P.H. and Goeddel, D.V. (1983) Nature (London) 302:33-37. Shimuzu, K., Birnbaum, D., Ruley, M.A., Fasano, O., Suard, Y., Edlund, L., Taparowsky, E., Goldfarb, M. and Wigler, M. (1983) Nature (London) 304:497-500. Taparowsky, E., Shimuzu, K., Goldfarb, h. and Wigler, M. (1983) Cell 34:581-586.
16. 17. 18. 19.
20. 21. 22. 23. 24. 25.
Reymond, C.D., Gomer, R.H., Mehdy, M.C. and Firtel, R.A. (1984) Cell 39:141-148. Robbins, S.M., Williams, J.G., Jermyn, K-A., Spiegelman, G.B. and Weeks, G. (1989) Proc. N&l. Acad. Sci. USA. 86:938-942. Pow&s, is., Kataoka, T., Fasano, O., Goldfarb, M., Strathern, J., Broach, J. and Wigler, H. (1984) Cell 36:607-612. Fukui, Y. and Kaziro, Y. (1985) EMBO J. 4:687-691. Pizon, V., Chardin, P., Lerosey, I., Olofsson, B., and Tavitian, A. (1988) Oncogene 3:201-204. Kawata, M., Matsui, Y., Kondo, J., Hishida, T., Teranishi, Y., and Takai, Y. (1988) J. Biol.Chem. 263:18965-18971. Pizon; V.,‘I. Lerosey, P. Chardin, and Tavitian, A. (1988) Nucleic Acids Res. 16:7719. Hatsui, Y., Kikuchi, A., Kawata, M., Kondo, J., Teranishi, Y., and Takai, Y. (1990) Biochem. Biophys. Res. Comm.166:1010-1016. Ohmstede, C-A., Farrell, F.X., Reap, B.R., Clemetson, K.J. and Lapetina, E.G. (1990) Proc. Natl. Acad. Sci. USA 87:6527-6531. Schejter, E.D. and Shilo, B.S. (1985) EMBC J. 4:407-412. 1134
Vol.
26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. Z: 49. 50. 51. 52. 53. 54. 55. 56.
176,
No.
3, 1991
BIOCHEMICAL
AND
BIOPHYSICAL
RESEARCH
COMMUNICATIONS
Bender, A. and Pringle, J. (1990) Proc. Natl. Acad. Sci. USA 86:99769980. Chardin, P. and Tavitian, A. (1986) EMBO J. 5:2203-2208. Chardin, P. and Tavitian, A. (1989) Nucleic Acids Res. 17:4380. Mozer, B., Marlor, R., Parkhurst, S. and Corcea, V. (1985) Mol. Cell. Biol. 5:885-889. Lowe, D.G., Capon, D.J., Delwart, E., Sakaguchi, A.Y., Naylor, S.L. and Goeddel, D.V. (1987) Cell 48:137-146. Drivae, G.T., Shih, A., Coutavas, E., Rush, M.G. and D'Eustachio, P.(1990) Hol. Cell. Biol. 10:1793-1798. D&bury, J., Weber, R.F., Bokoch, G.M., Evans, T. and Snyderman, R. (1989) J. Biol. Chem. 264:16378-16382. Chavrier, P., Vingron, M., Sander, C., Simons, K. and Zerial, M. (1990) Mol. Cell. Biol. 10:6578-6585. Shireat, N.V., Pignolo, R.J., Kreider, B.L. and Rovera, G. (1990) Oncogene 5:769-772. Munemitsu, S., fnnis, M.A., Clark, R., McCormick, F., Ullrich, A. and Polakis, P. (1990) Mol. Cell. Biol. 10:5977-5982. Johnson, D.I. and Pringle, J.R.. (1990) J. Cell Biol. 111:143-152. Madaule, P., Axel, R. and Myers, A.M. (19P7) Proc. Natl. Acad. Sci. USA 848779-783. Madaule, P. and Axel, R. (1985) Cell 41:31-40. Yeremian, P., Chardin, P., Hadaule, P. and Tavitian, A. (1987) Nucleic Acids Res. 15: 1869. Chardin, P., Maudale, P. and Tavitian, A. (1988) Nucleic Acids Res. 16:2717. Nakano, A. and Maramatsu, M. (1989) J. Cell Biol. 109:26772691. Chavrier, P., Parton, R.G., Hauri, H.P., Simons, K. and Serial, M. (1990) Cell 62:317-329. Bucci, C., Frunzio, R., Chiariotti, L., Brown, A.L., Rechler, H.M. and Bruni, C.B. (1988) Nucleic Acids Res. 16:9979-9986. Hengst, L. Lehmeier, T. and Gallwitz, D. (1990) EMBO J. 9:1949-1955. Zahraoui. A., Touchot. N.. Chardin. P. and Tavitian. A. (1989) J. Biol. Chem. 264:12394-12401; . Matsui, M., Sasamoto, S., Kunieda, T., Nomura, N. and Shizaki, R. (1989) Gene 76:313-319. Miyake, S. and Yamamoto, M. (1990) EMBO J. 9:1417-1422. Drivas, G.T., Shih, A., Coutavas, E-E., D'Eustachio, P. and Rush, M.G. (1991) Gncogene 6:3-9. Touchot, N., Chardin, P. and Tavitian, A. (1987) Proc. Natl. Acad. Sci. USA 84:8210-8214. Gallwitz, D., Donath, C. and Sander, C. (1983) Nature 306:704-707. Vielh, E., Touchot, N., Zahraoui, A. and Tavitian, A. (1989) Nucleic Acids Res. 17:1770. Haubruck, H., Disela, C., Wagner, P. and Gallwitz, D. (1987) EMBO J. 6:4049-4053. Haubruck, H., Engelke, U., Mertins, P. and Gallwitz, D. (1990) EMBO J. 9:1957-1962. Saxe, S.A. and Kimmel, A.R. (1990) Mol. Cell. Biol. 10:2367-2378. P.J. (1987) Cell 49:527-538. Salminen, A. and Novick, Matsui, Y. Kikuchi, A., Kondo, J., Hishida, T., Teranishi, Y. and Takai, Y. (1988) J. Biol. Chem. 263:11071-11074.
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