scholarly journals Evolutionary trend toward kinetic stability in the folding trajectory of RNases H

2016 ◽  
Vol 113 (46) ◽  
pp. 13045-13050 ◽  
Author(s):  
Shion A. Lim ◽  
Kathryn M. Hart ◽  
Michael J. Harms ◽  
Susan Marqusee

Proper folding of proteins is critical to producing the biological machinery essential for cellular function. The rates and energetics of a protein’s folding process, which is described by its energy landscape, are encoded in the amino acid sequence. Over the course of evolution, this landscape must be maintained such that the protein folds and remains folded over a biologically relevant time scale. How exactly a protein’s energy landscape is maintained or altered throughout evolution is unclear. To study how a protein’s energy landscape changed over time, we characterized the folding trajectories of ancestral proteins of the ribonuclease H (RNase H) family using ancestral sequence reconstruction to access the evolutionary history between RNases H from mesophilic and thermophilic bacteria. We found that despite large sequence divergence, the overall folding pathway is conserved over billions of years of evolution. There are robust trends in the rates of protein folding and unfolding; both modern RNases H evolved to be more kinetically stable than their most recent common ancestor. Finally, our study demonstrates how a partially folded intermediate provides a readily adaptable folding landscape by allowing the independent tuning of kinetics and thermodynamics.

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1063
Author(s):  
Vincent G. Martinson

While the majority of symbiosis research is focused on bacteria, microbial eukaryotes play important roles in the microbiota and as pathogens, especially the incredibly diverse Fungi kingdom. The recent emergence of widespread pathogens in wildlife (bats, amphibians, snakes) and multidrug-resistant opportunists in human populations (Candida auris) has highlighted the importance of better understanding animal–fungus interactions. Regardless of their prominence there are few animal–fungus symbiosis models, but modern technological advances are allowing researchers to utilize novel organisms and systems. Here, I review a forgotten system of animal–fungus interactions: the beetle–fungus symbioses of Drugstore and Cigarette beetles with their symbiont Symbiotaphrina. As pioneering systems for the study of mutualistic symbioses, they were heavily researched between 1920 and 1970, but have received only sporadic attention in the past 40 years. Several features make them unique research organisms, including (1) the symbiont is both extracellular and intracellular during the life cycle of the host, and (2) both beetle and fungus can be cultured in isolation. Specifically, fungal symbionts intracellularly infect cells in the larval and adult beetle gut, while accessory glands in adult females harbor extracellular fungi. In this way, research on the microbiota, pathogenesis/infection, and mutualism can be performed. Furthermore, these beetles are economically important stored-product pests found worldwide. In addition to providing a historical perspective of the research undertaken and an overview of beetle biology and their symbiosis with Symbiotaphrina, I performed two analyses on publicly available genomic data. First, in a preliminary comparative genomic analysis of the fungal symbionts, I found striking differences in the pathways for the biosynthesis of two B vitamins important for the host beetle, thiamine and biotin. Second, I estimated the most recent common ancestor for Drugstore and Cigarette beetles at 8.8–13.5 Mya using sequence divergence (CO1 gene). Together, these analyses demonstrate that modern methods and data (genomics, transcriptomes, etc.) have great potential to transform these beetle–fungus systems into model systems again.


Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1790
Author(s):  
Xuhua Xia

All dating studies involving SARS-CoV-2 are problematic. Previous studies have dated the most recent common ancestor (MRCA) between SARS-CoV-2 and its close relatives from bats and pangolins. However, the evolutionary rate thus derived is expected to differ from the rate estimated from sequence divergence of SARS-CoV-2 lineages. Here, I present dating results for the first time from a large phylogenetic tree with 86,582 high-quality full-length SARS-CoV-2 genomes. The tree contains 83,688 genomes with full specification of collection time. Such a large tree spanning a period of about 1.5 years offers an excellent opportunity for dating the MRCA of the sampled SARS-CoV-2 genomes. The MRCA is dated 16 August 2019, with the evolutionary rate estimated to be 0.05526 mutations/genome/day. The Pearson correlation coefficient (r) between the root-to-tip distance (D) and the collection time (T) is 0.86295. The NCBI tree also includes 10 SARS-CoV-2 genomes isolated from cats, collected over roughly the same time span as human COVID-19 infection. The MRCA from these cat-derived SARS-CoV-2 is dated 30 July 2019, with r = 0.98464. While the dating method is well known, I have included detailed illustrations so that anyone can repeat the analysis and obtain the same dating results. With 16 August 2019 as the date of the MRCA of sampled SARS-CoV-2 genomes, archived samples from respiratory or digestive tracts collected around or before 16 August 2019, or those that are not descendants of the existing SARS-CoV-2 lineages, should be particularly valuable for tracing the origin of SARS-CoV-2.


