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"Foley, Nicole"
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Mammal madness: is the mammal tree of life not yet resolved?
2016
Most molecular phylogenetic studies place all placental mammals into four superordinal groups, Laurasiatheria (e.g. dogs, bats, whales), Euarchontoglires (e.g. humans, rodents, colugos), Xenarthra (e.g. armadillos, anteaters) and Afrotheria (e.g. elephants, sea cows, tenrecs), and estimate that these clades last shared a common ancestor 90–110 million years ago. This phylogeny has provided a framework for numerous functional and comparative studies. Despite the high level of congruence among most molecular studies, questions still remain regarding the position and divergence time of the root of placental mammals, and certain ‘hard nodes’ such as the Laurasiatheria polytomy and Paenungulata that seem impossible to resolve. Here, we explore recent consensus and conflict among mammalian phylogenetic studies and explore the reasons for the remaining conflicts. The question of whether the mammal tree of life is or can be ever resolved is also addressed.
This article is part of the themed issue ‘Dating species divergences using rocks and clocks’.
Journal Article
Evolutionary History of the Asian Horned Frogs (Megophryinae): Integrative Approaches to Timetree Dating in the Absence of a Fossil Record
2017
Molecular dating studies typically need fossils to calibrate the analyses. Unfortunately, the fossil record is extremely poor or presently nonexistent for many species groups, rendering such dating analysis difficult. One such group is the Asian horned frogs (Megophryinae). Sampling all generic nomina, we combined a novel ∼5 kb dataset composed of four nuclear and three mitochondrial gene fragments to produce a robust phylogeny, with an extensive external morphological study to produce a working taxonomy for the group. Expanding the molecular dataset to include out-groups of fossil-represented ancestral anuran families, we compared the priorless RelTime dating method with the widely used prior-based Bayesian timetree method, MCMCtree, utilizing a novel combination of fossil priors for anuran phylogenetic dating. The phylogeny was then subjected to ancestral phylogeographic analyses, and dating estimates were compared with likely biogeographic vicariant events. Phylogenetic analyses demonstrated that previously proposed systematic hypotheses were incorrect due to the paraphyly of genera. Molecular phylogenetic, morphological, and timetree results support the recognition of Megophryinae as a single genus, Megophrys, with a subgenus level classification. Timetree results using RelTime better corresponded with the known fossil record for the out-group anuran tree. For the priorless in-group, it also outperformed MCMCtree when node date estimates were compared with likely influential historical biogeographic events, providing novel insights into the evolutionary history of this pan-Asian anuran group. Given a relatively small molecular dataset, and limited prior knowledge, this study demonstrates that the computationally rapid RelTime dating tool may outperform more popular and complex prior reliant timetree methodologies.
Journal Article
Management of Peripheral T-cell Lymphomas and the Role of Transplant
2022
Purpose of ReviewHere, we review the management of peripheral T-cell lymphoma, particularly focusing on the role of autologous and allogeneic stem cell transplant. Recent FindingsPeripheral T-cell lymphomas are a rare subset of non-Hodgkin’s lymphomas that are treated with curative intent. While therapy has been based on other aggressive lymphoid malignancies, outcomes are generally poorer than B-cell lymphomas with 5-year overall and progression-free survival of 30–40% and 20–30%, respectively. In effort to improve outcomes, transplant has been used in both the frontline and salvage settings. Although not studied in randomized studies, consolidation with autologous stem cell transplant in first remission has been associated with an approximate 5-year overall survival of 50–60% and 5-year progression-free survival of 40–45%. Unfortunately, most patients relapse, and, in this setting, allogeneic transplant remains the only curative option for those who are transplant-eligible. Multiple series have now shown that 3-year overall survival with allogeneic transplant is approximately 60%. However, outcomes with transplant are associated with disease control at the time of transplant.SummaryIn contrast to B-cell malignancies, treatment decisions for peripheral T-cell lymphomas are supported mostly by phase II studies, retrospective series, and expert opinion. For patients with peripheral T-cell lymphoma able to achieve sufficient disease control, autologous stem cell transplantation in first remission and allogeneic stem cell transplantation in relapsed disease offer modest benefit over chemotherapy alone.
