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All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Genetic Subtypes and Natural Resistance Mutations in HCV Genotype 4 Infected Saudi Arabian Patients

This study aimed to characterize the HCV genetic subtypes variability and the presence of natural occurring resistance-associated substitutions (RASs) in Saudi Arabia patients. A total of 17 GT patients were analyzed. Sequence analysis of NS3, NS5A, and NS5B regions was performed by direct sequencing, and phylogenetic analyses were used to determine genetic subtypes, RAS, and polymorphisms. Nine patients were infected by GT 4a, two with GT 4o and three with GT 4d. Two patients were infected with apparent recombinant virus (4a/4o/4a in NS3/NS5A/NS5B), and one patient was infected with a previously unknown, unclassifiable, virus of GT 4. Natural RASs were found in six patients (35%), including three infected by GT 4a, two by GT 4a/GT 4o/GT 4a, and one patient infected by an unknown, unclassifiable, virus of GT 4. In particular, NS3-RAS V170I was demonstrated in three patients, while NS5A-RASs (L28M, L30R, L28M + M31L) were detected in the remaining three patients. All patients were treated with sofosbuvir plus daclatasvir; three patients were lost to follow-up, whereas 14 patients completed the treatment. A sustained virological response (SVR) was obtained in all but one patient carrying NS3-RAS V170I who later relapsed. GT 4a is the most common subtype in this small cohort of Saudi Arabia patients infected with hepatitis C infection. Natural RASs were observed in about one-third of patients, but only one of them showed a treatment failure.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Microbiome characterization by high-throughput transfer RNA sequencing and modification analysis

Advances in high-throughput sequencing have facilitated remarkable insights into the diversity and functioning of naturally occurring microbes; however, current sequencing strategies are insufficient to reveal physiological states of microbial communities associated with protein translation dynamics. Transfer RNAs (tRNAs) are core components of protein synthesis machinery, present in all living cells, and are phylogenetically tractable, which make them ideal targets to gain physiological insights into environmental microbes. Here we report a direct sequencing approach, tRNA-seq, and a software suite, tRNA-seq-tools, to recover sequences, abundance profiles, and post-transcriptional modifications of microbial tRNA transcripts. Our analysis of cecal samples using tRNA-seq distinguishes high-fat-and low-fat-fed mice in a comparable fashion to 16S ribosomal RNA gene amplicons, and reveals taxon- and diet-dependent variations in tRNA modifications. Our results provide taxon-specific in situ insights into the dynamics of tRNA gene expression and post-transcriptional modifications within complex environmental microbiomes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Vanderwaltozyma urihicola sp. nov., a yeast species isolated from rotting wood and beetles in a Brazilian Amazonian rainforest biome

Five yeast isolates belonging to a candidate for novel species were obtained from rotting wood and the gut of a passalid beetle larva in a site of Amazonian rainforest biome in Brazil. Sequence analysis of the Internal Transcribed Spacer (ITS)-5.8S region and the D1/D2 domains of the large subunit rRNA gene showed that the isolates represent a novel species of the genus Vanderwaltozyma. The closest relative of the novel species is Vanderwaltozyma huisunica. These species differs due to 44 nt substitutions and 21 indels in the sequences of the ITS region, as well as by 15 substitutions and four indels in the sequences of the D1/D2 domains. A phylogenomic analysis of the Vanderwaltozyma species with genomes sequenced showed that this novel species is an outgroup to the other species of this genus. We propose the name Vanderwaltozyma urihicola sp. nov. (CBS 18107T, MycoBank MB 856975) to accommodate these isolates. Furthermore, the species is homothallic, producing one to two ascospores per ascus. The habitat of V. urihicola is rotting wood in the Brazilian Amazonian rainforest biome.

