Molecular Mycology and Emerging Fungal Pathogens
Johan A. Maertens, Kieren A. Marr in Diagnosis of Fungal Infections, 2007
What makes a gene useful for molecular phylogeny? First, the gene should be present in all organisms under study, and this requirement forces one to select genes with essential cellular functions, such as ribosomal RNA genes. Second, the gene should serve as a molecular clock, with increasing evolutionary time since two organisms shared a common ancestor ticked off as accumulated nucleotide changes in the gene. If two organisms are close evolutionary cousins, then their genes should share a high degree of sequence similarity. If two organisms are distant evolutionary kin, then their genes should have been subjected to additional mutation and selection over this time period, witha resulting lower rate of sequence similarity noted. The application of molecular phylogenetic methods to some long-standing problems in mycology helps to illustrate this point.
Of what are epidemics the symptom?
Ann H. Kelly, Frédéric Keck, Christos Lynteris in The Anthropology of Epidemics, 2019
Molecular phylogenies are increasingly called upon to track the spread of epidemics, illuminate transmission dynamics, and pinpoint epidemic origins (for Ebola see Georges-Courbot 1997, for the earliest example). Assumptions embedded in the construction of molecular family trees (phylogenies) have been called into question. The first is the assumption of homogenous evolutionary time, the so-called ‘molecular clock’, such that mutations are assumed to occur at a steady rate over time. This is at odds with theories of ‘quantum evolution’, such that rates of evolution can vary significantly, particularly in times of accelerated environmental change such as those often associated with the emergence of epidemics. Another assumption is that bursts of differentiation that lead to new family lines being founded are associated with specific ‘real world’ events, such as cross-species transmission known as zoonotic events. These controversies regarding the interpretation of molecular traces benefit from triangulation with historical and ethnographic sources to ascertain their plausibility.
Intrinsic Biological Aging As Underlying Pathogenetic Mechanisms in Dementias of the Alzheimer’s Type
Zaven S. Khachaturian, Teresa S. Radebaugh in Alzheimer’s Disease, 2019
It is not easy to differentiate between processes that merely reflect the passage of chronological time and processes that reflect intrinsic biological aging. The latter could be defined as processes whose kinetics are appropriately correlated with the maximum life span potentials of taxonomically related groups of organisms, member species of which differ in their life-span potentials. An example of a molecular clock whose rate constants probably do not differ substantially among mammalian species is the racemization of certain optically active amino acids, such as aspartic acid, in homologous proteins with very low turnovers, such as dental enamel. For such proteins, there is a steady rate constant of transition from the l- to the d-enantiomer. By contrast, the rates of accumulation of carbonyl groups in various proteins probably do vary significantly among mammals, presumably reflecting differing susceptibilities to oxidative damage. This view is supported by evidence of intraspecific variations in the rates of accumulation of this marker for oxidative damage to proteins; cultured somatic cells from human subjects suffering from certain progeroid mutations (the Werner syndrome and the Hutchinson-Gilford syndrome) exhibit accelerated rates of such posttranslational alterations of their proteins.
Study of mutation from DNA to biological evolution
Published in International Journal of Radiation Biology, 2019
Masako Bando, Tetsuhiro Kinugawa, Yuichiro Manabe, Miwako Masugi, Hiroo Nakajima, Kazuyo Suzuki, Yuichi Tsunoyama, Takahiro Wada, Hiroshi Toki
Finally, we would like to mention an amazing numerical consistency between the cell-level evolutionary changes and polymorphisms within various species. Such an approach was first proposed by Kimura (1968) by investigating the DNA sequence of the amino acid and by counting the mutant substitutions. This approach made a remarkable breakthrough in the sense that it bridges the mutation of cells occurring in the 10 μm scale world and the theory of biological evolution in the world of the scale of billion years. This fact encourages us to proceed further to arrive at the concept of so-called molecular clock or evolutionary clock. This provides us a tool to connect the phylogenetic events to spontaneous mutation frequency and to estimate the time interval of phylogenetic events. Especially much progress has been made in DNA-sequencing technologies, the usage of the idea ‘molecular clock’ has become more valuable and access the development of theories of molecular evolution (Kumar 2005). Although we have not yet arrived at a complete understanding level on the interplay of the mutation rate, molecular evolution and evolution of living system and molecular clock, it will surely give various hints to solve the question, ‘what is life’ (Kumar and Subramanian 2002).
One future of clinical metagenomic sequencing for infectious diseases
Published in Expert Review of Molecular Diagnostics, 2019
Ryan C. Shean, Alexander L. Greninger
Current diagnostic mNGS approaches also often fail to take advantage of the single nucleotide resolution data provided by metagenomics. These data can be instantaneously fed back to the growing hive of data to perform detailed epidemiological analyses that help prevent infectious disease transmission. Such ‘excess data’ approaches to clinical sequence data are already being used with HIV genotypic resistance data and are likely to become a major thrust of current federal plans to reduce HIV transmission [15]. Widespread adoption of mNGS for diagnostic purposes would significantly accelerate this process, creating mounds of sequence data that could be mined for transmission patterns for preventative purposes. The full viral genomes that mNGS provides can create highly accurate transmission maps which can be invaluable especially in the context of an outbreak in the healthcare setting [16]. Future expansions of the relevant databases will allow much more fine-tuned molecular clock analysis and further increase the utility of these types of studies. Furthermore, mNGS techniques can also be easily modified for use with almost any organism, including those that have not been previously sequenced, allowing for both rapid and flexible transmission cluster tracking.
COVID-19 infection at nighttime
Published in Chronobiology International, 2020
Akio Fujimura, Kentaro Ushijima, Michael H. Smolensky
It is assumed a priori the probability of becoming infected and the severity of infection by COVID-19 does not vary as to when exposure occurs during the 24 h. Such an assumption may be invalid and lead to unnecessary risks. Biological processes, including those of the immune and organ systems, are highly organized in time as circadian and other endogenous rhythms. Circadian rhythms, in particular, are controlled by a molecular clock system – a master clock located in the hypothalamic suprachiasmatic nucleus of the brain and a multitude of peripheral clocks located in cells and tissues (Weaver 2016). The molecular clocks system is composed of several so-called clock genes, each expressed in a predictable-in-time manner during the 24 h. One of these genes – Bmal1 (brain and muscle ARNT-like1) (Weaver 2016) – shows relevance to the susceptibility and resistance to infection. Bmal1 exerts direct suppressive effect on the inflammatory response of myeloid cells; therefore, rhythmic repression of inflammatory genes by Bmal1 is critical for achieving an appropriate balance of inflammatory reactions (de Juan et al. 2016).