Biology subjects

Leonard, A. S.

Publications and source records attributed to Leonard, A. S..

24 records · Page 2Linked to original sources

bioRxiv2022

Graph construction method impacts variation representation and analyses in a bovine super-pangenome

Several models and algorithms have been proposed to build pangenomes from multiple input assemblies, but their impact on variant representation, and consequently downstream analyses, is largely unknown. We create multi-species "super-pangenomes" using pggb, cactus, and minigraph with the Bos taurus taurus reference sequence and eleven haplotype-resolved assemblies from taurine and indicine cattle, bison, yak, and gaur. We recover 221k nonredundant structural variations (SVs) from the pangenomes, of which 135k (61%) are common to all three. SVs derived from assembly-based calling show high agreement with the consensus calls from the pangenomes (96%), but validate only a small proportion of variations private to each graph. Pggb and cactus, which also incorporate base-level variation, have approximately 95% exact matches with assembly-derived small variant calls, which significantly improves the edit rate when realigning assemblies compared to minigraph. We use the three pangenomes to investigate 9,566 variable number tandem repeats (VNTRs), finding 63% have identical predicted repeat counts in the three graphs, while minigraph can over or underestimate the count given its approximate coordinate system. We examine a highly variable VNTR locus and show that repeat unit copy number impacts expression of proximal genes and non-coding RNA. Our findings indicate good consensus between the three pangenome methods but also show their individual strengths and weaknesses that need to be considered when analysing different types of variants from multiple input assemblies.

genomics↗

bioRxiv2022

Octopamine affects gustatory responsiveness and associative learning performance in bumble bees

Octopamine has broad roles within invertebrate nervous systems as a neurohormone, neurotransmitter and neuromodulator. It orchestrates foraging behavior in many insect taxa via effects on feeding, gustatory responsiveness and appetitive learning. Knowledge of how this biogenic amine regulates bee physiology and behavior is based largely on study of a single species, the honey bee, Apis mellifera. Until recently, its role in the foraging ecology and social organization of diverse bee taxa had been unexplored. Bumble bees (Bombus spp.) are a model for the study of foraging and learning, and its neural basis, but whether octopamine similarly affects sensory and cognitive performance in this genus is not known. To address this gap, we explored the effects of octopamine on sucrose response thresholds and associative learning in Bombus impatiens via conditioning of the Proboscis Extension Reflex (PER) using a visual (color) cue. We found that octopamine had similar effects on bumble bee behavior as honey bees, however, higher doses were required to induce these effects. At this higher dose, octopamine lowered bees sucrose response thresholds and appeared to enhance associative learning performance. Adding to recent studies on stingless bees (Meliponini), these findings support the idea that octopamines role in reward processing and learning is broadly conserved across Apidae, while pointing towards some differences across systems worth exploring further.

animal behavior and cognition↗

bioRxiv2021

Bovine pangenome reveals trait-associated structural variation from diverse assembly inputs

Advantages of pangenomes over linear reference assemblies for genome research have recently been established. However, potential effects of sequence platform and assembly approach, or of combining assemblies created by different approaches, on pangenome construction have not been investigated. We generated haplotype-resolved assemblies from the offspring of three bovine trios representing increasing levels of heterozygosity that each demonstrate a substantial improvement in contiguity, completeness, and accuracy over the current Bos taurus reference genome. Diploid coverage as low as 20x for HiFi or 60x for ONT was sufficient to produce two haplotype-resolved assemblies meeting the standards set by the Vertebrate Genome Project. Structural variant-based pangenomes created from the haplotype-resolved assemblies demonstrated significant consensus regardless of sequence platform, assembler algorithm, or coverage. Inspecting pangenome topologies identified 90 thousand structural variants including 931 overlapping with coding sequences; this approach revealed variants affecting QRICH2, PRDM9, HSPA1A, TAS2R46, and GC that have potential to affect phenotype.

genomics↗

bioRxiv2021

Novel functional sequences uncovered through a bovine multi-assembly graph

Linear reference genomes are typically assembled from single individuals. They are unable to reflect the genetic diversity of populations and lack millions of bases. To overcome such limitations and make non-reference sequences amenable to genetic investigations, we build a multi-assembly graph from six reference-quality assemblies from taurine cattle and their close relatives. We uncover 70,329,827 bases that are missing in the bovine linear reference genome. The missing sequences encode novel transcripts that are differentially expressed between individual animals. Reads which were previously poorly or unmapped against the bovine reference genome now align accurately to the non-reference sequences. We show that the non-reference sequences contain polymorphic sites that segregate within and between breeds of cattle. Our efforts to uncover novel functional sequences from a multi-assembly graph pave the way towards the transition to a more representative bovine reference genome.

genomics↗

bioRxiv2020

Duplication accelerates the evolution of structural complexity in protein quaternary structure

Gene duplication, from single genes to whole genomes, has been observed in organisms across all taxa. Despite its prevalence, the evolutionary benefits of this mechanism are the subject of ongoing debate. Gene duplication can significantly alter the self-assembly of protein quaternary structures, impacting the dosage or interaction proclivity. Here we use a lattice model of self-assembly as a coarse-grained representation of protein complex assembly, and show that it can be used to examine potential evolutionary advantages of duplication. Duplication provides a unique mechanism for increasing the evolvability of protein complexes by enabling the transformation of symmetric homomeric interactions into heteromeric ones. This transformation is extensively observed in in silico evolutionary simulations of the lattice model, with duplication events significantly accelerating the rate at which structural complexity increases. These coarse-grained simulation results are corroborated with a large-scale analysis of complexes from the Protein Data Bank.

bioinformatics↗

bioRxiv2019

Evolution of interface binding strengths in simplified model of protein quaternary structure

The self-assembly of proteins into protein quaternary structures is of fundamental importance to many biological processes, and protein misassembly is responsible for a wide range of proteopathic diseases. In recent years, abstract lattice models of protein self-assembly have been used to simulate the evolution and assembly of protein quaternary structure, and to provide a tractable way to study the genotype-phenotype map of such systems. Here we generalize these models by representing the interfaces as mutable binary strings. This simple change enables us to model the evolution of interface strengths, interface symmetry, and deterministic assembly pathways. Using the generalized model we are able to reproduce two important results established for real protein complexes: The first is that protein assembly pathways are under evolutionary selection to minimize misassembly. The second is that the assembly pathway of a complex mirrors its evolutionary history, and that both can be derived from the relative strengths of interfaces. These results demonstrate that the generalized lattice model offers a powerful new framework for the study of protein self-assembly processes and their evolution.

evolutionary biology↗