Author(s):  
Asher D. Cutter

Chapter 5, “Genealogy in evolution,” introduces branching tree diagrams as an intuitive way to visualize the evolutionary relationships between alleles, haplotypes, individuals, and species. It describes the nomenclature of gene tree topologies, the stochasticity in tree shape across genes, and the notion of a most recent common ancestor. This chapter also covers reverse-time genealogical thinking with coalescent theory and how it integrates with predictions about nucleotide polymorphism and the site frequency spectrum. An overview of how phylogenies show between-species genealogical relationships is used to highlight the concepts of orthology and homoplasy, how to calculate and interpret different metrics of DNA sequence divergence, the role of ancestral polymorphism in creating distinct gene trees, the multiple mutational hits problem, and factors that influence calculations of the time to the most recent common ancestor for species trees versus gene trees. This chapter surveys how to think of evolution in terms of genealogies that relate gene copies within a species or among species, and how to connect ideas about gene trees to other ideas in molecular population genetics.


Genetics ◽  
1998 ◽  
Vol 150 (3) ◽  
pp. 1187-1198 ◽  
Author(s):  
Mikkel H Schierup ◽  
Xavier Vekemans ◽  
Freddy B Christiansen

Abstract Expectations for the time scale and structure of allelic genealogies in finite populations are formed under three models of sporophytic self-incompatibility. The models differ in the dominance interactions among the alleles that determine the self-incompatibility phenotype: In the SSIcod model, alleles act codominantly in both pollen and style, in the SSIdom model, alleles form a dominance hierarchy, and in SSIdomcod, alleles are codominant in the style and show a dominance hierarchy in the pollen. Coalescence times of alleles rarely differ more than threefold from those under gametophytic self-incompatibility, and transspecific polymorphism is therefore expected to be equally common. The previously reported directional turnover process of alleles in the SSIdomcod model results in coalescence times lower and substitution rates higher than those in the other models. The SSIdom model assumes strong asymmetries in allelic action, and the most recessive extant allele is likely to be the most recent common ancestor. Despite these asymmetries, the expected shape of the allele genealogies does not deviate markedly from the shape of a neutral gene genealogy. The application of the results to sequence surveys of alleles, including interspecific comparisons, is discussed.


Author(s):  
Wenjun Cheng ◽  
Tianjiao Ji ◽  
Shuaifeng Zhou ◽  
Yong Shi ◽  
Lili Jiang ◽  
...  

AbstractEchovirus 6 (E6) is associated with various clinical diseases and is frequently detected in environmental sewage. Despite its high prevalence in humans and the environment, little is known about its molecular phylogeography in mainland China. In this study, 114 of 21,539 (0.53%) clinical specimens from hand, foot, and mouth disease (HFMD) cases collected between 2007 and 2018 were positive for E6. The complete VP1 sequences of 87 representative E6 strains, including 24 strains from this study, were used to investigate the evolutionary genetic characteristics and geographical spread of E6 strains. Phylogenetic analysis based on VP1 nucleotide sequence divergence showed that, globally, E6 strains can be grouped into six genotypes, designated A to F. Chinese E6 strains collected between 1988 and 2018 were found to belong to genotypes C, E, and F, with genotype F being predominant from 2007 to 2018. There was no significant difference in the geographical distribution of each genotype. The evolutionary rate of E6 was estimated to be 3.631 × 10-3 substitutions site-1 year-1 (95% highest posterior density [HPD]: 3.2406 × 10-3-4.031 × 10-3 substitutions site-1 year-1) by Bayesian MCMC analysis. The most recent common ancestor of the E6 genotypes was traced back to 1863, whereas their common ancestor in China was traced back to around 1962. A small genetic shift was detected in the Chinese E6 population size in 2009 according to Bayesian skyline analysis, which indicated that there might have been an epidemic around that year.


