Co-occurrence Of Domains Research Articles

A systematic screen for co-option of transposable elements across the fungal kingdom

How novel protein functions are acquired is a central question in molecular biology. Key paths to novelty include gene duplications, recombination or horizontal acquisition. Transposable elements (TEs) are increasingly recognized as a major source of novel domain-encoding sequences. However, the impact of TE coding sequences on the evolution of the proteome remains understudied. Here, we analyzed 1237 genomes spanning the phylogenetic breadth of the fungal kingdom. We scanned proteomes for evidence of co-occurrence of TE-derived domains along with other conventional protein functional domains. We detected more than 13,000 predicted proteins containing potentially TE-derived domain, of which 825 were identified in more than five genomes, indicating that many host-TE fusions may have persisted over long evolutionary time scales. We used the phylogenetic context to identify the origin and retention of individual TE-derived domains. The most common TE-derived domains are helicases derived from Academ, Kolobok or Helitron. We found putative TE co-options at a higher rate in genomes of the Saccharomycotina, providing an unexpected source of protein novelty in these generally TE depleted genomes. We investigated in detail a candidate host-TE fusion with a heterochromatic transcriptional silencing function that may play a role in TE and gene regulation in ascomycetes. The affected gene underwent multiple full or partial losses within the phylum. Overall, our work establishes a kingdom-wide view of putative host-TE fusions and facilitates systematic investigations of candidate fusion proteins.

Co-occurrence of enzyme domains guides the discovery of an oxazolone synthetase.

Multidomain enzymes orchestrate two or more catalytic activities to carry out metabolic transformations with increased control and speed. Here, we report the design and development of a genome-mining approach for targeted discovery of biochemical transformations through the analysis of co-occurring enzyme domains (CO-ED) in a single protein. CO-ED was designed to identify unannotated multifunctional enzymes for functional characterization and discovery based on the premise that linked enzyme domains have evolved to function collaboratively. Guided by CO-ED, we targeted an unannotated predicted ThiF-nitroreductase di-domain enzyme found in more than 50 proteobacteria. Through heterologous expression and biochemical reconstitution, we discovered a series of natural products containing the rare oxazolone heterocycle and characterized their biosynthesis. Notably, we identified the di-domain enzyme as an oxazolone synthetase, validating CO-ED-guided genome mining as a methodology with potential broad utility for both the discovery of unusual enzymatic transformations and the functional annotation of multidomain enzymes.

Medical Financial Hardship in Survivors of Adolescent and Young Adult Cancer in the United States.

Cancer and its treatment can result in lifelong medical financial hardship, which we aimed to describe among adult survivors of adolescent and young adult (AYA) cancers in the United States. We identified adult (aged ≥18 years) survivors of AYA cancers (diagnosed ages 15-39 years) and adults without a cancer history from the 2010-2018 National Health Interview Surveys. Proportions of respondents reporting measures in different hardship domains (material [eg, problems paying bills], psychological [eg, distress], and behavioral [eg, forgoing care due to cost]) were compared between groups using multivariable logistic regression models and hardship intensity (cooccurrence of hardship domains) using ordinal logistic regression. Cost-related changes in prescription medication use were assessed separately. A total of 2588 AYA cancer survivors (median = 31 [interquartile range = 26-35] years at diagnosis; 75.0% more than 6 years and 50.0% more than 16 years since diagnosis) and 256 964 adults without a cancer history were identified. Survivors were more likely to report at least 1 hardship measure in material (36.7% vs 27.7%, P < .001) and behavioral (28.4% vs 21.2%, P < .001) domains, hardship in all 3 domains (13.1% vs 8.7%, P < .001), and at least 1 cost-related prescription medication nonadherence (13.7% vs 10.3%, P = .001) behavior. Adult survivors of AYA cancers are more likely to experience medical financial hardship across multiple domains compared with adults without a cancer history. Health-care providers must recognize this inequity and its impact on survivors' health, and multifaceted interventions are necessary to address underlying causes.

