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Michael L. Yuan, Ian J. Wang
Sodium ion channel alkaloid resistance does not vary with toxicity in aposematic Dendrobates poison frogs: An examination of correlated trait evolution
www.plosone.org
www.plosone.org
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0.83 0.64 0.02 0 k
(31)Tj
0 g
(].)Tj
4.7225 0 Td
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2.4718 0 Td
(variation)Tj
3.804 0 Td
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-34.5427 -1.2983 Td
(toxin)Tj
2.3073 0 Td
(exposure)Tj
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2.2848 0 Td
(leads)Tj
2.211 0 Td
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(tradeoffs.)Tj
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4.8131 0 Td
(well)Tj
1.8199 0 Td
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(which)Tj
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(target)Tj
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(the)Tj
1.4684 0 Td
(pore)Tj
2.0409 0 Td
(of)Tj
1.0148 0 Td
(voltage-gated)Tj
5.5502 0 Td
(sodium)Tj
-34.5314 -1.2983 Td
(ion)Tj
1.542 0 Td
(channels)Tj
3.7304 0 Td
(\(Na)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 267.874 458.759 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(V)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 273.033 460.4031 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(s\)[)Tj
0.83 0.64 0.02 0 k
(17)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(32)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(33)Tj
0 g
(].)Tj
5.1363 0 Td
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4.9889 0 Td
(of)Tj
1.0148 0 Td
(softshell)Tj
3.481 0 Td
(clams,)Tj
/F13 1 Tf
2.7269 0 Td
[(\r)47()3()]TJ
2.0126 0 Td
[()16(\n)20()2()6()16(\n)-9()4()]TJ
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(,)Tj
3.8154 0 Td
(repeatedly)Tj
-30.4779 -1.2982 Td
(exposed)Tj
3.4413 0 Td
(to)Tj
1.0261 0 Td
(saxitoxins)Tj
4.1952 0 Td
(\(STX\))Tj
2.6418 0 Td
(have)Tj
2.058 0 Td
(evolved)Tj
3.2598 0 Td
(resistance)Tj
4.1272 0 Td
(through)Tj
3.4469 0 Td
(a)Tj
0.652 0 Td
(single)Tj
2.5342 0 Td
(Na)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 485.5181 445.7196 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(V)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 492.9448 447.4204 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(amino)Tj
2.7949 0 Td
(acid)Tj
1.8708 0 Td
(replace-)Tj
-33.9587 -1.3039 Td
(ment)Tj
2.3074 0 Td
([)Tj
0.83 0.64 0.02 0 k
(34)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(35)Tj
0 g
(].)Tj
3.2541 0 Td
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4.0309 0 Td
(populations)Tj
4.9492 0 Td
(of)Tj
/F13 1 Tf
1.0148 0 Td
[()]TJ
/F7 1 Tf
(.)Tj
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1.0375 0 Td
[( )10()12(\n)-19()11()11()12()-4( )]TJ
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2.795 0 Td
(that)Tj
1.7744 0 Td
(prey)Tj
1.9899 0 Td
(upon)Tj
2.3188 0 Td
(highly)Tj
2.7099 0 Td
(tetrodotoxin)Tj
5.2383 0 Td
(\(TTX\))Tj
