Biology subjects

Beltran, J. F.

Publications and source records attributed to Beltran, J. F..

3 recordsLinked to original sources

bioRxiv2024

Genomic, phenotypic and environmental correlates of speciation in the midwife toads (Alytes)

Speciation, i.e., the formation of new species, implies that diverging populations evolve genetic and phenotypic factors that promote reproductive isolation (RI), but the adaptive vs. neutral origin of these factors and their relative contributions across the speciation continuum remain elusive. Here we test which of genomic, bioacoustic, morphological and environmental differentiation best predicts RI across the midwife toads (genus Alytes), a diversification of Mediterranean amphibians. Hybrid zone analyses in the A. obstetricans complex support that without strong geographic barriers to dispersal, the extent of introgression (which should reflect the strength of RI) covaries with genomic divergence irrespective of other factors. Phenotypic divergence become important later along the continuum, namely between non-admixing species attributed to distinct subgenera. Our results suggest that by putatively causing intrinsic incompatibilities in hybrids, the genetic mutations accumulating randomly between allopatric populations act as the initial trigger of RI, while substantial ecological and behavioral differentiation is a long-term consequence of species divergence that ultimately promotes sympatry. Whereas speciation is usually claimed to be primarily adaptive, our study corroborates recent findings that new species may also be a neutral outcome of gradual phylogeographic divergence, which has practical implications for species delimitation.

evolutionary biology↗

bioRxiv2019

Host-microbiome protein-protein interactions capture mechanisms in human disease

Host-microbe interactions are crucial for normal physiological and immune system development and are implicated in a wide variety of diseases, including inflammatory bowel disease (IBD), colorectal cancer (CRC), obesity, and type 2 diabetes (T2D). Despite large-scale case-control studies aimed at identifying microbial taxa or specific genes involved in pathogeneses, the mechanisms linking them to disease have thus far remained elusive. To identify potential mechanisms through which human-associated bacteria impact host health, we leveraged publicly-available interspecies protein-protein interaction (PPI) data to find clusters of microbiome-derived proteins with high sequence identity to known human protein interactors. We observe differential targeting of putative human-interacting bacterial genes in metagenomic case-control microbiome studies. In nine independent case studies, we find evidence that the microbiome broadly targets human proteins involved in immune, oncogenic, apoptotic, and endocrine signaling pathways in relation to IBD, CRC, obesity and T2D diagnoses. This host-centric analysis strategy provides a mechanistic hypothesis-generating platform for any metagenomics cohort study and extensively adds human functional annotation to commensal bacterial proteins. One-sentence summaryMicrobiome-derived proteins are linked to disease-associated human pathways by metagenomic and protein-protein interaction analyses.

microbiology↗

bioRxiv2017

Interactome INSIDER: A Multi-Scale Structural Interactome Browser For Genomic Studies

Protein interactions underlie nearly all known cellular function, making knowledge of their binding conformations paramount to understanding the physical workings of the cell. Studying binding conformations has allowed scientists to explore some of the mechanistic underpinnings of disease caused by disruption of protein interactions. However, since experimentally determined interaction structures are only available for a small fraction of the known interactome such inquiry has largely excluded functional genomic studies of the human interactome and broad observations of the inner workings of disease. Here we present Interactome INSIDER, an information center for genomic studies using the first full-interactome map of human interaction interfaces. We applied a new, unified framework to predict protein interaction interfaces for 184,605 protein interactions with previously unresolved interfaces in human and 7 model organisms, including the entire experimentally determined human binary interactome. We find that predicted interfaces share several known functional properties of interfaces, including an enrichment for disease mutations and recurrent cancer mutations, suggesting their applicability to functional genomic studies. We also performed 2,164 de novo mutagenesis experiments and show that mutations of predicted interface residues disrupt interactions at a similar rate to known interface residues and at a much higher rate than mutations outside of predicted interfaces. To spur functional genomic studies in the human interactome, Interactome INSIDER (http://interactomeinsider.yulab.org) allows users to explore known population variants, disease mutations, and somatic cancer mutations, or upload their own set of mutations to find enrichment at the level of protein domains, residues, and 3D atomic clustering in known and predicted interaction interfaces.

genomics↗