Operative Intervention Does Not Change Pain Perception in Diabetic Foot Ulcer Patients

Category:Diabetes, Midfoot/ForefootIntroduction/Purpose:Most diabetic foot ulcer (DFU) patients have peripheral neuropathy (PN), which presents with numbness, pain and weakness. DFU patient’s perceived pain and other clinical factors affecting their pain level have not been reported. Although high prevalence of depression among diabetes patients have been reported, its correlation with perception of pain has not been investigated in patients with ulcers. PROMIS (Patient-Reported Outcomes Measurement Information System) allows accurate quantification of patient’s physical function (PF), pain interference (PI) and Depression. We aimed to investigate 1) if DFU patient’s pre- and postoperative pain level correlate with demographic data/ laboratory values/surgical procedure and 2) if depression level and/or surgical intervention impacts pain.Methods:Prospectively collected PROMIS (PF, PI, D) assessments were obtained for patients who underwent surgical intervention for infected DFU between February 2015 and November 2018 (n=240). Patients who had at least 3 consecutive visits with a minimum follow up of 3 months and had completed all assessments for each visit were included (n=92). Demographic data, BMI, medical comorbidities, Hemoglobin A1C (A1C), procedure performed, wound healing status, PN, depression, and amputation level were collected. The mean follow-up duration was 4.7 (3-12) months. T-score distribution of initial PROMIS scores were calculated and compared to the US population. Chi-Square test and Minimum clinically important differences (MCID) were calculated to assess the co-occurrence of different PROMIS domains. We also analyzed other clinical factors and their influences on MCID changes in PROMIS domains.Results:The 92 patients were 80.4% male (n=74) and had an average age of 60.5 (33-96) and BMI of 34.1 (22.0-57.5). Irrigation and debridement (n=39), forefoot amputations (n=46), mid/hindfoot amputations (n=14) and Syme or above amputations (n=12) were performed. Mean pre-operative PF, PI, and depression PROMIS scores were 34.4, 58.7, and 51.4, respectively. Average scores at final follow up increased 1.7, decreased 0.1, and increased 0.2, respectively. Depression and PI were the most strongly associated co-occurrences (p=0.03) pre-operatively and remained significant (p<0.01) with respect to post-operative MCID. PF and PI also strongly co-occurred pre-operatively (p=0.04) and with post-operative MCID assessment (p=0.02). PF was affected by initial A1C (p=0.03) and wound healing status (p=0.03). PN was the only clinical factor found to affect PI (p=0.03).Conclusion:DFU patients with PN experience a significant amount of pain. Contrary to previous studies, we did not find a higher prevalence of depression in our DFU cohort compared to the average United States population. The study results do not indicate the origin of pain, which can be further investigated using other measures, such as PROMIS Neuropathic Pain Quality Scale. Surgical intervention did not significantly relieve pain in DFU patients. These findings may be referenced for pre-operative patient education and setting expectation for surgery.

Childhood physical abuse and emotional neglect are specifically associated with adult mental disorders

Background: Childhood adversities and trauma (CAT) are associated with adult mental disorders. Nevertheless, although CAT of different domains mostly co-occurs, and co-morbidity is common, the associations between CAT and mental disorders, when taking these interrelations into account, are not well known.Aims: We aimed to study differential associations between the five core domains of CAT and current axis-I disorders, taking into consideration their interrelations.Methods: Four hundred and fifteen outpatients attending adult primary (n = 255) and psychiatric care (n = 160) were assessed with the Trauma and Distress Scale (TADS) and the Mini International Neuropsychiatric Interview (MINI). Associations between CAT core domains and diagnostic categories were examined by path analyses.Results: At least some infrequent experience of CAT (83.6%), mostly of neglect, and current mental disorders (49.4%), mostly depression, was frequent, as were co-morbidities and co-occurrence of CAT domains. Considering these interrelations in a path model of excellent fit, physical abuse predicted depressive, manic, psychotic and anxiety disorders, whereas emotional neglect predicted depressive, anxiety and substance misuse disorders.Conclusions: Of all five CAT core domains, physical abuse and emotional neglect had the strongest association with adult psychiatric disorders and might have transmitted earlier reported main effects of other CAT domains onto mental disorders.

A TALE-inspired computational screen for proteins that contain approximate tandem repeats.

