Biology subjects

Chase, M.

Publications and source records attributed to Chase, M..

4 recordsLinked to original sources

bioRxiv2022

Traditional phylogenetic models are insensitive to variations in the effective population size

A substitution represents the emergence and fixation of an allele in a population or species and is the fundamental event from which phylogenetic models of sequence evolution are devised. Because of the increasing availability of genomic sequences, we are now able to take advantage of intraspecific variability when reconstructing the tree of life. As a result, substitutions can be more realistically modeled as the product of mutation, selection, and genetic drift. However, it is still unclear whether this increased complexity affects our measures of evolutionary times and rates. This study seeks to answer this question by contrasting the traditional substitution model with a population genetic equivalent using data from 4385 individuals distributed across 179 populations and representing 17 species of animals, plants, and fungi. We found that when the population genetics dynamic is modeled via the substitution rates, the evolutionary times and rates of the two models are well correlated, suggesting that the phylogenetic model is able to capture the time and pace of its population counterpart. However, a closer inspection of this result showed that the traditional models largely ignore the effect of the effective population size, even when it is explicitly accounted for in the substitution rates. Our findings suggest that superimposing population-genetics results on the substitution rates is an effective strategy to study mutation and selection biases, while other data sources (e.g., life history traits or polymorphisms) may need to be additionally integrated to make the traditional substitution models sensitive to the impact of genetic drift. When combined with the known effect of ancestral population size on generating phylogenomic incongruence due to incomplete lineage sorting, our findings provide further evidence that unaccounted-for variations in the effective population size may be one of the primary causes of errors in phylogenetic analyses at shorter time scales.

evolutionary biology↗

bioRxiv2022

Integrating top-down and bottom-up approaches to understand the genetic architecture of speciation across a monkeyflower hybrid zone

Understanding the phenotypic and genetic architecture of reproductive isolation is a longstanding goal of speciation research. In many systems, candidate barrier traits and loci have been identified, but causal connections between them are rarely made. In this study, we combine top-down and bottom-up approaches with demographic modeling toward an integrated understanding of speciation across a monkeyflower hybrid zone. Previous work in this system suggests that pollinator-mediated reproductive isolation is a primary barrier to gene flow between two divergent red- and yellow-flowered ecotypes of Mimulus aurantiacus. Several candidate floral traits contributing to pollinator isolation have been identified, including a difference in flower color, which is caused primarily by a single large-effect locus (MaMyb2). Other anonymous SNP loci, potentially contributing to pollinator isolation, also have been identified, but their causal relationships remain untested. Here, we performed demographic analyses, which indicate that this hybrid zone formed by secondary contact, but that subsequent gene flow was restricted in a large fraction of the genome by barrier loci. Using a cline-based genome scan (our bottom-up approach), we demonstrate that candidate barrier loci are broadly distributed across the genome, rather than mapping to one or a few islands of speciation. A QTL analysis (our top-down approach) revealed most floral traits are highly polygenic, with little evidence that QTL co-localize, indicating that most traits are largely genetically independent. Finally, we find little convincing evidence for the overlap of QTL and candidate barrier loci, suggesting that some loci contribute to other forms of reproductive isolation. Our findings highlight the challenges of understanding the genetic architecture of reproductive isolation and reveal that barriers to gene flow aside from pollinator isolation may play an important role in this system.

genetics↗

bioRxiv2021

Sensitivity optimization of a rhodopsin-based fluorescent voltage indicator

The ability to optically image cellular transmembrane voltage at millisecond-timescale resolution can offer unprecedented insight into the function of living brains in behaving animals. The chemigenetic voltage indicator Voltron is bright and photostable, making it a favorable choice for long in vivo imaging of neuronal populations at cellular resolution. Improving the voltage sensitivity of Voltron would allow better detection of spiking and subthreshold voltage signals. We performed site saturation mutagenesis at 40 positions in Voltron and screened for increased {Delta}F/F0 in response to action potentials (APs) in neurons. Using a fully automated patch-clamp system, we discovered a Voltron variant (Voltron.A122D) that increased the sensitivity to a single AP by 65% compared to Voltron. This variant (named Voltron2) also exhibited approximately 3-fold higher sensitivity in response to sub-threshold membrane potential changes. Voltron2 retained the sub-millisecond kinetics and photostability of its predecessor, with lower baseline fluorescence. Introducing the same A122D substitution to other Ace2 opsin-based voltage sensors similarly increased their sensitivity. We show that Voltron2 enables improved sensitivity voltage imaging in mice, zebrafish and fruit flies. Overall, we have discovered a generalizable mutation that significantly increases the sensitivity of Ace2 rhodopsin-based sensors, improving their voltage reporting capability.

neuroscience↗

bioRxiv2020

Hundreds of nuclear and plastid loci yield insights into orchid relationships

Premise of the studyEvolutionary relationships in the species-rich Orchidaceae have historically relied on organellar DNA sequences and limited taxon sampling. Previous studies provided a robust plastid-maternal phylogenetic framework, from which multiple hypotheses on the drivers of orchid diversification have been derived. However, the extent to which the maternal evolutionary history of orchids is congruent with that of the nuclear genome has remained uninvestigated. MethodsWe inferred phylogenetic relationships from 294 low-copy nuclear genes sequenced/obtained using the Angiosperms353 universal probe set from 75 species representing 69 genera, 16 tribes and 24 subtribes. To test for topological incongruence between nuclear and plastid genomes, we constructed a tree from 78 plastid genes, representing 117 genera, 18 tribes and 28 subtribes and compared them using a co-phylogenetic approach. The phylogenetic informativeness and support of the Angiosperms353 loci were compared with those of the 78 plastid genes. Key ResultsPhylogenetic inferences of nuclear datasets produced highly congruent and robustly supported orchid relationships. Comparisons of nuclear gene trees and plastid gene trees using the latest co-phylogenetic tools revealed strongly supported phylogenetic incongruence in both shallow and deep time. Phylogenetic informativeness analyses showed that the Angiosperms353 genes were in general more informative than most plastid genes. ConclusionsOur study provides the first robust nuclear phylogenomic framework for Orchidaceae plus an assessment of intragenomic nuclear discordance, plastid-nuclear tree incongruence, and phylogenetic informativeness across the family. Our results also demonstrate what has long been known but rarely documented: nuclear and plastid phylogenetic trees are not fully congruent and therefore should not be considered interchangeable.

evolutionary biology↗