-33.4202 -1.2982 Td
(defended)Tj
/F13 1 Tf
3.9118 0 Td
[()97()16(\n)-9()4()13()6()]TJ
/F7 1 Tf
3.2882 0 Td
(newts)Tj
2.5341 0 Td
(have)Tj
2.058 0 Td
(independently)Tj
5.9754 0 Td
(evolved)Tj
3.2598 0 Td
(resistance)Tj
4.1329 0 Td
(at)Tj
0.9524 0 Td
(Na)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 472.8188 419.7543 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(V)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 480.1889 421.3984 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(paralogs)Tj
3.5602 0 Td
([)Tj
0.83 0.64 0.02 0 k
(9)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(24)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(30)Tj
0 g
(].)Tj
3.9515 0 Td
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-35.5291 -1.2982 Td
(populations)Tj
4.9492 0 Td
(exposed)Tj
3.447 0 Td
(to)Tj
1.0261 0 Td
(limited)Tj
3.0671 0 Td
(or)Tj
1.0998 0 Td
(no)Tj
1.2756 0 Td
(TTX,)Tj
2.3187 0 Td
(resistance)Tj
4.1329 0 Td
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0.8504 0 Td
(potentially)Tj
4.456 0 Td
(deleterious)Tj
4.5977 0 Td
(due)Tj
1.7008 0 Td
(to)Tj
1.0261 0 Td
(reduced)Tj
-33.9474 -1.3039 Td
(motor)Tj
2.7212 0 Td
(performance)Tj
5.3461 0 Td
(associated)Tj
4.2577 0 Td
(with)Tj
2.0012 0 Td
(TTX)Tj
2.092 0 Td
(resistance)Tj
4.1328 0 Td
([)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(24)Tj
0 g
(].)Tj
3.2542 0 Td
(Thus,)Tj
2.4718 0 Td
(population-level)Tj
6.735 0 Td
(variation)Tj
-33.012 -1.2983 Td
(in)Tj
1.0318 0 Td
(resistance)Tj
4.1329 0 Td
(alleles)Tj
2.6022 0 Td
(throughout)Tj
4.7792 0 Td
(the)Tj
1.4683 0 Td
(range)Tj
2.4604 0 Td
(of)Tj
/F13 1 Tf
1.0148 0 Td
[()]TJ
/F7 1 Tf
(.)Tj
/F13 1 Tf
1.0375 0 Td
[( )10()12(\n)-19()11()11()12()-4( )]TJ
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2.795 0 Td
(positively)Tj
4.0195 0 Td
(covaries)Tj
3.4581 0 Td
(with)Tj
2.0013 0 Td
(prey)Tj
1.9842 0 Td
(toxicity)Tj
3.2031 0 Td
(lev-)Tj
-35.9883 -1.2983 Td
(els)Tj
1.2472 0 Td
([)Tj
0.83 0.64 0.02 0 k
(5)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(9)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(].)Tj
-0.051 -1.2982 Td
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2.9707 0 Td
(frogs)Tj
2.211 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(family)Tj
2.7326 0 Td
(Dendrobatidae)Tj
6.2248 0 Td
(have)Tj
2.058 0 Td
(repeatedly)Tj
4.3426 0 Td
(evolved)Tj
3.2542 0 Td
(the)Tj
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(capacity)Tj
3.4696 0 Td
(to)Tj
1.0261 0 Td
(sequester)Tj
-33.4655 -1.3039 Td
(alkaloid)Tj
3.3789 0 Td
(toxins)Tj
2.6645 0 Td
(from)Tj
2.2054 0 Td
(their)Tj
2.1089 0 Td
(diets)Tj
2.0976 0 Td
(into)Tj
1.8426 0 Td
(specialized)Tj
4.524 0 Td
(skin)Tj
1.8935 0 Td
(glands)Tj
2.8007 0 Td
(for)Tj
1.3889 0 Td
(chemical)Tj
3.7813 0 Td
(defense)Tj
3.2145 0 Td
([)Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(36)Tj
0 g
(].)Tj
3.2541 0 Td
(Three)Tj
-35.1549 -1.2983 Td
(major)Tj
2.6078 0 Td
(classes)Tj
2.829 0 Td
(of)Tj
1.0148 0 Td
(alkaloids)Tj
3.7417 0 Td
(found)Tj
2.6192 0 Td
(in)Tj
1.0318 0 Td
(poison)Tj
