Biology subjects

Bates, J.

Publications and source records attributed to Bates, J..

7 recordsLinked to original sources

bioRxiv2026

BoltzProt-1: Towards Efficient De Novo Binder Design with Good Developability

Designing binders against novel protein targets remains a central challenge in computational drug discovery. Here we introduce BoltzProt-1, a pipeline for generating protein binders, including nanobodies, with improved hit rates and favorable developability properties. At its core lie a refined iteration of BoltzGens generative model and a novel protein-protein interaction prediction model, BoltzPPI. Employing BoltzPPI instead of BoltzGens standard structure-prediction confidence metrics to rank nanobody (VHH) designs increases the confirmed-binder hit rate from 3.3% to 8.0% across 10 novel targets. Assessed on 10 additional targets used in prior literature, the BoltzProt-1 pipeline obtains nanobody screening hits for 7 of 10 targets, surpassing the 6 of 10 previously reported by Chai-2. Finally, evaluating the developability of BoltzProt-1-designed nanobodies in terms of stability, aggregation, purity, polyspecificity and hydrophobicity reveals that 58% of its confirmed binders pass every criterion, exceeding both BoltzGen (40%) and clinical-stage VHH controls (21%). O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/733997v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@d86de1org.highwire.dtl.DTLVardef@115da7eorg.highwire.dtl.DTLVardef@1bbb4e9org.highwire.dtl.DTLVardef@626a68_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2026

Foraging behavior, not prey identity, facilitates niche packing in a tropical montane avifauna

Understanding the mechanisms of key ecological and evolutionary patterns and the restructuring of biodiversity in the Anthropocene is contingent on filling knowledge gaps about resource consumption across trophic levels and how resource use is limited by factors intrinsic to organisms and extrinsic aspects of the environment across deep and shallow timespans. We quantified diet composition and foraging behavior across a community of invertivorous birds in the Ecuadorian Andes to explore how resource use facilitates the packing and expansion of niche space across an elevational gradient, contributing the tropical Andes status as the most species-rich region on earth. We found evidence that niche packing of morphologically similar species may be offset by greater behavioral plasticity in foraging behavior at species-rich lower elevations where competition is likely more intense and invertebrate prey more diverse. We also tested the extent to which the breadth and similarity of birds foraging and dietary niches are shaped by the environmental and competitive gradient across elevation versus species identity and phylogenetic similarity. The specific behaviors and substrates that birds used were far more strongly associated with species identity than elevation, particularly for behaviors requiring specialized morphology that is phylogenetically conserved. In contrast, species identity had little effect on prey selection, which was more strongly associated with elevation. Our findings suggest that elevational range dynamics and niche packing of tropical montane birds are more strongly shaped by phylogenetic constraints on foraging behavior than by specializing on specific prey taxa, highlighting the importance of maintaining structural integrity in tropical forests for preserving functional diversity.

ecology↗

bioRxiv2026

Range-wide phylogeography, population genomics, and demography of three widespread Ara macaws (Psittacidae)

Macaws of the genus Ara comprise eight extant species distributed throughout the Neotropics. Among them, four have broad geographic ranges, yet little is known about the evolutionary history and demographic processes that shaped their genomic variation and present-day distributions. This is particularly relevant because, although these wide-ranging macaws are classified as Least Concern by the IUCN, many of their populations are declining due to habitat fragmentation, illegal trade, and climate change. Here, we used nuclear and mitochondrial genomic data to characterize the evolutionary relationships, population structure, genetic diversity, and demographic histories of three widely distributed species (A. ararauna, A. chloropterus, and A. severus) across their geographic distributions. We identified two main populations within Ara severus, and this species showed the highest heterozygosity levels among the three species. In A. ararauna and A. chloropterus, we observed four main genetic clusters corresponding to two populations in the Amazon rainforest biome and and two populations in the Cerrado savanna biome. Cerrado populations in both species exhibited markedly reduced heterozygosity and elevated inbreeding relative to Amazonian populations, consistent with smaller effective population sizes and increased isolation. Genome-wide scans suggested that genetic drift and divergent demographic histories played a predominant role in driving the strong differentiation between Amazon and Cerrado in these two species. Nevertheless, we detected two candidate genes, NALCN and RBBP6, with convergent selection signals across A. ararauna and A. chloropterus, suggesting possible local adaptation to the Cerrado biome.

evolutionary biology↗

bioRxiv2026

Phylogenomics and biogeography of the parrot genus Pyrrhura with implications for systematics and conservation