Amazonian Forest↗
DOE OSTI2016

Molecular cloning, genomic organization, chromosome mapping, tissues expression pattern and identification of a novel splicing variant of porcine CIDEb gene

Cell death-inducing DNA fragmentation factor-α-like effector b (CIDEb) is a member of the CIDE family of apoptosis-inducing factors, CIDEa and CIDEc have been reported to be Lipid droplets (LDs)-associated proteins that promote atypical LD fusion in adipocytes, and responsible for liver steatosis under fasting and obese conditions, whereas CIDEb promotes lipid storage under normal diet conditions [1], and promotes the formation of triacylglyceride-enriched VLDL particles in hepatocytes [2]. Here, we report the gene cloning, chromosome mapping, tissue distribution, genetic expression analysis, and identification of a novel splicing variant of the porcine CIDEb gene. Sequence analysis shows that the open reading frame of the normal porcine CIDEb isoform covers 660bp and encodes a 219-amino acid polypeptide, whereas its alternative splicing variant encodes a 142-amino acid polypeptide truncated at the fourth exon and comprised of the CIDE-N domain and part of the CIDE-C domain. The deduced amino acid sequence of normal porcine CIDEb shows an 85.8% similarity to the human protein and 80.0% to the mouse protein. The CIDEb genomic sequence spans approximately 6KB comprised of five exons and four introns. Radiation hybrid mapping demonstrated that porcine CIDEb is located at chromosome 7q21 and at a distance of 57cR from the most significantly linked marker, S0334, regions that are syntenic with the corresponding region in the human genome. Tissue expression analysis indicated that normal CIDEb mRNA is ubiquitously expressed in many porcine tissues. It was highly expressed in white adipose tissue and was observed at relatively high levels in the liver, lung, small intestine, lymphatic tissue and brain. The normal version of CIDEb was the predominant form in all tested tissues, whereas the splicing variant was expressed at low levels in all examined tissues except the lymphatic tissue. Furthermore, genetic expression analysis indicated that CIDEb mRNA levels were significantly higher in the white adipose tissue of lean pigs than their obese counterparts, in contrast to porcine CIDEa and CIDEc [3]. We therefore speculate that CIDEb may play a contrary role to the other CIDEs. The basic molecular information we provide here will be useful for further investigations of the physiological function of the gene, which will be helpful in better understanding the role of the CIDE family in lipid metabolism in pig models.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Criticality Evaluation of Low Density Product Oxides for Air Transport for the ES-3100 Package

This document presents the criticality safety evaluation of the Y-12 National Security Complex (Y-12) Model ES-3100 package for the addition of lower bulk density limits for HEU product oxides transported by air. The current authorized oxide density range for air transport is 2.0 to 6.54 g/cm 3 . The analysis in this report looks at lower densities, specifically in the range of 1.0 to 2.0 g/cm 3 . For reasons presented in this report, it was decided to present the entire range of oxide densities (1.0 to 6.54 g/cm 3 ) as a series of sub-ranges. The lowest density in each range was evaluated. Thus calculations were performed for the following oxide densities: 5.0 g/cm 3 , 4.0 g/cm 3 , 3.0 g/cm 3 , 2.0 g/cm 3 , 1.5 g/cm 3 and 1.0 g/cm 3 . Calculations presented herein were performed using a third generation computing platform; the Microway Parallel Linux Cluster ENGHPC workstation using the Monte Carlo Criticality Safety Analysis Sequence (CSAS5) criticality code sequence and 238-group ENDF/B-VII cross-section library of Standardized Computer Analysis for Licensing Evaluation (SCALE) 6.1.3 (ORNL/TM-2005/39, SCALE: A Comprehensive Modeling and Simulation Suite for Nuclear Safety Analysis and Design).

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2022

Benchmark datasets for SARS-CoV-2 surveillance bioinformatics

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has spread globally and is being surveilled with an international genome sequencing effort. Surveillance consists of sample acquisition, library preparation, and whole genome sequencing. This has necessitated a classification scheme detailing Variants of Concern (VOC) and Variants of Interest (VOI), and the rapid expansion of bioinformatics tools for sequence analysis. These bioinformatic tools are means for major actionable results: maintaining quality assurance and checks, defining population structure, performing genomic epidemiology, and inferring lineage to allow reliable and actionable identification and classification. Additionally, the pandemic has required public health laboratories to reach high throughput proficiency in sequencing library preparation and downstream data analysis rapidly. However, both processes can be limited by a lack of a standardized sequence dataset. We identified six SARS-CoV-2 sequence datasets from recent publications, public databases and internal resources. In addition, we created a method to mine public databases to identify representative genomes for these datasets. Using this novel method, we identified several genomes as either VOI/VOC representatives or non-VOI/VOC representatives. To describe each dataset, we utilized a previously published datasets format, which describes accession information and whole dataset information. Additionally, a script from the same publication has been enhanced to download and verify all data from this study.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Chameleon sequences in neurodegenerative diseases

