The evolution of host–parasite interactions as host lineages colonize new geographic regions and diversify over evolutionary time is poorly understood. To assess whether haemosporidian parasite ...diversity has changed during the diversification of an avian host, we surveyed the diversity and prevalence of blood parasite lineages (genera Plasmodium, Haemoproteus, and Leucocytozoon) across the range of the songbird genus Junco, which has diversified recently as it recolonized North America following the last glacial maximum ∼18,000 years ago. We report the diversity and prevalence of parasites in junco taxa sampled from Costa Rica to Canada, and examine the influence of local avian species richness in the prevalence and diversity of parasites in junco samples. We screened for parasites in each individual by sequencing a fragment of their cytochrome b gene, identifying the different lineages, and quantifying the prevalence per junco taxon and locality. Of 304 juncos sampled, 178 tested positive for 1 or more parasite genera (58.5% overall prevalence). We found high parasite diversity in genera Haemoproteus and Leucocytozoon and much lower diversity in Plasmodium. Among the 63 parasite lineages detected, 32 of which have not been previously described, we found generalist lineages with widespread but low prevalence in Junco, but also some that appear to have remained specialized on this genus as it diversified across North America over thousands of years. Our results suggest a range of parasitic strategies, ranging from specialized to generalist lineages within single parasite genera. LAY SUMMARY In this study we describe patterns of haemosporidian blood parasite diversity and prevalence across the range of the genus Junco. We surveyed blood parasites in 304 juncos from across the range, and looked at parasite prevalence and diversity. We found high parasite diversity in genera Haemoproteus and Leucocytozoon and much lower diversity in Plasmodium. Both the prevalence and diversity of Haemoproteus and Leucocytozoon were positively correlated with local avian species richness. We also found that some parasites are specialized on juncos, whereas others can also be found in other landbird species. Some parasites appear to have remained restricted to juncos even when the recolonization of North America caused juncos to adapt to many different habitats and even diversify into different evolutionary lineages. La evolución de las interacciones entre hospedadores y parásitos cuando linajes de hospedadores colonizan nuevas regiones geográficas y se diversifican a lo largo del tiempo evolutivo es un proceso poco conocido. Para determinar si la diversidad de parásitos hemosporidios ha cambiado durante la diversificación de su hospedador aviar, muestreamos la diversidad y prevalencia de linajes de parásitos sanguíneos (géneros Plasmodium, Haemoproteus y Leucocitozoon) a lo largo de la distribución del género paseriforme Junco, el cual se ha diversificado recientemente al recolonizar Norteamérica tras el último máximo glacial ocurrido hace unos 18.000 años. Reportamos la diversidad y prevalencia de parásitos en juncos muestreados desde Costa Rica hasta Canadá, y examinamos la influencia de la riqueza local de especies de aves sobre la prevalencia y diversidad de parásitos en muestras de juncos. Detectamos los parásitos en cada individuo secuenciando un fragmento de su gen Cyt-b, identificando los diferentes linajes, y cuantificando la prevalencia por taxon y por localidad. De los 304 juncos muestreados, 178 dieron positivo para uno o más géneros parásitos (58,5% de prevalencia total). Encontramos alta diversidad parasitaria en los géneros Haemoproteus y Leucocytozoon, y una diversidad mucho menor en Plasmodium. Entre los 63 linajes parasitarios detectados, 32 de los cuales no habían sido descritos previamente, encontramos linajes generalistas con amplia distribución pero baja prevalencia en juncos, pero también algunos que parecen haber permanecido especializados en este género aviar a medida que se diversificaba por Norteamérica a lo largo de miles de años. Nuestros resultados sugieren la existencia de un abanico de estrategias parasitarias, incluyendo desde linajes especializados a generalistas dentro de un mismo género hemosporidio.
Influenza A virus (IAV) is one of the major global public health concerns but the emerging resistance of IAV to currently available antivirals requires the need to identify potential alternatives. ...Polyphenol rich sugarcane extract (PRSE) is an extract prepared from the sugarcane plant Saccharum Officinarum. Herein we aimed to determine if PRSE had antiviral activity against IAV. We showed that treatment of IAV-infected cells with PRSE results in a dose-dependent inhibition of virus infection at concentrations that were non-cytotoxic. PRSE treatment limited the early stages of infection, reducing viral genome replication, mRNA transcription and viral protein expression. PRSE did not affect the ability of IAV to bind sialic acid or change the morphology of viral particles. Additionally, PRSE treatment attenuated the replication of multiple IAV strains of the H3N2 and H1N1 subtype. In conclusion, we show that PRSE displays antiviral activity against a broad range of IAV strains, in vitro.
