mortality. In stark contrast, 95% of workers treated
with S. invicta venom solution followed by formic
acid solution survived (Wilcoxon: c2 = 25.4, df =
1, P < 0.0001) (Fig. 3C). Thus, formic acid appears to be the compound responsible for detoxifying S. invicta venom.
How formic acid renders fire ant venom nontoxic is unresolved. Five principal piperidine alkaloids (2,6-dialkylpiperidines) and some of their
stereoisomers primarily make up S. invicta venom
(10). Suspended in this are small amounts of
proteins (approximately 1% of the total), primarily the enzymes phospholipase A and hyaluronidase (17). The insecticidal properties of S. invicta
venom derive directly from its alkaloids (13). However, associated enzymes function as cell membrane disruptors (18) and may be critical for gating
alkaloids through intercuticular membranes and
cell walls. Formic acid denatures these enzymes.
This indirect effect seems the most likely detoxification mechanism. It is unknown whether formic
acid alters the bioactivity of the alkaloid fraction.
N. fulva and other formicines use formic acid
as a chemical weapon because it is highly caustic.
Self-applying formic acid is thus costly, favoring
selectivity in the expression of the detoxification
behavior. We evaluated the specificity of detoxification expression by measuring its intensity
after interactions with S. invicta versus after interactions with a series of seven test species that
employ defensive compounds in interspecific
conflicts. In vials, two-on-one interactions (test species versus N. fulva) were staged, ending when
test ants applied defensive compounds to N. fulva
(14). After chemical conflict with any test species,
N. fulva workers performed significantly more
detoxification behaviors than they did when there
was no conflict (Fig. 4 and table S1). However,
after chemical conflict with S. invicta, N. fulva
workers performed the detoxification behavior
with much higher frequency than after conflict
with any other species (Fig. 4 and table S2). In
fact, the median detoxification response after
conflict with S. invicta was performed 6.7 times
more frequently than the average response after
conflicts with non–fire ant species. Curiously,
detoxification behaviors were not unusually ele-
vated after exposure to S. richteri workers, a close-
ly related South American fire ant.
N. fulva and S. invicta share an evolutionarily ancient interaction. Although it is broadly
expressed after chemical conflicts, the intense
expression of detoxification behavior appears
specific to interactions with S. invicta. We suggest that the behavior of N. fulva of applying
toxic formic acid to its own cuticle may constitute an adaptation to competition with S. invicta
in South America. In some South American ant
assemblages, N. fulva is dominant to S. invicta
but subordinate to species below S. invicta in the
assemblage dominance hierarchy (8). This intransitive interaction, rare in ant assemblages, may
be a hallmark, from their ancestral range, of this
competitor-specific defensive adaptation.
The use of defensive compounds to achieve
competitive dominance is widespread and amazingly varied in ants (19, 20). Particularly potent
defensive chemistries can even protect native species from extirpation by dominant invaders (21).
However, achieving competitive dominance by self-applying a chemical as an antidote to a competitor’s venom is remarkable. The ability of N. fulva
to detoxify fire ant venom is probably a key factor contributing to the ecologically important
population-level displacement of imported fire
ants by N. fulva that is underway in areas of the
southern United States (11).
References and Notes
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14. Methods are described in the supplementary materials.
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16. B. D. Jackson, E. D. Morgan, Chemoecology 4, 125–144
17. M. S. Blum, J. Toxicol. Toxin Rev. 11, 115–164 (1992).
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19. A. N. Andersen, M. S. Blum, T. H. Jones, Oecologia 88,
20. A. Buschinger, U. Maschwitz, in Defensive Mechanisms in
Social Insects, H. R. Hermann, Ed. (Praeger, New York,
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Acknowledgments: We thank M. Marischen and P. Diebold for
technical assistance and N. Youssef and J. Oliver for providing
S. richteri. E. Sarnat provided a technical drawing, and
S. Stokes assisted in formulating the formic acid solution.
R. Plowes provided useful discussion. Funding was provided
by the Helen C. Kleberg and Robert J. Kleberg Foundation and
the Lee and Ramona Bass Foundation. Data are archived at
the Dryad Digital Repository, doi: 10.5061/dryad.5t110.
Materials and Methods
Tables S1 and S2
11 September 2013; accepted 22 January 2014
Resurrecting Surviving Neandertal
Lineages from Modern Human Genomes
Benjamin Vernot and Joshua M. Akey*
Anatomically modern humans overlapped and mated with Neandertals such that non-African humans
inherit ~1 to 3% of their genomes from Neandertal ancestors. We identified Neandertal lineages
that persist in the DNA of modern humans, in whole-genome sequences from 379 European and
286 East Asian individuals, recovering more than 15 gigabases of introgressed sequence that spans
~20% of the Neandertal genome (false discovery rate = 5%). Analyses of surviving archaic lineages
suggest that there were fitness costs to hybridization, admixture occurred both before and after
divergence of non-African modern humans, and Neandertals were a source of adaptive variation for loci
involved in skin phenotypes. Our results provide a new avenue for paleogenomics studies, allowing
substantial amounts of population-level DNA sequence information to be obtained from extinct groups,
even in the absence of fossilized remains.
Hybridization between closely related spe- cies, and the concomitant transfer or in- trogression of DNA, is widespread in
nature (1, 2). In hominin evolution, the sequenc-
ing of Neandertals (3) and their sister lineage,
Denisovans (4, 5), provided evidence for introgres-
sion of these lineages into modern humans. Spe-
cifically, ~1 to 3% of each non-African human
genome is estimated to have been inherited from
Neandertals (3, 5). Although initial inferences of
introgression between Neandertals and hu-
mans may not have been robust to alternative
explanations—most notably, archaic population
structure (3, 6)—subsequent analyses have pro-
vided evidence for gene flow (7–9).
We hypothesized that a substantial amount
of the Neandertal genome may be recovered from
the analysis of contemporary humans despite the
limited amounts of admixture, as introgressed sequences may vary among individuals (Fig. 1A).
Coalescent simulations for a broad range of admixture models suggest that 35 to 70% of the
Neandertal genome persists in the DNA of present-day humans (figs. S1 and S2) (10). By identifying
Neandertal sequences from a large sample of
modern humans, we hope to discover surviving
Department of Genome Sciences, University of Washington,
Seattle, WA 98195, USA.
*Corresponding author. E-mail: firstname.lastname@example.org