2.931 0 Td
(frogs)Tj
2.211 0 Td
(target)Tj
2.5115 0 Td
(Na)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 426.6708 328.7622 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(V)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 434.0976 330.4062 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(channels:)Tj
3.9571 0 Td
(batrachotoxins)Tj
6.1681 0 Td
(\(BTX\),)Tj
-33.5335 -1.2982 Td
(histrionicotoxins)Tj
7.0129 0 Td
(\(HTX\),)Tj
3.1577 0 Td
(and)Tj
1.7292 0 Td
(pumiliotoxins/allopumiliotox)Tj
11.7862 0 Td
(ins)Tj
1.3947 0 Td
(\(PTX/aPTX\)[)Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(].)Tj
7.1659 0 Td
(The)Tj
1.7802 0 Td
(utiliza-)Tj
-34.0268 -1.3039 Td
(tion)Tj
1.8425 0 Td
(of)Tj
1.0148 0 Td
(dietary)Tj
2.9934 0 Td
(alkaloids)Tj
3.7417 0 Td
(as)Tj
1.0148 0 Td
(chemical)Tj
3.7814 0 Td
(defense)Tj
3.2201 0 Td
(requires)Tj
3.4696 0 Td
(the)Tj
1.4683 0 Td
(congruent)Tj
4.3369 0 Td
(evolution)Tj
3.9968 0 Td
(of)Tj
1.0148 0 Td
(resistance)Tj
4.1329 0 Td
(to)Tj
-36.028 -1.2983 Td
(toxins)Tj
2.6645 0 Td
(from)Tj
2.2054 0 Td
(prey)Tj
1.9899 0 Td
(and)Tj
1.7291 0 Td
(autoresistance)Tj
5.896 0 Td
(to)Tj
1.0262 0 Td
(a)Tj
0.6576 0 Td
(species')Tj
3.2088 0 Td
(own)Tj
1.9616 0 Td
(toxins)Tj
2.6644 0 Td
(once)Tj
2.126 0 Td
(sequestered)Tj
4.8642 0 Td
([)Tj
0.83 0.64 0.02 0 k
(15)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(19)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(37)Tj
0 g
(].)Tj
4.4334 0 Td
(Sev-)Tj
-35.4271 -1.2983 Td
(eral)Tj
1.6951 0 Td
(lineages)Tj
3.3902 0 Td
(of)Tj
1.0148 0 Td
(poison)Tj
2.9253 0 Td
(frog)Tj
1.8539 0 Td
(have)Tj
2.0579 0 Td
(convergently)Tj
5.3858 0 Td
(evolved)Tj
3.2542 0 Td
(resistance)Tj
4.1328 0 Td
(to)Tj
1.0261 0 Td
(alkaloid)Tj
3.3789 0 Td
(toxins)Tj
2.6645 0 Td
(in)Tj
1.0375 0 Td
(at)Tj
0.9524 0 Td
(least)Tj
-34.7694 -1.3039 Td
(one)Tj
1.6951 0 Td
(sodium)Tj
3.2315 0 Td
(ion)Tj
1.542 0 Td
(channel,)Tj
3.6 0 Td
(Na)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 312.3779 263.7354 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(V)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 317.5937 265.3795 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(1.4,)Tj
1.6214 0 Td
(in)Tj
1.0374 0 Td
(congruence)Tj
4.8813 0 Td
(with)Tj
1.9955 0 Td
(alkaloids)Tj
3.7417 0 Td
(as)Tj
1.0148 0 Td
(chemical)Tj
3.7871 0 Td
(defense)Tj
3.2145 0 Td
([)Tj
0.83 0.64 0.02 0 k
(38)Tj
0 g
(].)Tj
-33.0517 -1.2982 Td
(Encoded)Tj
3.7474 0 Td
(by)Tj
1.1792 0 Td
(the)Tj
/F13 1 Tf
1.4683 0 Td
[()]TJ
/F7 1 Tf
3.1125 0 Td
(gene,)Tj
2.3072 0 Td
(Na)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 329.8393 250.7527 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(V)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 335.0551 252.3968 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(1.4)Tj
1.3946 0 Td
(is)Tj
0.8504 0 Td
(one)Tj
1.6951 0 Td
(of)Tj
1.0148 0 Td
(six)Tj
1.3152 0 Td