The evolutionary divergence of island populations, and in particular the tempo and relative importance of neutral and selective factors, is of central interest to the study of speciation. The rate of ...phenotypic evolution upon island colonization can vary greatly among taxa, and cases of convergent evolution can further confound the inference of correct evolutionary histories. Given the potential lability of phenotypic characters, molecular dating of insular lineages analyzed in a phylogenetic framework provides a critical tool to test hypotheses of phenotypic divergence since colonization. The Guadalupe junco is the only insular form of the polymorphic dark-eyed junco (Junco hyemalis), and shares eye and plumage color with continental morphs, yet presents an enlarged bill and reduced body size. Here we use variation in mtDNA sequence, morphological traits and song variables to test whether the Guadalupe junco evolved rapidly following a recent colonization by a mainland form of the dark-eyed junco, or instead represents a well-differentiated "cryptic" lineage adapted to the insular environment through long-term isolation, with plumage coloration a result of evolutionary convergence. We found high mtDNA divergence of the island lineage with respect to both continental J. hyemalis and J. phaeonotus, representing a history of isolation of about 600,000 years. The island lineage was also significantly differentiated in morphological and male song variables. Moreover, and contrary to predictions regarding diversity loss on small oceanic islands, we document relatively high levels of both haplotypic and song-unit diversity on Guadalupe Island despite long-term isolation in a very small geographic area. In contrast to prevailing taxonomy, the Guadalupe junco is an old, well-differentiated evolutionary lineage, whose similarity to mainland juncos in plumage and eye color is due to evolutionary convergence. Our findings confirm the role of remote islands in driving divergence and speciation, but also their potential role as repositories of ancestral diversity.
Abstract
We evaluated the effects of sea surface temperature anomalies (SSTA) in the southern California Current Ecosystem on the annual Guadalupe fur seal (Arctocephalus townsendi) pup production, a ...species recovering from near extinction. Pup counts from 1991 to 1993 and from 2006 to 2019 were used to estimate deviations from a long-term trend as a proxy for the population's reproductive success. We estimated interannual SSTA as a subtraction from the linear trend spanning 1991–2019 for a 778,000 km2 area, which represents the primary foraging range of adult females. The long-term increase in pup production followed an exponential curve ( ${\rm{R}}_{\rm{B}}^2 = {\rm{\ }}1$), typical of species in a recovery phase. Pup production deviations from this trend responded to SSTA during the gestation period as a cubic polynomial function ( ${\rm{R}}_{\rm{B}}^2 = {\rm{\ }}0.837$), revealing that SSTA < −0.2°C and between ∼0.6 and 1.38°C increased pup production in the subsequent breeding season, whereas normal to slightly warm (−0.17 to 0.6°C) and extreme SSTA (>1.4°C) decreased pup counts, arguably resulting from low prey availability and quality. This model allowed us to estimate pup production for years without observations, needed to understand the environmental variability influence on the recovery process of this species, and therefore constitutes a practical tool for its conservation and management.
Mitochondria possess a small genome that codes for core subunits of the oxidative phosphorylation system and whose expression is essential for energy production. Information on the regulation and ...spatial organization of mitochondrial gene expression in the cellular context has been difficult to obtain. Here we devise an imaging approach to analyze mitochondrial translation within the context of single cells, by following the incorporation of clickable non‐canonical amino acids. We apply this method to multiple cell types, including specialized cells such as cardiomyocytes and neurons, and monitor with spatial resolution mitochondrial translation in axons and dendrites. We also show that translation imaging allows to monitor mitochondrial protein expression in patient fibroblasts. Approaching mitochondrial translation with click chemistry opens new avenues to understand how mitochondrial biogenesis is integrated into the cellular context and can be used to assess mitochondrial gene expression in mitochondrial diseases.
Synopsis
This study monitors mitochondrial protein synthesis with spatial resolution in single cells of multiple cell types.
Labelling of mitochondrial translation products allows to monitor translation with spatial resolution within single cells.
Mitochondria show different levels of protein synthesis within a single cell.
Protein synthesis occurs in mitochondria of the pre‐ and the postsynapse.
This study monitors mitochondrial protein synthesis with spatial resolution in single cells of multiple cell types.
Many epidemiologic studies have associated human mitochondrial haplogroups to rare mitochondrial diseases like Leber's hereditary optic neuropathy or to more common age-linked disorders such as ...Parkinson's disease. However, cellular, biochemical and molecular-genetic evidence that is able to explain these associations is very scarce. The etiology of multifactorial diseases is very difficult to sort out because such diseases are due to a combination of genetic and environmental factors that individually only contribute in small part to the development of the illness. Thus, the haplogroup-defining mutations might behave as susceptibility factors, but they could have only a small effect on oxidative phosphorylation (OXPHOS) function. Moreover, these effects would be highly dependent on the ‘context’ in which the genetic variant is acting. To homogenize this ‘context’ for mitochondrial DNA (mtDNA) mutations, a cellular approach is available that involves the use of what is known as ‘cybrids’. By using this model, we demonstrate that mtDNA and mtRNA levels, mitochondrial protein synthesis, cytochrome oxidase activity and amount, normalized oxygen consumption, mitochondrial inner membrane potential and growth capacity are different in cybrids from the haplogroup H when compared with those of the haplogroup Uk. Thus, these inherited basal differences in OXPHOS capacity can help to explain why some individuals more quickly reach the bioenergetic threshold below which tissue symptoms appear and progress toward multifactorial disorders. Hence, some population genetic variants in mtDNA contribute to the genetic component of complex disorders. The existence of mtDNA-based OXPHOS differences opens possibilities for the existence of a new field, mitochondrial pharmacogenomics. New sequence accession nos: HM103354–HM103363.