TAL (transcription activator-like) effectors (TALEs) are bacterial proteins that are secreted from bacteria to plant cells to act as transcriptional activators. TALEs and related proteins (RipTALs, BurrH, MOrTL1 and MOrTL2) contain approximate tandem repeats that differ in conserved positions that define specificity. Using PERL, we screened ~47 million protein sequences for TALE-like architecture characterized by approximate tandem repeats (between 30 and 43 amino acids in length) and sequence variability in conserved positions, without requiring sequence similarity to TALEs. Candidate proteins were scored according to their propensity for nuclear localization, secondary structure, repeat sequence complexity, as well as covariation and predicted structural proximity of variable residues. Biological context was tentatively inferred from co-occurrence of other domains and interactome predictions. Approximate repeats with TALE-like features that merit experimental characterization were found in a protein of chestnut blight fungus, a eukaryotic plant pathogen.

Weighted mutual information analysis substantially improves domain-based functional network models.

Motivation: Functional protein–protein interaction (PPI) networks elucidate molecular pathways underlying complex phenotypes, including those of human diseases. Extrapolation of domain–domain interactions (DDIs) from known PPIs is a major domain-based method for inferring functional PPI networks. However, the protein domain is a functional unit of the protein. Therefore, we should be able to effectively infer functional interactions between proteins based on the co-occurrence of domains.Results: Here, we present a method for inferring accurate functional PPIs based on the similarity of domain composition between proteins by weighted mutual information (MI) that assigned different weights to the domains based on their genome-wide frequencies. Weighted MI outperforms other domain-based network inference methods and is highly predictive for pathways as well as phenotypes. A genome-scale human functional network determined by our method reveals numerous communities that are significantly associated with known pathways and diseases. Domain-based functional networks may, therefore, have potential applications in mapping domain-to-pathway or domain-to-phenotype associations.Availability and Implementation: Source code for calculating weighted mutual information based on the domain profile matrix is available from www.netbiolab.org/w/WMI.Contact: Insuklee@yonsei.ac.krSupplementary information: Supplementary data are available at Bioinformatics online.

Assessing the co-occurrence of intimate partner violence domains across the life-course: relating typologies to mental health

BackgroundThe inter-generational transmission of violence (ITV) hypothesis and polyvictimisation have been studied extensively. The extant evidence suggests that individuals from violent families are at increased risk of subsequent intimate partner violence (IPV) and that a proportion of individuals experience victimisation across multiple rather than single IPV domains. Both ITV and polyvictimisation are shown to increase the risk of psychiatric morbidity, alcohol use, and anger expression.ObjectiveThe current study aimed to 1) ascertain if underlying typologies of victimisation across the life-course and over multiple victimisation domains were present and 2) ascertain if groupings differed on mean scores of posttraumatic stress disorder (PTSD), depression, alcohol use, and anger expression.MethodUniversity students (N=318) were queried in relation to victimisation experiences and psychological well-being. Responses across multiple domains of IPV spanning the life-course were used in a latent profile analysis. ANOVA was subsequently used to determine if profiles differed in their mean scores on PTSD, depression, alcohol use, and anger expression.ResultsThree distinct profiles were identified; one of which comprised individuals who experienced “life-course polyvictimisation,” another showing individuals who experienced “witnessing parental victimisation,” and one which experienced “psychological victimisation only.” Life-course polyvictims scored the highest across most assessed measures.ConclusionWitnessing severe physical aggression and injury in parental relationships as a child has an interesting impact on the ITV into adolescence and adulthood. Life-course polyvictims are shown to experience increased levels of psychiatric morbidity and issues with alcohol misuse and anger expression.

The Archaeology of Mind

The Archaeology of Mind

O2‐13‐06: Symptom profiles in relation to dementia staging

Most novel treatments for Alzheimer's disease (AD) are likely to be disease-modifying without being curative. In consequence, understanding whether modified disease expression is clinically meaningful is essential. Understanding characteristic profiles can help guide decisions about clinical meaningfulness. Our goal was to characterize profiles of clinically meaningful symptoms in relation to dementia stage. Patients attending a tertiary care Memory Clinic and their care partners were asked to target 4-6 symptoms for treatment. Clinical diagnoses were made using standardized criteria and staging using the Global Deterioration Scale (GDS). Symptoms were defined using the 60-item SymptomGuideTM and grouped by domain (cognition, executive functions, daily function, and behaviour). Patterns of connections between symptoms were assessed using connectivity graphs based on point-wise mutual information, with confidence intervals estimated by bootstrapping. Of 385 patients, 105 met criteria for Mild Cognitive Impairment (MCI) and 269 for AD, of whom 237 were moderate and 32 were severe. Co-occurrence of symptom domains were found to show distinctive trends in symptom profile compositions. Progressing from MCI (GDS = 4) to Moderate (GDS = 5) to Severe (GDS = 6-7), it can been seen that symptomatic profile composition tends to consist of an increased concentration of Daily Function, Cognitive and Executive dysfunctions symptoms (chi-square, p<0.001). Neither Physical Manifestation nor Behavioural symptoms were found to significantly change in frequency as dementia severity increased (chi-square, P = 0.65). While disease-modifying treatments could simply slow typical dementia expression in AD, they also might alter patterns of disease expression. These data suggest that altering the impact on executive and daily function, and on cognition in relation to these domains is most likely to be both clinically meaningful and easy to detect.