(Na)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 409.4362 250.7527 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(V)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 416.8629 252.3968 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(paralogs)Tj
3.5546 0 Td
(in)Tj
1.0374 0 Td
(amphibians)Tj
4.904 0 Td
([)Tj
0.83 0.64 0.02 0 k
(39)Tj
0 g
(].)Tj
2.0749 0 Td
(Whereas)Tj
-33.2558 -1.2982 Td
(several)Tj
2.9311 0 Td
(Na)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 241.0582 237.7133 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(V)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 248.4283 239.4141 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(paralogs)Tj
3.5546 0 Td
(are)Tj
1.4513 0 Td
(only)Tj
1.9786 0 Td
(expressed)Tj
4.0932 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(central)Tj
2.965 0 Td
(nervous)Tj
3.4129 0 Td
(system)Tj
2.9367 0 Td
(and)Tj
1.7291 0 Td
(thus)Tj
1.9389 0 Td
(protected)Tj
4.0081 0 Td
(from)Tj
-35.4157 -1.3039 Td
(many)Tj
2.4775 0 Td
(alkaloid)Tj
3.3787 0 Td
(toxins)Tj
2.6646 0 Td
(that)Tj
1.7801 0 Td
(might)Tj
2.5966 0 Td
(otherwise)Tj
4.0818 0 Td
(interact)Tj
3.2882 0 Td
(with)Tj
1.9956 0 Td
(them)Tj
2.2904 0 Td
(by)Tj
1.1792 0 Td
(the)Tj
1.474 0 Td
(blood-brain)Tj
4.9889 0 Td
(barrier,)Tj
-32.1956 -1.2982 Td
(Na)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 211.6913 211.748 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(V)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 216.907 213.3921 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(1.4)Tj
1.3946 0 Td
(is)Tj
0.8504 0 Td
(readily)Tj
2.9423 0 Td
(exposed)Tj
3.4469 0 Td
(to)Tj
1.0262 0 Td
(all)Tj
1.1452 0 Td
(sequestered)Tj
4.8698 0 Td
(toxins)Tj
2.6646 0 Td
(due)Tj
1.7008 0 Td
(to)Tj
1.0261 0 Td
(its)Tj
1.1452 0 Td
(expression)Tj
4.4617 0 Td
(in)Tj
1.0375 0 Td
(skeletal)Tj
3.1521 0 Td
(muscle)Tj
3.0217 0 Td
(tis-)Tj
-35.5745 -1.2982 Td
(sues)Tj
1.8934 0 Td
([)Tj
0.83 0.64 0.02 0 k
(30)Tj
0 g
(].)Tj
2.075 0 Td
(Previous)Tj
3.6907 0 Td
(work)Tj
2.279 0 Td
(has)Tj
1.5421 0 Td
(identified)Tj
4.0591 0 Td
(two)Tj
1.7122 0 Td
(amino)Tj
2.7949 0 Td
(acid)Tj
1.8709 0 Td
(replacements,)Tj
5.7372 0 Td
(A446D)Tj
3.0671 0 Td
(and)Tj
1.7291 0 Td
(I433V)Tj
2.6816 0 Td
()Tj
-35.1323 -1.2983 Td
(occurring)Tj
4.1158 0 Td
(in)Tj
1.0261 0 Td
(Domain)Tj
3.5263 0 Td
(I)Tj
0.5556 0 Td
(Subunit)Tj
3.3619 0 Td
(6)Tj
0.6859 0 Td
(\(DI-S6\),)Tj
3.498 0 Td
(which)Tj
2.6418 0 Td
(forms)Tj
2.5625 0 Td
(part)Tj
1.8312 0 Td
(of)Tj
1.0091 0 Td
(the)Tj
1.457 0 Td
(Na)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 474.4629 185.7259 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(V)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 479.6787 187.4267 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(1.4)Tj
1.3889 0 Td
(pore)Tj
2.0296 0 Td
(regionassoci-)Tj
-31.3849 -1.3039 Td
(ated)Tj
1.9049 0 Td
(with)Tj
1.9956 0 Td
(alkaloid)Tj
3.3788 0 Td
(resistance)Tj
4.1329 0 Td
(in)Tj
/F13 1 Tf
1.0318 0 Td
[()-6()2()6()12(\n)20()13()4()22()11()8( )]TJ
/F7 1 Tf
5.142 0 Td
([)Tj
0.83 0.64 0.02 0 k
(38)Tj
0 g
(].)Tj
2.075 0 Td
(Following)Tj
4.2179 0 Td
(Tarvin)Tj
2.9083 0 Td
(et)Tj