Author(s):  
Ya-Fang Hu ◽  
Li-Ping Jia ◽  
Fang-Yuan Yu ◽  
Li-Ying Liu ◽  
Qin-Wei Song ◽  
...  

Abstract Background Coxsackievirus A16 (CVA16) is one of the major etiological agents of hand, foot and mouth disease (HFMD). This study aimed to investigate the molecular epidemiology and evolutionary characteristics of CVA16. Methods Throat swabs were collected from children with HFMD and suspected HFMD during 2010–2019. Enteroviruses (EVs) were detected and typed by real-time reverse transcription-polymerase chain reaction (RT-PCR) and RT-PCR. The genotype, evolutionary rate, the most recent common ancestor, population dynamics and selection pressure of CVA16 were analyzed based on viral protein gene (VP1) by bioinformatics software. Results A total of 4709 throat swabs were screened. EVs were detected in 3180 samples and 814 were CVA16 positive. More than 81% of CVA16-positive children were under 5 years old. The prevalence of CVA16 showed obvious periodic fluctuations with a high level during 2010–2012 followed by an apparent decline during 2013–2017. However, the activities of CVA16 increased gradually during 2018–2019. All the Beijing CVA16 strains belonged to sub-genotype B1, and B1b was the dominant strain. One B1c strain was detected in Beijing for the first time in 2016. The estimated mean evolutionary rate of VP1 gene was 4.49 × 10–3 substitution/site/year. Methionine gradually fixed at site-23 of VP1 since 2012. Two sites were detected under episodic positive selection, one of which (site-223) located in neutralizing linear epitope PEP71. Conclusions The dominant strains of CVA16 belonged to clade B1b and evolved in a fast evolutionary rate during 2010–2019 in Beijing. To provide more favorable data for HFMD prevention and control, it is necessary to keep attention on molecular epidemiological and evolutionary characteristics of CVA16.


Genetics ◽  
1999 ◽  
Vol 151 (3) ◽  
pp. 1217-1228 ◽  
Author(s):  
Carsten Wiuf ◽  
Jotun Hein

Abstract In this article we discuss the ancestry of sequences sampled from the coalescent with recombination with constant population size 2N. We have studied a number of variables based on simulations of sample histories, and some analytical results are derived. Consider the leftmost nucleotide in the sequences. We show that the number of nucleotides sharing a most recent common ancestor (MRCA) with the leftmost nucleotide is ≈log(1 + 4N Lr)/4Nr when two sequences are compared, where L denotes sequence length in nucleotides, and r the recombination rate between any two neighboring nucleotides per generation. For larger samples, the number of nucleotides sharing MRCA with the leftmost nucleotide decreases and becomes almost independent of 4N Lr. Further, we show that a segment of the sequences sharing a MRCA consists in mean of 3/8Nr nucleotides, when two sequences are compared, and that this decreases toward 1/4Nr nucleotides when the whole population is sampled. A measure of the correlation between the genealogies of two nucleotides on two sequences is introduced. We show analytically that even when the nucleotides are separated by a large genetic distance, but share MRCA, the genealogies will show only little correlation. This is surprising, because the time until the two nucleotides shared MRCA is reciprocal to the genetic distance. Using simulations, the mean time until all positions in the sample have found a MRCA increases logarithmically with increasing sequence length and is considerably lower than a theoretically predicted upper bound. On the basis of simulations, it turns out that important properties of the coalescent with recombinations of the whole population are reflected in the properties of a sample of low size.


Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 482
Author(s):  
Alice Michie ◽  
John S. Mackenzie ◽  
David W. Smith ◽  
Allison Imrie

Ross River virus (RRV) is the most medically significant mosquito-borne virus of Australia, in terms of human morbidity. RRV cases, characterised by febrile illness and potentially persistent arthralgia, have been reported from all Australian states and territories. RRV was the cause of a large-scale epidemic of multiple Pacific Island countries and territories (PICTs) from 1979 to 1980, involving at least 50,000 cases. Historical evidence of RRV seropositivity beyond Australia, in populations of Papua New Guinea (PNG), Indonesia and the Solomon Islands, has been documented. We describe the genomic characterisation and timescale analysis of the first isolate of RRV to be sampled from PNG to date. Our analysis indicates that RRV has evolved locally within PNG, independent of Australian lineages, over an approximate 40 year period. The mean time to most recent common ancestor (tMRCA) of the unique PNG clade coincides with the initiation of the PICTs epidemic in mid-1979. This may indicate that an ancestral variant of the PNG clade was seeded into the region during the epidemic, a period of high RRV transmission. Further epidemiological and molecular-based surveillance is required in PNG to better understand the molecular epidemiology of RRV in the general Australasian region.


2010 ◽  
Vol 7 (11) ◽  
pp. 3387-3402 ◽  
Author(s):  
S. Trajanovski ◽  
C. Albrecht ◽  
K. Schreiber ◽  
R. Schultheiß ◽  
T. Stadler ◽  
...  

Abstract. Ancient Lake Ohrid on the Balkan Peninsula is considered to be the oldest ancient lake in Europe with a suggested Plio-/Pleistocene age. Its exact geological age, however, remains unknown. Therefore, molecular clock data of Lake Ohrid biota may serve as an independent constraint of available geological data, and may thus help to refine age estimates. Such evolutionary data may also help unravel potential biotic and abiotic factors that promote speciation events. Here, mitochondrial sequencing data of one of the largest groups of endemic taxa in the Ohrid watershed, the leech genus Dina, is used to test whether it represents an ancient lake species flock, to study the role of potential horizontal and vertical barriers in the watershed for evolutionary events, to estimate the onset of diversification in this group based on molecular clock analyses, and to compare this data with data from other endemic species for providing an approximate time frame for the origin of Lake Ohrid. Based on the criteria speciosity, monophyly and endemicity, it can be concluded that Dina spp. from the Ohrid watershed, indeed, represents an ancient lake species flock. Lineage sorting of its species, however, does not seem to be complete and/or hybridization may occur. Analyses of population structures of Dina spp. in the Ohrid watershed indicate a horizontal zonation of haplotypes from spring and lake populations, corroborating the role of lake-side springs, particularly the southern feeder springs, for evolutionary processes in endemic Ohrid taxa. Vertical differentiation of lake taxa, however, appears to be limited, though differences between populations from the littoral and the profundal are apparent. Molecular clock analyses indicate that the most recent common ancestor of extant species of this flock is approximately 1.99 ± 0.83 million years (Ma) old, whereas the split of the Ohrid Dina flock from a potential sister taxon outside the lake is estimated at 8.30 ± 3.60 Ma. Comparisons with other groups of endemic Ohrid species indicated that in all cases, diversification within the watershed started ≤2 Ma ago. Thus, this estimate may provide information on a minimum age for the origin of Lake Ohrid. Maximum ages are less consistent and generally less reliable. But cautiously, a maximum age of 3 Ma is suggested. Interestingly, this time frame of approximately 2–3 Ma ago for the origin of Lake Ohrid, generated based on genetic data, well fits the time frame most often used in the literature by geologists.


Author(s):  
Ajay Jasra ◽  
Maria De Iorio ◽  
Marc Chadeau-Hyam

In this paper, we consider a simulation technique for stochastic trees. One of the most important areas in computational genetics is the calculation and subsequent maximization of the likelihood function associated with such models. This typically consists of using importance sampling and sequential Monte Carlo techniques. The approach proceeds by simulating the tree, backward in time from observed data, to a most recent common ancestor. However, in many cases, the computational time and variance of estimators are often too high to make standard approaches useful. In this paper, we propose to stop the simulation, subsequently yielding biased estimates of the likelihood surface. The bias is investigated from a theoretical point of view. Results from simulation studies are also given to investigate the balance between loss of accuracy, saving in computing time and variance reduction.


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