Evolution and Quantitative Comparison of Genome-Wide Protein Domain Distributions

The metabolic and regulatory capabilities of an organism are implicit in its protein content. This is often hard to estimate, however, due to ascertainment biases inherent in the available genome annotations. Its complement of recognizable functional protein domains and their combinations convey essentially the same information and at the same time are much more readily accessible, although protein domain models trained for one phylogenetic group frequently fail on distantly related sequences. Pooling related domain models based on their GO-annotation in combination with de novo gene prediction methods provides estimates that seem to be less affected by phylogenetic biases. We show here for 18 diverse representatives from all eukaryotic kingdoms that a pooled analysis of the tendencies for co-occurrence or avoidance of protein domains is indeed feasible. This type of analysis can reveal general large-scale patterns in the domain co-occurrence and helps to identify lineage-specific variations in the evolution of protein domains. Somewhat surprisingly, we do not find strong ubiquitous patterns governing the evolutionary behavior of specific functional classes. Instead, there are strong variations between the major groups of Eukaryotes, pointing at systematic differences in their evolutionary constraints.

Intrinsically disordered domains deviate significantly from random sequences in mammalian proteins

BackgroundIn order to characterize mammalian intrinsically disordered domains (IDDs) we examined the patterns in their amino acid abundance as well as overrepresented local sequence motifs. We considered IDDs from mouse proteins associated with innate immune responses as well as a set of generic human genes. These sets were compared with artificially generated random sequences with the same overall amino acid abundance and length distributions. IDDs were then clustered by amino acid abundance, and further analyzed in terms of co-occurrence of clusters with functionally characterized Pfam domains.ResultsOverall, IDDs were very different from randomly generated sequences. The deviation from random distributions was at least as great as that for ordered domains, for which the deviation can be rationalized in terms of strong evolutionary pressure for structure and function. The co-occurrence of certain Pfam domains with specific IDD clusters was found to be significant (p-value < 0.01). Local sequence motifs that were over-represented in the innate immune set consisted mostly of low complexity fragments, primarily characterized by amino acid repeats, and could not be assigned an obvious functional role.ConclusionsOur results suggest that IDDs are constrained within a narrow subset of possible sequences. This is most likely a result of biophysical restraints that have yet to be elucidated. More detailed examination of the functional relationship between the IDDs and associated Pfam domains is one possible avenue of investigation.

Protein domain organisation: adding order

BackgroundDomains are the building blocks of proteins. During evolution, they have been duplicated, fused and recombined, to produce proteins with novel structures and functions. Structural and genome-scale studies have shown that pairs or groups of domains observed together in a protein are almost always found in only one N to C terminal order and are the result of a single recombination event that has been propagated by duplication of the multi-domain unit.Previous studies of domain organisation have used graph theory to represent the co-occurrence of domains within proteins. We build on this approach by adding directionality to the graphs and connecting nodes based on their relative order in the protein. Most of the time, the linear order of domains is conserved. However, using the directed graph representation we have identified non-linear features of domain organization that are over-represented in genomes. Recognising these patterns and unravelling how they have arisen may allow us to understand the functional relationships between domains and understand how the protein repertoire has evolved.ResultsWe identify groups of domains that are not linearly conserved, but instead have been shuffled during evolution so that they occur in multiple different orders. We consider 192 genomes across all three kingdoms of life and use domain and protein annotation to understand their functional significance.To identify these features and assess their statistical significance, we represent the linear order of domains in proteins as a directed graph and apply graph theoretical methods. We describe two higher-order patterns of domain organisation: clusters and bi-directionally associated domain pairs and explore their functional importance and phylogenetic conservation.ConclusionTaking into account the order of domains, we have derived a novel picture of global protein organization. We found that all genomes have a higher than expected degree of clustering and more domain pairs in forward and reverse orientation in different proteins relative to random graphs with identical degree distributions. While these features were statistically over-represented, they are still fairly rare. Looking in detail at the proteins involved, we found strong functional relationships within each cluster. In addition, the domains tended to be involved in protein-protein interaction and are able to function as independent structural units. A particularly striking example was the human Jak-STAT signalling pathway which makes use of a set of domains in a range of orders and orientations to provide nuanced signaling functionality. This illustrated the importance of functional and structural constraints (or lack thereof) on domain organisation.