0.9411 0 Td
(al.)Tj
1.1281 0 Td
([)Tj
0.83 0.64 0.02 0 k
(38)Tj
0 g
(],)Tj
2.075 0 Td
(we)Tj
1.3266 0 Td
(refer)Tj
2.0976 0 Td
(to)Tj
-34.3556 -1.2982 Td
(amino)Tj
2.795 0 Td
(acids)Tj
2.2336 0 Td
(by)Tj
1.1792 0 Td
(their)Tj
2.109 0 Td
(homologous)Tj
5.1987 0 Td
(position)Tj
3.4923 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
/F13 1 Tf
1.474 0 Td
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(relative)Tj
3.1408 0 Td
(to)Tj
1.0204 0 Td
(higher)Tj
2.8063 0 Td
(toxicity)Tj
3.2031 0 Td
(populations)Tj
4.9493 0 Td
(in)Tj
1.0375 0 Td
(three)Tj
-34.6902 -1.2983 Td
(species)Tj
2.9934 0 Td
(of)Tj
/F13 1 Tf
1.0148 0 Td
[()-6()2()6()12(\n)20()13()4()22()11()8( )]TJ
/F7 1 Tf
(:)Tj
/F13 1 Tf
5.3688 0 Td
[()]TJ
/F7 1 Tf
(.)Tj
/F13 1 Tf
1.1395 0 Td
[()11()12()18()4()12()4()]TJ
/F7 1 Tf
(,)Tj
/F13 1 Tf
3.4582 0 Td
[()]TJ
/F7 1 Tf
(.)Tj
/F13 1 Tf
1.1395 0 Td
[()-8(\n)20()16()18()4()12()12()9()2(\n)-9()-4( )]TJ
/F7 1 Tf
(,)Tj
5.1421 0 Td
(and)Tj
/F13 1 Tf
1.7291 0 Td
[()]TJ
/F7 1 Tf
(.)Tj
/F13 1 Tf
1.1452 0 Td
[()16()12(\n)20()22()7()-4( )]TJ
/F7 1 Tf
(,)Tj
3.4582 0 Td
(focusing)Tj
3.6113 0 Td
(on)Tj
1.2756 0 Td
(two)Tj
1.7065 0 Td
(ecolog-)Tj
-33.1822 -1.3039 Td
(ically)Tj
2.2904 0 Td
(important)Tj
4.2803 0 Td
(substitutions)Tj
5.3517 0 Td
(\(A446D)Tj
3.4073 0 Td
(and)Tj
1.7291 0 Td
(I433V\))Tj
3.0217 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
/F13 1 Tf
1.4683 0 Td
[()]TJ
/F7 1 Tf
3.1068 0 Td
(gene)Tj
2.0806 0 Td
(that)Tj
1.7801 0 Td
(confer)Tj
2.7836 0 Td
(resistance)Tj
4.1328 0 Td
(to)Tj
-36.4702 -1.2983 Td
(alkaloid)Tj
3.3789 0 Td
(toxins)Tj
2.6645 0 Td
(in)Tj
1.0375 0 Td
(other)Tj
2.3471 0 Td
(dendrobatids)Tj
5.5218 0 Td
([)Tj
0.83 0.64 0.02 0 k
(38)Tj
0 g
(].)Tj
-13.7536 -1.2982 Td
(Several)Tj
3.0501 0 Td
(members)Tj
3.9458 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
/F13 1 Tf
1.4683 0 Td
[()18()-4( )9()7(\n)-9()4()11()18()4()1()-4( )]TJ
/F7 1 Tf
4.7395 0 Td
(group,)Tj
2.8346 0 Td
(including)Tj
/F13 1 Tf
4.0422 0 Td
[()]TJ
/F7 1 Tf
(.)Tj
/F13 1 Tf
1.1395 0 Td
[()11()12()18()4()12()4()]TJ
3.2372 0 Td
[()16()6()]TJ
1.7291 0 Td
[()]TJ
/F7 1 Tf
(.)Tj
/F13 1 Tf
1.1395 0 Td
[()-8(\n)20()16()18()4()12()12()9()2(\n)-9()-4( )]TJ
/F7 1 Tf
4.9153 0 Td
(\(=)Tj
/F13 1 Tf
1.1451 0 Td
[()]TJ
/F7 1 Tf
(.)Tj
/F13 1 Tf
-35.5972 -1.2983 Td
[()-8(\n)20()16()18()4()12()12()9()2(\n)20()]TJ
/F7 1 Tf
(\),)Tj
5.108 0 Td
(display)Tj
3.0274 0 Td
(dramatic)Tj
3.7984 0 Td
(variation)Tj
3.7984 0 Td
(in)Tj
1.0375 0 Td
(alkaloid)Tj
3.3788 0 Td
(toxicity)Tj
3.2032 0 Td
(throughout)Tj
4.7791 0 Td
(their)Tj
2.1033 0 Td
(ranges)Tj
2.8233 0 Td
([)Tj
0.83 0.64 0.02 0 k
(26)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(45)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(47)Tj
0 g
(].)Tj
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(In)Tj
1.1055 0 Td
(both)Tj
2.0636 0 Td
(species,)Tj
3.2202 0 Td
(variation)Tj
3.804 0 Td
(in)Tj
1.0318 0 Td
(both)Tj
2.0636 0 Td
(total)Tj
2.0013 0 Td
(toxicity)Tj
3.2031 0 Td
(and)Tj
1.7291 0 Td
(alkaloid)Tj
3.3789 0 Td
(profiles)Tj