Chameleon sequences can adopt either alpha helix sheet or a coil conformation. Defining chameleon sequences in PDB (Protein Data Bank) may yield to an insight on defining peptides and proteins responsible in neurodegeneration. In this research, we benefitted from the large PDB and performed a sequence analysis on Chameleons, where we developed an algorithm to extract peptide segments with identical sequences, but different structures. In order to find new chameleon sequences, we extracted a set of 8315 non-redundant protein sequences from the PDB with an identity less than 25%. Our data was classified to “helix to strand (HE)”, “helix to coil (HC)” and “strand to coil (CE)” alterations. We also analyzed the occurrence of singlet and doublet amino acids and the solvent accessibility in the chameleon sequences; we then sorted out the proteins with the most number of chameleon sequences and named them Chameleon Flexible Proteins (CFPs) in our dataset. Our data revealed that Gly, Val, Ile, Tyr and Phe, are the major amino acids in Chameleons. We also found that there are proteins such as Insulin Degrading Enzyme IDE and GTP-binding nuclear protein Ran (RAN) with the most number of chameleons (640 and 405 respectively). These proteins have known roles in neurodegenerative diseases. Therefore it can be inferred that other CFP's can serve as key proteins in neurodegeneration, and a study on them can shed light on curing and preventing neurodegenerative diseases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Faecal microRNA as a biomarker of the activity and prognosis of inflammatory bowel diseases

Highlights: • There is a significant difference in faecal miRNA between healthy subjects and IBD. • Faecal miRNAs might indicate the severity of IBD activity and prognosis. • Faecal miRNAs affect the proliferative activities of the gut microbiota. Reasons underlying the individual differences in the clinical manifestations of inflammatory bowel diseases (IBD) and the mechanism by which the host screens the intestinal microbiota remain unclear. The presence of miRNA in faeces might be a potential clue into differences in gut microbiota among these patients. In this study, we analysed the differences in miRNA levels in faecal samples from 117 patients diagnosed with IBD. There was a significant difference in faecal miRNAs between healthy subjects and those with inactive IBD. Further analysis showed that some miRNAs might indicate the severity of IBD activity and prognosis. Sequencing analysis of the 16S RNA V4 region in faecal microbiota in these IBD patients revealed significant differences in the phylogenetic architecture between subjects with active or inactive IBD and between IBD patients and healthy subjects. Finally, in vitro studies showed that these differentially expressed miRNAs have different effects on the proliferative activity of the intestinal microorganisms Fusobacterium nucleatum (Fn), Escherichia coli (E. coli) and segmental filamentous bacteria (SFB). We observed the dynamic uptake of miRNA by these bacteria using flow cytometry. This study reveals a potential link between faecal miRNA, intestinal microbiota, IBD activity and prognosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Suppressor Mutations in Type II Secretion Mutants of Vibrio cholerae : Inactivation of the VesC Protease

The type II secretion system (T2SS) is a conserved transport pathway responsible for the secretion of a range of virulence factors by many pathogens, including Vibrio cholerae. Disruption of the T2SS genes in V. cholerae results in loss of secretion, changes in cell envelope function, and growth defects. While T2SS mutants are viable, high-throughput genomic analyses have listed these genes among essential genes. To investigate whether secondary mutations arise as a consequence of T2SS inactivation, we sequenced the genomes of six V. cholerae T2SS mutants with deletions or insertions in either the epsG, epsL, or epsM genes and identified secondary mutations in all mutants. Two of the six T2SS mutants contain distinct mutations in the gene encoding the T2SS-secreted protease VesC. Other mutations were found in genes coding for V. cholerae cell envelope proteins. Subsequent sequence analysis of the vesC gene in 92 additional T2SS mutant isolates identified another 19 unique mutations including insertions or deletions, sequence duplications, and single-nucleotide changes resulting in amino acid substitutions in the VesC protein. Analysis of VesC variants and the X-ray crystallographic structure of wild-type VesC suggested that all mutations lead to loss of VesC production and/or function. One possible mechanism by which V. cholerae T2SS mutagenesis can be tolerated is through selection of vesC-inactivating mutations, which may, in part, suppress cell envelope damage, establishing permissive conditions for the disruption of the T2SS. Other mutations may have been acquired in genes encoding essential cell envelope proteins to prevent proteolysis by VesC.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