We previously described increased levels of growth and differentiation factor 15 (GDF-15) in skeletal muscle and serum of patients with mitochondrial diseases. Here we evaluated GDF-15 as a biomarker ...for mitochondrial diseases affecting children and compared it to fibroblast-growth factor 21 (FGF-21). To investigate the mechanism of GDF-15 induction in these pathologies we measured its expression and secretion in response to mitochondrial dysfunction.
We analysed 59 serum samples from 48 children with mitochondrial disease, 19 samples from children with other neuromuscular diseases and 33 samples from aged-matched healthy children. GDF-15 and FGF-21 circulating levels were determined by ELISA.
Our results showed that in children with mitochondrial diseases GDF-15 levels were on average increased by 11-fold (mean 4046pg/ml, 1492 SEM) relative to healthy (350, 21) and myopathic (350, 32) controls. The area under the curve for the receiver-operating-characteristic curve for GDF-15 was 0.82 indicating that it has a good discriminatory power. The overall sensitivity and specificity of GDF-15 for a cut-off value of 550pg/mL was 67.8% (54.4%-79.4%) and 92.3% (81.5%-97.9%), respectively. We found that elevated levels of GDF-15 and or FGF-21 correctly identified a larger proportion of patients than elevated levels of GDF-15 or FGF-21 alone. GDF-15, as well as FGF-21, mRNA expression and protein secretion, were significantly induced after treatment of myotubes with oligomycin and that levels of expression of both factors significantly correlated.
Our data indicate that GDF-15 is a valuable serum quantitative biomarker for the diagnosis of mitochondrial diseases in children and that measurement of both GDF-15 and FGF-21 improves the disease detection ability of either factor separately. Finally, we demonstrate for the first time that GDF-15 is produced by skeletal muscle cells in response to mitochondrial dysfunction and that its levels correlate in vitro with FGF-21 levels.
Human mitochondrial transcription factor A, TFAM, is essential for mitochondrial DNA packaging and maintenance and also has a crucial role in transcription. Crystallographic analysis of TFAM in ...complex with an oligonucleotide containing the mitochondrial light strand promoter (LSP) revealed two high-mobility group (HMG) protein domains that, through different DNA recognition properties, intercalate residues at two inverted DNA motifs. This induced an overall DNA bend of ~180°, stabilized by the interdomain linker. This U-turn allows the TFAM C-terminal tail, which recruits the transcription machinery, to approach the initiation site, despite contacting a distant DNA sequence. We also ascertained that structured protein regions contacting DNA in the crystal were highly flexible in solution in the absence of DNA. Our data suggest that TFAM bends LSP to create an optimal DNA arrangement for transcriptional initiation while facilitating DNA compaction elsewhere in the genome.
Heredity of familial hypercholesterolemia (FH) can present as a dominant monogenic disorder of polygenic origin or with no known genetic cause. In addition, the variability of the symptoms among ...individuals or within the same families evidence the potential contribution of additional factors than monogenic mutations that could modulate the development and severity of the disease. In addition, statins, the lipid-lowering drugs which constitute the first-line therapy for the disease, cause associated muscular symptoms in a certain number of individuals. Here, we analyze the evidence of the mitochondrial genetic variation with a special emphasis on the role of CoQ
to explain this variability found in both disease symptoms and statins side effects. We propose to use mtDNA variants and copy numbers as markers for the cardiovascular disease development of FH patients and to predict potential statin secondary effects and explore new mechanisms to identify new markers of disease or implement personalized medicine strategies for FH therapy.
Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease that typically causes bilateral blindness in young men. It is characterized by as yet undisclosed genetic and environmental ...factors affecting the incomplete penetrance.
We identified 27 LHON subjects who possess heteroplasmic primary LHON mutations. Mitochondrial DNA (mtDNA) copy number was evaluated.
The presence of centrocecal scotoma, an edematous, hyperemic optic nerve head, and vascular tortuosity, as well as telangiectasia was recognized in affected subjects. We found higher cellular mtDNA content in peripheral blood cells of unaffected heteroplasmic mutation carriers with respect to the affected.
The increase of cellular mtDNA content prevents complete loss of vision despite the presence of a heteroplasmic state of LHON primary mutation, suggesting that it is a key factor responsible for penetrance of LHON.
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