3.2031 0 Td
(are)Tj
1.4457 0 Td
(strongly)Tj
3.4753 0 Td
(correlated)Tj
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(with)Tj
1.9956 0 Td
(a)Tj
0.6519 0 Td
(suite)Tj
2.0977 0 Td
(of)Tj
1.0148 0 Td
(associated)Tj
4.2576 0 Td
(phenotypes,)Tj
5.0286 0 Td
(such)Tj
2.0579 0 Td
(as)Tj
1.0148 0 Td
(aposematic)Tj
4.7055 0 Td
(coloration)Tj
4.3313 0 Td
([)Tj
0.83 0.64 0.02 0 k
(46)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(47)Tj
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3.2485 0 Td
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(multi-)Tj
-34.8092 -1.2982 Td
(trait)Tj
1.8879 0 Td
(selection)Tj
3.719 0 Td
(driven)Tj
2.8119 0 Td
(by)Tj
1.1849 0 Td
(toxicity)Tj
3.1975 0 Td
(as)Tj
1.0148 0 Td
(a)Tj
0.6576 0 Td
(predation)Tj
4.1102 0 Td
(defense.)Tj
/F13 1 Tf
3.4413 0 Td
[()-6()2()6()12(\n)20()13()4()22()11()8( )]TJ
5.142 0 Td
[()16()12(\n)20()22()7()-4( )]TJ
/F7 1 Tf
3.2371 0 Td
(is)Tj
0.8447 0 Td
(a)Tj
0.6577 0 Td
(member)Tj
3.5828 0 Td
(of)Tj
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(the)Tj
/F13 1 Tf
1.4683 0 Td
[()7()12()6()-4()11()11(\n)-9()12()-4( )]TJ
/F7 1 Tf
3.9345 0 Td
(group)Tj
2.6079 0 Td
(and)Tj
1.7291 0 Td
(was)Tj
1.7008 0 Td
(intentionally)Tj
5.3064 0 Td
(introduced)Tj
4.6431 0 Td
(to)Tj
1.0261 0 Td
(Manoa,)Tj
3.2599 0 Td
(Hawaii)Tj
3.0727 0 Td
(from)Tj
2.2053 0 Td
(Isla)Tj
1.6044 0 Td
(de)Tj
1.1679 0 Td
(Taboga,)Tj
-33.7264 -1.2982 Td
(Panama)Tj
3.4469 0 Td
(in)Tj
1.0375 0 Td
(1932)Tj
2.1203 0 Td
([)Tj
0.83 0.64 0.02 0 k
(48)Tj
0 g
(].)Tj
2.0806 0 Td
(The)Tj
1.7801 0 Td
(Manoa)Tj
3.0331 0 Td
(population)Tj
4.5921 0 Td
(displays)Tj
3.3902 0 Td
(substantially)Tj
5.2044 0 Td
(reduced)Tj
3.4469 0 Td
(alkaloid)Tj
3.3789 0 Td
(profiles)Tj
-33.511 -1.2983 Td
(relative)Tj
3.1351 0 Td
(to)Tj
1.0261 0 Td
(populations)Tj
4.955 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(native)Tj
2.6418 0 Td
(range)Tj
2.4662 0 Td
([)Tj
0.83 0.64 0.02 0 k
(25)Tj
0 g
(],)Tj
2.0749 0 Td
(allowing)Tj
3.617 0 Td
(us)Tj
1.1112 0 Td
(to)Tj
1.0261 0 Td
(test)Tj
1.5987 0 Td
(whether)Tj
3.4753 0 Td
(selection)Tj
3.719 0 Td
(against)Tj
-33.3522 -1.3039 Td
(costly)Tj
2.5115 0 Td
(alkaloid)Tj
3.3789 0 Td
(resistance)Tj
4.1272 0 Td
(due)Tj
1.7008 0 Td
(to)Tj
1.0261 0 Td
(reduction)Tj
4.1159 0 Td
(of)Tj
1.0148 0 Td
(dietary)Tj
2.9933 0 Td
(alkaloids)Tj
3.7417 0 Td
(is)Tj
0.8448 0 Td
(associated)Tj
4.2576 0 Td
(with)Tj
2.0012 0 Td
(a)Tj
0.652 0 Td
(loss)Tj
1.6951 0 Td
(of)Tj
1.0148 0 Td
(resis-)Tj
-35.0757 -1.2983 Td
(tance)Tj
2.3471 0 Td
(alleles.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 352.0062 cm
BT
/F3 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Materials)Tj
4.5071 0 Td
(and)Tj
1.989 0 Td
(methods)Tj
/F14 1 Tf
-6.4961 -1.5023 Td
(Sample)Tj
3.2787 0 Td
(collection)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 317.0267 cm
BT
/F7 1 Tf
1 TL
0.005 Tc
0 0 Td
(We)Tj
1.627 0 Td
(assembled)Tj
4.405 0 Td
(a)Tj
0.6633 0 Td
(collection)Tj
4.201 0 Td
(of)Tj
1.0318 0 Td
(whole)Tj
2.6532 0 Td
(livers)Tj
2.3981 0 Td
(from)Tj
2.2393 0 Td
(35)Tj