NW-BRaVE T3 Hydroplane Project Close: Project Close-out for T3 Hydroplane Analysis

Thrust 3 of the Northwest Biopreparedness Research in a Virtual Environment was an expansive project including method development, sample collection and sequence analysis. The sampling occurred over a multi-year period to generate metagenomic datasets that inform cyanophage-picocyanobacterial interactions in the Salish Sea across a moderate timeframe and geographical range. Part of the thrust’s aim was to validate how much experimental structural and multiomics work in a model organism (Prochlorococcus Marinus, str. MED4) from thrusts 1 and 2 would carry over into a broader range of related organisms in the natural world, to address a fundamental question in scientific preparation for epidemics: whether and how much experimental information from known and experimentally tractable species can translate to actionable biological information in unknown species. In other words, thrust 3 aimed to find out whether the model organism experiments matter in terms of how organisms interact. This report updates work described in Johnson and Pollock 2025 (1).

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2019

Genome of Alaskapox Virus, A Novel Orthopoxvirus Isolated from Alaska

Since the eradication of smallpox, there have been increases in poxvirus infections and the emergence of several novel poxviruses that can infect humans and domestic animals. In 2015, a novel poxvirus was isolated from a resident of Alaska. Diagnostic testing and limited sequence analysis suggested this isolate was a member of the Orthopoxvirus (OPXV) genus but was highly diverged from currently known species, including Akhmeta virus. Here, we present the complete 210,797 bp genome sequence of the Alaska poxvirus isolate, containing 206 predicted open reading frames. Phylogenetic analysis of the conserved central region of the genome suggested the Alaska isolate shares a common ancestor with Old World OPXVs and is diverged from New World OPXVs. We propose this isolate as a member of a new OPXV species, Alaskapox virus (AKPV). The AKPV genome contained host range and virulence genes typical of OPXVs but lacked homologs of C4L and B7R, and the hemagglutinin gene contained a unique 120 amino acid insertion. Seven predicted AKPV proteins were most similar to proteins in non-OPXV Murmansk or NY_014 poxviruses. Genomic analysis revealed evidence suggestive of recombination with Ectromelia virus in two putative regions that contain seven predicted coding sequences, including the A-type inclusion protein.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Identification, evolution and functional characterization of two Zn CDF‐family transporters of the ectomycorrhizal fungus Suillus luteus

Summary Two genes, SlZnT1 and SlZnT2 , encoding Cation Diffusion Facilitator (CDF) family transporters were isolated from Suillus luteus mycelium by genome walking. Both gene models are very similar and phylogenetic analysis indicates that they are most likely the result of a recent gene duplication event. Comparative sequence analysis of the deduced proteins predicts them to be Zn transporters. This function was confirmed by functional analysis in yeast for SlZnT1 . SlZnT1 was able to restore growth of the highly Zn sensitive yeast mutant Δzrc1 and localized to the vacuolar membrane. Transformation of Δzrc1 yeast cells with SlZnT1 resulted in an increased accumulation of Zn compared to empty vector transformed Δzrc1 yeast cells and equals Zn accumulation in wild type yeast cells. We were not able to express functional SlZnT2 in yeast. In S. luteus , both SlZnT genes are constitutively expressed whatever the external Zn concentrations. A labile Zn pool was detected in the vacuoles of S. luteus free‐living mycelium. Therefore we conclude that SlZnT1 is indispensable for maintenance of Zn homeostasis by transporting excess Zn into the vacuole.