Journal Article
How and Why Overcome the Impediments to Resolution: Lessons from rhinolophid and hipposiderid Bats
by
Goodman, Steven M
,
Jacobs, David S
,
Puechmaille, Sébastien J
in
Bats
,
Comparative analysis
,
Coronaviridae
2015
The phylogenetic and taxonomic relationships among the Old World leaf-nosed bats (Hipposideridae) and the closely related horseshoe bats (Rhinolophidae) remain unresolved. In this study, we generated a novel approximately 10-kb molecular data set of 19 nuclear exon and intron gene fragments for 40 bat species to elucidate the phylogenetic relationships within the families Rhinolophidae and Hipposideridae. We estimated divergence times and explored potential reasons for any incongruent phylogenetic signal. We demonstrated the effects of outlier taxa and genes on phylogenetic reconstructions and compared the relative performance of intron and exon data to resolve phylogenetic relationships. Phylogenetic analyses produced a well-resolved phylogeny, supporting the familial status of Hipposideridae and demonstrated the paraphyly of the largest genus, Hipposideros. A fossil-calibrated timetree and biogeographical analyses estimated that Rhinolophidae and Hipposideridae diverged in Africa during the Eocene approximately 42 Ma. The phylogram, the timetree, and a unique retrotransposon insertion supported the elevation of the subtribe Rhinonycterina to family level and which is diagnosed herein. Comparative analysis of diversification rates showed that the speciose genera Rhinolophus and Hipposideros underwent diversification during the Mid-Miocene Climatic Optimum. The intron versus exon analyses demonstrated the improved nodal support provided by introns for our optimal tree, an important finding for large-scale phylogenomic studies, which typically rely on exon data alone. With the recent outbreak of Middle East respiratory syndrome, caused by a novel coronavirus, the study of these species is urgent as they are considered the natural reservoir for emergent severe acute respiratory syndrome (SARS)-like coronaviruses. It has been shown that host phylogeny is the primary factor that determines a virus’s persistence, replicative ability, and can act as a predictor of new emerging disease. Therefore, this newly resolved phylogeny can be used to direct future assessments of viral diversity and to elucidate the origin and development of SARS-like coronaviruses in mammals.
Journal Article
Tree House Explorer: A Novel Genome Browser for Phylogenomics
2022
Abstract
Tree House Explorer (THEx) is a genome browser that integrates phylogenomic data and genomic annotations into a single interactive platform for combined analysis. THEx allows users to visualize genome-wide variation in evolutionary histories and genetic divergence on a chromosome-by-chromosome basis, with continuous sliding window comparisons to gene annotations, recombination rates, and other user-specified, highly customizable feature annotations. THEx provides a new platform for interactive phylogenomic data visualization to analyze and interpret the diverse evolutionary histories woven throughout genomes. Hosted on Conda, THEx integrates seamlessly into new or pre-existing workflows.
Journal Article
Longitudinal comparative transcriptomics reveals unique mechanisms underlying extended healthspan in bats
2019
Bats are the longest-lived mammals, given their body size. However, the underlying molecular mechanisms of their extended healthspans are poorly understood. To address this question we carried out an eight-year longitudinal study of ageing in long-lived bats (
Myotis myotis
). We deep-sequenced ~1.7 trillion base pairs of RNA from 150 blood samples collected from known aged bats to ascertain the age-related transcriptomic shifts and potential microRNA-directed regulation that occurred. We also compared ageing transcriptomic profiles between bats and other mammals by analysis of 298 longitudinal RNA sequencing datasets. Bats did not show the same transcriptomic changes with age as commonly observed in humans and other mammals, but rather exhibited a unique, age-related gene expression pattern associated with DNA repair, autophagy, immunity and tumour suppression that may drive their extended healthspans. We show that bats have naturally evolved transcriptomic signatures that are known to extend lifespan in model organisms, and identify novel genes not yet implicated in healthy ageing. We further show that bats’ longevity profiles are partially regulated by microRNA, thus providing novel regulatory targets and pathways for future ageing intervention studies. These results further disentangle the ageing process by highlighting which ageing pathways contribute most to healthy ageing in mammals.
RNA-Seq analysis of an 8-year longitudinal study of long-lived bats reveals unique transcriptomic signatures and novel candidate genes associated with healthy ageing.
Journal Article
As Blind as a Bat? Opsin Phylogenetics Illuminates the Evolution of Color Vision in Bats
2019
Through their unique use of sophisticated laryngeal echolocation bats are considered sensory specialists amongst mammals and represent an excellent model in which to explore sensory perception. Although several studies have shown that the evolution of vision is linked to ecological niche adaptation in other mammalian lineages, this has not yet been fully explored in bats. Recent molecular analysis of the opsin genes, which encode the photosensitive pigments underpinning color vision, have implicated high-duty cycle (HDC) echolocation and the adoption of cave roosting habits in the degeneration of color vision in bats. However, insufficient sampling of relevant taxa has hindered definitive testing of these hypotheses. To address this, novel sequence data was generated for the SWS1 and MWS/LWS opsin genes and combined with existing data to comprehensively sample species representing diverse echolocation types and niches (SWS1 n = 115; MWS/LWS n = 45). A combination of phylogenetic analysis, ancestral state reconstruction, and selective pressure analyses were used to reconstruct the evolution of these visual pigments in bats and revealed that although both genes are evolving under purifying selection in bats, MWS/LWS is highly conserved but SWS1 is highly variable. Spectral tuning analyses revealed that MWS/LWS opsin is tuned to a long wavelength, 555–560 nm in the bat ancestor and the majority of extant taxa. The presence of UV vision in bats is supported by our spectral tuning analysis, but phylogenetic analyses demonstrated that the SWS1 opsin gene has undergone pseudogenization in several lineages. We do not find support for a link between the evolution of HDC echolocation and the pseudogenization of the SWS1 gene in bats, instead we show the SWS1 opsin is functional in the HDC echolocator, Pteronotus parnellii. Pseudogenization of the SWS1 is correlated with cave roosting habits in the majority of pteropodid species. Together these results demonstrate that the loss of UV vision in bats is more widespread than was previously considered and further elucidate the role of ecological niche specialization in the evolution of vision in bats.