/F13 1 Tf
1.1906 0 Td
[()]TJ
/F7 1 Tf
(.)Tj
/F13 1 Tf
1.1565 0 Td
[()11()12()18()4()12()4()]TJ
/F7 1 Tf
3.2995 0 Td
(individuals)Tj
4.7508 0 Td
(collected)Tj
3.8155 0 Td
(in)Tj
1.0544 0 Td
(2006)Tj
-34.486 -1.3039 Td
(2007)Tj
2.1599 0 Td
([)Tj
0.83 0.64 0.02 0 k
(49)Tj
0 g
(],)Tj
2.1203 0 Td
(11)Tj
/F13 1 Tf
1.1906 0 Td
[()]TJ
/F7 1 Tf
(.)Tj
/F13 1 Tf
1.1565 0 Td
[()-8(\n)20()16()18()4()12()12()9()2(\n)-9()-4( )]TJ
/F7 1 Tf
5.023 0 Td
(collected)Tj
3.821 0 Td
(in)Tj
1.0545 0 Td
(2008)Tj
2.1543 0 Td
([)Tj
0.83 0.64 0.02 0 k
(46)Tj
0 g
(],)Tj
2.126 0 Td
(and)Tj
1.7575 0 Td
(15)Tj
/F13 1 Tf
1.1849 0 Td
[()]TJ
/F7 1 Tf
(.)Tj
/F13 1 Tf
1.1622 0 Td
[()16()12(\n)20()22()7()-4( )]TJ
/F7 1 Tf
3.2995 0 Td
(collected)Tj
3.8154 0 Td
(in)Tj
1.0545 0 Td
(2007)Tj
2.1599 0 Td
(and)Tj
-35.24 -1.2982 Td
(2015.)Tj
2.3924 0 Td
(The)Tj
/F13 1 Tf
1.8085 0 Td
[()]TJ
/F7 1 Tf
(.)Tj
/F13 1 Tf
1.1565 0 Td
[()11()12()18()4()12()4()]TJ
/F7 1 Tf
3.2995 0 Td
(samples)Tj
3.4469 0 Td
(represent)Tj
4.0365 0 Td
(six)Tj
1.3436 0 Td
(localities:)Tj
4.0195 0 Td
(Isla)Tj
1.6328 0 Td
(Bastimentos,)Tj
5.4538 0 Td
(Panama)Tj
3.5036 0 Td
(\(N)Tj
1.3153 0 Td
(=)Tj
0.805 0 Td
(9\);)Tj
1.2926 0 Td
(Isla)Tj
-35.5065 -1.2983 Td
(Pastores,)Tj
3.838 0 Td
(Panama)Tj
3.5036 0 Td
(\(N)Tj
1.3153 0 Td
(=)Tj
0.8107 0 Td
(4\);)Tj
1.2869 0 Td
(Isla)Tj
1.6384 0 Td
(Colo)Tj
0 Tc
1.5024 0.051 Td
()Tj
0.005 Tc
0.4535 -0.051 Td
(n,)Tj
1.0148 0 Td
(Panama)Tj
3.5036 0 Td
(\(N)Tj
1.3153 0 Td
(=)Tj
0.805 0 Td
(7\);)Tj
1.287 0 Td
(Tortuguero,)Tj
5.159 0 Td
(Costa)Tj
2.5285 0 Td
(Rica)Tj
2.0012 0 Td
(\(N)Tj
1.3153 0 Td
(=)Tj
0.805 0 Td
(8\);)Tj
-34.0835 -1.3039 Td
(Puerto)Tj
2.9593 0 Td
(Viejo,)Tj
2.6475 0 Td
(Costa)Tj
2.5285 0 Td
(Rica)Tj
2.0013 0 Td
(\(N)Tj
1.3152 0 Td
(=)Tj
0.8107 0 Td
(5\);)Tj
1.287 0 Td
(and)Tj
1.7574 0 Td
(Guapiles,)Tj
4.0195 0 Td
(Costa)Tj
2.5285 0 Td
(Rica)Tj
2.0013 0 Td
(\(N)Tj
1.3152 0 Td
(=)Tj
0.8051 0 Td
(2\).)Tj
1.2926 0 Td
(Toxicity)Tj
3.5829 0 Td
(in)Tj
/F13 1 Tf
1.0545 0 Td
[()-6()2()6()12(\n)20()13()4()22()11()8( )]TJ
/F7 1 Tf
-31.9065 -1.2983 Td
(has)Tj
1.5703 0 Td
(been)Tj
2.1544 0 Td
(quantified)Tj
4.3993 0 Td
(through)Tj
3.5093 0 Td
(several)Tj
2.999 0 Td
(methods,)Tj
3.9798 0 Td
(most)Tj
2.245 0 Td
(notably)Tj
3.2769 0 Td
(mouse)Tj
2.9026 0 Td
(sensitivity)Tj
4.32 0 Td
(assays)Tj
2.6816 0 Td
(in)Tj
1.0544 0 Td
(which)Tj
-35.0926 -1.2982 Td
(alkaloid)Tj
3.4469 0 Td
(extracts)Tj
3.3675 0 Td
(are)Tj
1.4797 0 Td
(injected)Tj
3.4582 0 Td
(subcutaneously)Tj
6.4913 0 Td
(into)Tj
1.8822 0 Td
(lab)Tj
1.4287 0 Td
(mice)Tj
2.194 0 Td
(\(similar)Tj
3.3958 0 Td
(in)Tj
1.0545 0 Td
(principle)Tj
3.8835 0 Td
(to)Tj
1.0431 0 Td
(commonly)Tj
-33.1254 -1.304 Td
(used)Tj
2.0919 0 Td
(LD)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 233.8582 224.3338 cm
BT
/F7 1 Tf
1 TL
0.0067 Tc
0 0 Td
(50)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 243.3826 225.9779 cm
BT
/F7 1 Tf
1 TL
0.005 Tc
0 0 Td
(assays\))Tj
3.0273 0 Td
([)Tj
0.83 0.64 0.02 0 k
(46)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(47)Tj
0 g
(])Tj