Ruytinx, Joske↗
DOE OSTI2014

Metazen – metadata capture for metagenomes

Background: As the impact and prevalence of large-scale metagenomic surveys grow, so does the acute need for more complete and standards compliant metadata. Metadata (data describing data) provides an essential complement to experimental data, helping to answer questions about its source, mode of collection, and reliability. Metadata collection and interpretation have become vital to the genomics and metagenomics communities, but considerable challenges remain, including exchange, curation, and distribution. Currently, tools are available for capturing basic field metadata during sampling, and for storing, updating and viewing it. These tools are not specifically designed for metagenomic surveys; in particular, they lack the appropriate metadata collection templates, a centralized storage repository, and a unique ID linking system that can be used to easily port complete and compatible metagenomic metadata into widely used assembly and sequence analysis tools. Results: Metazen was developed as a comprehensive framework designed to enable metadata capture for metagenomic sequencing projects. Specifically, Metazen provides a rapid, easy-to-use portal to encourage early deposition of project and sample metadata. Conclusion: Metazen is an interactive tool that aids users in recording their metadata in a complete and valid format. A defined set of mandatory fields captures vital information, while the option to add fields provides flexibility.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2013

Detection of Bacillus anthracis DNA in Complex Soil and Air Samples Using Next-Generation Sequencing

Bacillus anthracis is the potentially lethal etiologic agent of anthrax disease, and is a significant concern in the realm of biodefense. One of the cornerstones of an effective biodefense strategy is the ability to detect infectious agents with a high degree of sensitivity and specificity in the context of a complex sample background. The nature of the B. anthracis genome, however, renders specific detection difficult, due to close homology with B. cereus and B. thuringiensis. We therefore elected to determine the efficacy of next-generation sequencing analysis and microarrays for detection of B. anthracis in an environmental background. We applied next-generation sequencing to titrated genome copy numbers of B. anthracis in the presence of background nucleic acid extracted from aerosol and soil samples. We found next-generation sequencing to be capable of detecting as few as 10 genomic equivalents of B. anthracis DNA per nanogram of background nucleic acid. Detection was accomplished by mapping reads to either a defined subset of reference genomes or to the full GenBank database. Moreover, sequence data obtained from B. anthracis could be reliably distinguished from sequence data mapping to either B. cereus or B. thuringiensis. We also demonstrated the efficacy of a microbial census microarray in detecting B. anthracis in the same samples, representing a cost-effective and high-throughput approach, complementary to next-generation sequencing. Our results, in combination with the capacity of sequencing for providing insights into the genomic characteristics of complex and novel organisms, suggest that these platforms should be considered important components of a biosurveillance strategy.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2013

LINEBACkER: Bio-inspired Data Reduction Toward Real Time Network Traffic Analysis

Abstract—One essential component of resilient cyber applications is the ability to detect adversaries and protect systems with the same flexibility adversaries will use to achieve their goals. Current detection techniques do not enable this degree of flexibility because most existing applications are built using exact or regular-expression matching to libraries of rule sets. Further, network traffic defies traditional cyber security approaches that focus on limiting access based on the use of passwords and examination of lists of installed or downloaded programs. These approaches do not readily apply to network traffic occurring beyond the access control point, and when the data in question are combined control and payload data of ever increasing speed and volume. Manual analysis of network traffic is not normally possible because of the magnitude of the data that is being exchanged and the length of time that this analysis takes. At the same time, using an exact matching scheme to identify malicious traffic in real time often fails because the lists against which such searches must operate grow too large. In this work, we introduce an alternative method for cyber network detection based on similarity-measuring algorithms for gene sequence analysis. These methods are ideal because they were designed to identify similar but nonidentical sequences. We demonstrate that our method is generally applicable to the problem of network traffic analysis by illustrating its use in two different areas both based on different attributes of network traffic. Our approach provides a logical framework for organizing large collections of network data, prioritizing traffic of interest to human analysts, and makes it possible to discover traffic signatures without the bias introduced by expert-directed signature generation. Pattern recognition on reduced representations of network traffic offers a fast, efficient, and more robust way to detect anomalies.

