Domesticated animals that revert to a wild state can become invasive and significantly impact native biodiversity. Although dogs can be problematic locally, only the Australasian dingo is known to ...occur in isolation from humans. Western dogs have experienced more intense artificial selection, which potentially limits their invasiveness. However, feral dogs eradicated from Isabela Island, Galápagos in the 1980s could be the first‐known exception. We used DNA and morphometric data from 92 of these dogs to test the hypotheses that (i) these dogs persisted independently of humans for up to a century and a half since descending from a handful of dogs introduced in the early 1800s, vs. (ii) similarly to other western feral dog populations, they reflected continuous recruitment of strays from human settlements on a portion of the Island. We detected one dominant maternal lineage and one dominant paternal lineage shared by the three subpopulations, along with low autosomal genetic diversity, consistent with the hypothesized common origins from a small founder population. Genetic diversity patterns among the three island subpopulations were consistent with stepping‐stone founder effects, while morphometric differentiation suggested rapid phenotypic divergence, possibly due to drift and reinforced by selection corresponding to distinct microclimates and habitats on Isabela. Despite the continued presence of free‐ranging dogs in the vicinity of settlements on Isabela and other Galápagos Islands, feral populations have not reestablished in remote areas since the 1980s, emphasizing the rarity of conditions necessary for feralization of modern western dogs.
The Plasmodium falciparum Pfs25 protein (Pfs25) is a leading malaria transmission-blocking vaccine antigen. Pfs25 vaccination is intended to elicit antibodies that inhibit parasite development when ...ingested by Anopheles mosquitoes during blood meals. The Pfs25 three-dimensional structure has remained elusive, hampering a molecular understanding of its function and limiting immunogen design. We report six crystal structures of Pfs25 in complex with antibodies elicited by immunization via Pfs25 virus-like particles in human immunoglobulin loci transgenic mice. Our structural findings reveal the fine specificities associated with two distinct immunogenic sites on Pfs25. Importantly, one of these sites broadly overlaps with the epitope of the well-known 4B7 mouse antibody, which can be targeted simultaneously by antibodies that target a non-overlapping site to additively increase parasite inhibition. Our molecular characterization of inhibitory antibodies informs on the natural disposition of Pfs25 on the surface of ookinetes and provides the structural blueprints to design next-generation immunogens.
Lasting protection has long been a goal for malaria vaccines. The major surface antigen on Plasmodium falciparum sporozoites, the circumsporozoite protein (PfCSP), has been an attractive target for ...vaccine development and most protective antibodies studied to date interact with the central NANP repeat region of PfCSP. However, it remains unclear what structural and functional characteristics correlate with better protection by one antibody over another. Binding to the junctional region between the N-terminal domain and central NANP repeats has been proposed to result in superior protection: this region initiates with the only NPDP sequence followed immediately by NANP. Here, we isolated antibodies in Kymab mice immunized with full-length recombinant PfCSP and two protective antibodies were selected for further study with reactivity against the junctional region. X-ray and EM structures of two monoclonal antibodies, mAb667 and mAb668, shed light on their differential affinity and specificity for the junctional region. Importantly, these antibodies also bind to the NANP repeat region with equal or better affinity. A comparison with an NANP-only binding antibody (mAb317) revealed roughly similar but statistically distinct levels of protection against sporozoite challenge in mouse liver burden models, suggesting that junctional antibody protection might relate to the ability to also cross-react with the NANP repeat region. Our findings indicate that additional efforts are necessary to isolate a true junctional antibody with no or much reduced affinity to the NANP region to elucidate the role of the junctional epitope in protection.
Abstract
Domesticated animals that revert to a wild state can become invasive and significantly impact native biodiversity. Although dogs can be problematic locally, only the
A
ustralasian dingo is ...known to occur in isolation from humans. Western dogs have experienced more intense artificial selection, which potentially limits their invasiveness. However, feral dogs eradicated from
I
sabela
I
sland,
G
alápagos in the 1980s could be the first‐known exception. We used
DNA
and morphometric data from 92 of these dogs to test the hypotheses that (i) these dogs persisted independently of humans for up to a century and a half since descending from a handful of dogs introduced in the early 1800s, vs. (ii) similarly to other western feral dog populations, they reflected continuous recruitment of strays from human settlements on a portion of the Island. We detected one dominant maternal lineage and one dominant paternal lineage shared by the three subpopulations, along with low autosomal genetic diversity, consistent with the hypothesized common origins from a small founder population. Genetic diversity patterns among the three island subpopulations were consistent with stepping‐stone founder effects, while morphometric differentiation suggested rapid phenotypic divergence, possibly due to drift and reinforced by selection corresponding to distinct microclimates and habitats on
I
sabela. Despite the continued presence of free‐ranging dogs in the vicinity of settlements on
I
sabela and other
G
alápagos
I
slands, feral populations have not reestablished in remote areas since the 1980s, emphasizing the rarity of conditions necessary for feralization of modern western dogs.
As part of an effort to control introduced species in the Galápagos, feral dogs were eradicated in the 1980s from Isabela Island, where the dogs had occurred independently of humans for at least 100 ...years. Although their initial introduction was likely by European explorers, translocation by indigenous people from the South American mainland was also a possibility. At the time of eradication, Barnett (1985) described three morphologically distinct and ecologically specialized dog populations that occupied distinct portions of the island. Whether these populations had become genetically isolated or remained differentiated in the face of gene flow is unknown. We extracted DNA from 92 of the eradicated dogs. Due to poor quality DNA, we were able to obtain results for 30–54 individuals, depending on the genetic marker. We used mitochondrial, Y chromosome, and microsatellite markers to determine their origins and to investigate gene flow among the three populations. Both the mitochondrial and Y chromosome haplotypes were consistent with European ancestry. Microsatellite analysis suggested that the two most remote of the three populations were genetically very similar, suggesting high gene flow or insufficient time for genetic differentiation despite their morphological and ecological differences. The population closest to permanent human settlements also shared many alleles, but exhibited higher genetic diversity, potentially owing to more recent domestic introductions to feral populations.
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