Journal Article
Single-haplotype comparative genomics provides insights into lineage-specific structural variation during cat evolution
2023
The role of structurally dynamic genomic regions in speciation is poorly understood due to challenges inherent in diploid genome assembly. Here we reconstructed the evolutionary dynamics of structural variation in five cat species by phasing the genomes of three interspecies F1 hybrids to generate near-gapless single-haplotype assemblies. We discerned that cat genomes have a paucity of segmental duplications relative to great apes, explaining their remarkable karyotypic stability. X chromosomes were hotspots of structural variation, including enrichment with inversions in a large recombination desert with characteristics of a supergene. The X-linked macrosatellite
DXZ4
evolves more rapidly than 99.5% of the genome clarifying its role in felid hybrid incompatibility. Resolved sensory gene repertoires revealed functional copy number changes associated with ecomorphological adaptations, sociality and domestication. This study highlights the value of gapless genomes to reveal structural mechanisms underpinning karyotypic evolution, reproductive isolation and ecological niche adaptation.
Single-haplotype genome assemblies from five cat species shed light on the dynamics of structural variations during felid radiation and resolve sensory gene repertoires associated with adaptation and domestication.
Journal Article
Building capacity for testing sterile insect technique against Aedes-borne diseases in the Pacific: a training workshop and launch of sterile insect technique trials against Aedes aegypti and arboviral diseases
2024
Background
Vector-borne diseases cause morbidity and mortality globally. However, some areas are more impacted than others, especially with climate change. Controlling vectors remains the primary means to prevent these diseases, but new, more effective tools are needed. The World Health Organization (WHO) prioritized evaluating novel control methods, such as sterile insect technique (SIT) for control of
Aedes
-borne diseases. In response, a multiagency partnership between the U.S. Centers for Disease Control and Prevention (CDC), the Special Programme for Research and Training in Tropical Diseases (TDR), WHO, and the International Atomic Energy Agency (IAEA) supported the operational implementation and evaluation of SIT against
Aedes aegypti
and arboviral diseases in the Pacific through a consortium of regional partners (PAC-SIT Consortium).
Main text
A workshop was held from 2 to 6 May 2023, during which PAC-SIT country participants, researchers, and stakeholders in SIT, scientific advisory committee members, and organizational partners came together to review the principles and components of SIT, share experiences, visit field sites and the SIT facility, and officially launch the PAC-SIT project. Working in groups focused on entomology, epidemiology, and community engagement, participants addressed challenges, priorities, and needs for SIT implementation.
Conclusions
The PAC-SIT workshop brought together researchers and stakeholders engaged in evaluating SIT for arboviral diseases in the Pacific region and globally. This training workshop highlighted that many countries are actively engaged in building operational capacities and phased testing of SIT. The workshop identified a key need for robust larger-scale studies tied with epidemiological endpoints to provide evidence for the scalability and impact on mosquito-borne diseases.
Journal Article
Population level mitogenomics of long-lived bats reveals dynamic heteroplasmy and challenges the Free Radical Theory of Ageing
2018
Bats are the only mammals capable of true, powered flight, which drives an extremely high metabolic rate. The “Free Radical Theory of Ageing” (FTRA) posits that a high metabolic rate causes mitochondrial heteroplasmy and the progressive ageing phenotype. Contrary to this, bats are the longest-lived order of mammals given their small size and high metabolic rate. To investigate if bats exhibit increased mitochondrial heteroplasmy with age, we performed targeted, deep sequencing of mitogenomes and measured point heteroplasmy in wild, long lived
Myotis myotis
. Blood was sampled from 195 individuals, aged between <1 and at 6+ years old, and whole mitochondria deep-sequenced, with a subset sampled over multiple years. The majority of heteroplasmies were at a low frequency and were transitions. Oxidative mutations were present in only a small number of individuals, suggesting local oxidative stress events. Cohort data showed no significant increase in heteroplasmy with age, while longitudinal data from recaptured individuals showed heteroplasmy is dynamic, and does not increase uniformly over time. We show that bats do not suffer from the predicted, inevitable increase in heteroplasmy as posited by the FRTA, instead heteroplasmy was found to be dynamic, questioning its presumed role as a primary driver of ageing.
Journal Article