Teuton, Jeremy R.↗
DOE OSTI2020

Herbaspirillum rubrisubalbicans as a Phytopathogenic Model to Study the Immune System of Sorghum bicolor

Herbaspirillum rubrisubalbicans is the causal agent of red stripe disease (RSD) and mottle stripe disease of sorghum and sugarcane, respectively. In all, 63 genotypes of Sorghum bicolor were inoculated with H. rubrisubalbicans, with 59 showing RSD symptoms. Quantitative trait loci (QTL) analysis in a recombinant inbred line (RIL) population identified several QTL associated with variation in resistance to RSD. RNA sequencing analysis identified a number of genes whose transcript levels were differentially regulated during H. rubrisubalbicans infection. Among those genes that responded to H. rubrisubalbicans inoculation were many involved in plant–pathogen interactions such as leucine-rich repeat receptors, mitogen-activated protein kinase 1, calcium-binding proteins, transcriptional factors (ethylene-responsive element binding factor), and callose synthase. Pretreatment of sorghum leaves with the pathogen-associated molecular pattern (PAMP) molecules flg22 and chitooctaose provided protection against subsequent challenge with the pathogen, suggesting that PAMP-triggered immunity plays an important role in the sorghum immunity response. These data present baseline information for the use of the genetically tractable H. rubrisubalbicans–sorghum pathosystem for the study of innate immunity and disease resistance in this important grain and bioenergy crop. Information gained from the use of this system is likely to be informative for other monocots, including those more intractable for experimental study (e.g., sugarcane).

Biochemistry & Molecular Biology↗
DOE OSTI2019

Evaluating the Effects of Missing Values and Mixed Data Types on Social Sequence Clustering Using t-SNE Visualization

© 2019 Association for Computing Machinery. The goal of this work is to investigate the impact of missing values in clustering joint categorical social sequences. Identifying patterns in sociodemographic longitudinal data is important in a number of social science settings. However, performing analytical operations, such as clustering on life course trajectories, is challenging due to the categorical and multidimensional nature of the data, their mixed data types, and corruption by missing and inconsistent values. Data quality issues were investigated previously on single variable sequences. To understand their effects on multivariate sequence analysis, we employ a dataset of mixed data types and missing values, a dissimilarity measure designed for joint categorical sequence data, together with dimensionality reduction methodologies in a systematic design of sequence clustering experiments. Given the categorical nature of our data, we employ an “edit” distance using optimal matching. Because each data record has multiple variables of different types, we investigate the impact of mixing these variables in a single dissimilarity measure. Between variables with binary values and those with multiple nominal values, we find that the ability to overcome missing data problems is more difficult in the nominal domain than in the binary domain. Additionally, alignment of leading missing values can result in systematic biases in dissimilarity matrices and subsequently introduce both artificial clusters and unrealistic interpretations of associated data domains. We demonstrate the usage of t-distributed stochastic neighborhood embedding to visually guide mitigation of such biases by tuning the missing value substitution cost parameter or determining an optimal sequence span.

Lazar, Alina↗
DOE OSTI2018

The 2.1 Å structure of protein F9 and its comparison to L1, two components of the conserved poxvirus entry-fusion complex

The poxvirus F9 protein is a component of the vaccinia virus entry fusion complex (EFC) which consists of 11 proteins. The EFC forms a unique apparatus among viral fusion proteins and complexes. We solved the atomic structure of the F9 ectodomain at 2.10Å. A structural comparison to the ectodomain of the EFC protein L1 indicated a similar fold and organization, in which a bundle of fve α-helices is packed against two pairs of β-strands. However, instead of the L1 myristoylation site and hydrophobic cavity, F9 possesses a protruding loop between α-helices α3 and α4 starting at Gly90. Gly90 is conserved in all poxviruses except Salmon gill poxvirus (SGPV) and Diachasmimorpha longicaudata entomopoxvirus. Phylogenetic sequence analysis of all Poxviridae F9 and L1 orthologs revealed the SGPV genome to contain the most distantly related F9 and L1 sequences compared to the vaccinia proteins studied here. The structural diferences between F9 and L1 suggest functional adaptations during evolution from a common precursor that underlie the present requirement for each protein.

59 BASIC BIOLOGICAL SCIENCES↗