3.0898 0 Td
(and)Tj
1.7574 0 Td
(gas)Tj
1.5081 0 Td
(chromatography)Tj
7.0072 0 Td
(with)Tj
2.0296 0 Td
(mass)Tj
2.2336 0 Td
(spectrometry)Tj
5.5956 0 Td
(\(GC-MS\))Tj
4.0592 0 Td
(to)Tj
-34.6447 -1.2982 Td
(characterize)Tj
5.1362 0 Td
(alkaloid)Tj
3.4526 0 Td
(profiles)Tj
3.2712 0 Td
([)Tj
0.83 0.64 0.02 0 k
(26)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(50)Tj
0 g
(].)Tj
3.3278 0 Td
(Subcutaneous)Tj
5.8904 0 Td
(mouse)Tj
2.9026 0 Td
(assays)Tj
2.6759 0 Td
(have)Tj
2.0976 0 Td
(been)Tj
2.16 0 Td
(criticized)Tj
-30.9143 -1.2983 Td
(because)Tj
3.3788 0 Td
(mice)Tj
2.1939 0 Td
(are)Tj
1.4741 0 Td
(not)Tj
1.5987 0 Td
(clearly)Tj
2.8856 0 Td
(analogous)Tj
4.3313 0 Td
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1.0432 0 Td
(the)Tj
1.4967 0 Td
(natural)Tj
3.1407 0 Td
(predators)Tj
4.1159 0 Td
(of)Tj
1.0318 0 Td
(these)Tj
2.2961 0 Td
(species)Tj
3.0614 0 Td
(and)Tj
1.7574 0 Td
(because)Tj
-33.8056 -1.3039 Td
(predators)Tj
4.1102 0 Td
(receive)Tj
3.0726 0 Td
(toxins)Tj
2.7213 0 Td
(orally)Tj
2.5284 0 Td
(rather)Tj
2.7043 0 Td
(than)Tj
2.0636 0 Td
(subcutaneously)Tj
6.4913 0 Td
(in)Tj
1.0545 0 Td
(nature)Tj
2.88 0 Td
([)Tj
0.83 0.64 0.02 0 k
(51)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(52)Tj
0 g
(].)Tj
3.3221 0 Td
(These)Tj
2.6136 0 Td
(assays)Tj
-33.5619 -1.2983 Td
(also)Tj
1.8028 0 Td
(include)Tj
3.2484 0 Td
(the)Tj
1.4967 0 Td
(effects)Tj
2.7892 0 Td
(of)Tj
1.0318 0 Td
(alkaloids)Tj
3.8211 0 Td
(that)Tj
1.8142 0 Td
(do)Tj
1.2699 0 Td
(not)Tj
1.6044 0 Td
(interact)Tj
3.3562 0 Td
(with)Tj
2.0296 0 Td
(Na)Tj
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Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 454.5637 172.3464 cm
BT
/F7 1 Tf
1 TL
0.0067 Tc
0 0 Td
(V)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 459.8362 173.9905 cm
BT
/F7 1 Tf
1 TL
0.005 Tc
0 0 Td
(1.4)Tj
1.4229 0 Td
(channels.)Tj
4.0422 0 Td
(However,)Tj
4.1499 0 Td
(esti-)Tj
-35.5971 -1.2982 Td
(mates)Tj
2.6021 0 Td
(from)Tj
2.2394 0 Td
(mouse)Tj
2.9027 0 Td
(assays)Tj
2.6815 0 Td
(generally)Tj
3.9118 0 Td
(correlate)Tj
3.7984 0 Td
(with)Tj
2.0353 0 Td
(the)Tj
1.4966 0 Td
(diversity)Tj
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(and)Tj
1.7574 0 Td
(concentration)Tj
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(of)Tj
1.0375 0 Td
(major)Tj
-34.1231 -1.2983 Td
(alkaloids)Tj
3.821 0 Td
(in)Tj
1.0545 0 Td
(these)Tj
2.2961 0 Td
(species)Tj
3.0614 0 Td
([)Tj
0.83 0.64 0.02 0 k
(26)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
(45)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(47)Tj
0 g
(].)Tj
4.8188 0 Td
(Additionally,)Tj
5.5729 0 Td
(although)Tj
3.8268 0 Td
(not)Tj
1.5986 0 Td
(representative)Tj
5.964 0 Td
(for)Tj
1.4117 0 Td
(the)Tj
1.4967 0 Td
(route)Tj
-34.9225 -1.3039 Td
(of)Tj
1.0318 0 Td
(introduction)Tj
5.4198 0 Td
(in)Tj
1.0544 0 Td
(predators,)Tj
4.3484 0 Td
(for)Tj
/F13 1 Tf
1.4116 0 Td
[()-6()2()6()12(\n)20()13()4()22()11()8( )]TJ
/F7 1 Tf
5.2384 0 Td
(themselves)Tj
4.6488 0 Td
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