The genus Pyrrhura (Psittacidae: Arini) is one of the most diverse groups of Neotropical parrots. Its species are charismatic, widely kept as pets, and frequently bred outside their native ranges. Yet, nearly half are currently listed as threatened by the IUCN within their natural distributions. Conservation assessments and population estimates often depend on the validity of accepted taxonomic boundaries. However, despite previous systematic efforts, the evolutionary relationships among and within many Pyrrhura species remain poorly resolved, largely due to a recent and rapid radiation. Here, we generated whole-genome sequences for all currently recognized Pyrrhura species, including multiple intraspecific taxa, to reconstruct a robust nuclear phylogeny under the multi-species coalescent model, alongside the most comprehensive mitogenome-based phylogeny of the genus to date. Although both phylogenies supported the monophyly of most currently accepted species, we identified several instances of mito-nuclear discordance, particularly involving the placement of early-diverging lineages, which are best explained by incomplete lineage sorting and historical gene flow. Additionally, we detected three distinct captive lineages that do not cluster with any known wild populations, suggesting substantial overlooked genetic diversity in the worlds captive populations. Ancestral range reconstructions indicate multiple and relatively recent colonization events into the northern and central Andes, likely associated with the uplift of the Andes and the emergence of new ecological niches. Together, our results reveal a complex evolutionary history in Pyrrhura, shaped by rapid radiations, incomplete lineage sorting, and gene flow. We show that integrating nuclear and mitochondrial data with broad geographic and taxonomic sampling, including captive individuals, can uncover overlooked genetic diversity and help to resolve long-standing systematic uncertainties. Finally, we show that several topological discrepancies among previous studies can be attributed to differences in sampling strategies, particularly within the most polytypic Pyrrhura species.

evolutionary biology↗

bioRxiv2024

2500 Years of Human Betaherpesvirus 6A and 6B Evolution Revealed by Ancient DNA

Human betaherpesviruses 6A and 6B are double-stranded DNA viruses, specialised in infecting humans and are best known as the main causative pathogens of the common childhood infection "sixth disease". Despite only being discovered in the 1980s, these viruses are speculated to have a much longer and more complex history within the human population than available modern data make clear. The viruses are carried by large fractions of the human population and can integrate into the human genome, leading to a wide range of clinical manifestations of varied severity. Here, we present the first nine full and two partial ancient genomes of HHV-6A and 6B, dating as far back as the Italian Iron Age (ca. 1100-600 BCE). We demonstrate that large fractions of the current HHV-6 diversity were already well established in the human population by the 14th century CE. Our data suggests that HHV-6B integrated into the human genome at the latest before the 1st-6th century CE, with two integrated clades being populated by ancient DNA genomes in our phylogeny, which further supports that they originated from likely much older ancient founder events. Additionally, we show that all known inherited chromosomally integrated (ici-)HHV-6A clades were already represented in European historical populations, confirming that ici-HHV-6A no longer integrates into the human germline within populations of European ancestry and likely endogenized in early human history. Finally, our results demonstrate the unique suitability of archaeological remains and ancient DNA for the study of the evolution of integrated viruses in human populations.

evolutionary biology↗

bioRxiv2020

Landscape configuration of an Amazonian island-like ecosystem drives population structure and genetic diversity of a habitat-specialist bird

ContextAmazonian white-sand ecosystems (campinas) are open vegetation patches which form a natural island-like system in a matrix of tropical rainforest. Due to their clear distinction from the surrounding matrix, the spatial characteristics of campina patches may affect the genetic diversity and composition of their specialized organisms such as the small and endemic passerine Elaenia ruficeps. ObjectivesHere, we estimate the relative contribution of the current extension, configuration and geographical context of campina patches to the patterns of genetic diversity and population structure of E. ruficeps. MethodsWe sampled individuals of E. ruficeps from three landscapes in Central Amazonia with contrasting campina spatial distribution, from landscapes with large and connected patches to landscapes with small and isolated patches. We estimate population structure, genetic diversity, and contemporary and historical migration within and among the three landscapes and used landscape metrics as predictor variables. Furthermore, we estimate genetic isolation by distance and resistance among individuals sampled within landscapes. ResultsWe identified three genetically distinct populations with asymmetrical gene flow among landscapes and a decreasing migration rate with distance. Within each landscape, we found low genetic differentiation without genetic isolation by distance nor by resistance. In contrast, we found differentiation and spatial correlation between landscapes. ConclusionsOur results uncover population dynamics of E. ruficeps through time. Together with previous studies, this suggests that both regional context and landscape structure shape the connectivity among populations of campina specialist birds, and that Amazonian landscapes, together with their associated biota, have responded to recent climatic changes.

ecology↗

bioRxiv2019

Trivalent cocktail of de novo designed immunogens enables the robust induction and focusing of functional antibodies in vivo

De novo protein design has been successful in expanding the natural protein repertoire. However, most de novo proteins lack biological function, presenting a major methodological challenge. In vaccinology, the induction of precise antibody responses remains a cornerstone for next-generation vaccines. Here, we present a novel protein design algorithm, termed TopoBuilder, with which we engineered epitope-focused immunogens displaying complex structural motifs. Both in mice and non-human primates, cocktails of three de novo designed immunogens induced robust neutralizing responses against the respiratory syncytial virus. Furthermore, the immunogens refocused pre-existing antibody responses towards defined neutralization epitopes. Overall, our de novo design approach opens the possibility of targeting specific epitopes for vaccine and therapeutic antibody development, and more generally will be applicable to design de novo proteins displaying complex functional motifs.

bioengineering↗