Identification and correction of abnormal, incomplete and mispredicted proteins in public databases

BackgroundDespite significant improvements in computational annotation of genomes, sequences of abnormal, incomplete or incorrectly predicted genes and proteins remain abundant in public databases. Since the majority of incomplete, abnormal or mispredicted entries are not annotated as such, these errors seriously affect the reliability of these databases. Here we describe the MisPred approach that may provide an efficient means for the quality control of databases. The current version of the MisPred approach uses five distinct routines for identifying abnormal, incomplete or mispredicted entries based on the principle that a sequence is likely to be incorrect if some of its features conflict with our current knowledge about protein-coding genes and proteins: (i) conflict between the predicted subcellular localization of proteins and the absence of the corresponding sequence signals; (ii) presence of extracellular and cytoplasmic domains and the absence of transmembrane segments; (iii) co-occurrence of extracellular and nuclear domains; (iv) violation of domain integrity; (v) chimeras encoded by two or more genes located on different chromosomes.ResultsAnalyses of predicted EnsEMBL protein sequences of nine deuterostome (Homo sapiens, Mus musculus, Rattus norvegicus, Monodelphis domestica, Gallus gallus, Xenopus tropicalis, Fugu rubripes, Danio rerio and Ciona intestinalis) and two protostome species (Caenorhabditis elegans and Drosophila melanogaster) have revealed that the absence of expected signal peptides and violation of domain integrity account for the majority of mispredictions. Analyses of sequences predicted by NCBI's GNOMON annotation pipeline show that the rates of mispredictions are comparable to those of EnsEMBL. Interestingly, even the manually curated UniProtKB/Swiss-Prot dataset is contaminated with mispredicted or abnormal proteins, although to a much lesser extent than UniProtKB/TrEMBL or the EnsEMBL or GNOMON-predicted entries.ConclusionMisPred works efficiently in identifying errors in predictions generated by the most reliable gene prediction tools such as the EnsEMBL and NCBI's GNOMON pipelines and also guides the correction of errors. We suggest that application of the MisPred approach will significantly improve the quality of gene predictions and the associated databases.

Probabilistic prediction and ranking of human protein-protein interactions

BackgroundAlthough the prediction of protein-protein interactions has been extensively investigated for yeast, few such datasets exist for the far larger proteome in human. Furthermore, it has recently been estimated that the overall average false positive rate of available computational and high-throughput experimental interaction datasets is as high as 90%.ResultsThe prediction of human protein-protein interactions was investigated by combining orthogonal protein features within a probabilistic framework. The features include co-expression, orthology to known interacting proteins and the full-Bayesian combination of subcellular localization, co-occurrence of domains and post-translational modifications. A novel scoring function for local network topology was also investigated. This topology feature greatly enhanced the predictions and together with the full-Bayes combined features, made the largest contribution to the predictions. Using a conservative threshold, our most accurate predictor identifies 37606 human interactions, 32892 (80%) of which are not present in other publicly available large human interaction datasets, thus substantially increasing the coverage of the human interaction map. A subset of the 32892 novel predicted interactions have been independently validated. Comparison of the prediction dataset to other available human interaction datasets estimates the false positive rate of the new method to be below 80% which is competitive with other methods. Since the new method scores and ranks all human protein pairs, smaller subsets of higher quality can be generated thus leading to even lower false positive prediction rates.ConclusionThe set of interactions predicted in this work increases the coverage of the human interaction map and will help determine the highest confidence human interactions.

From sequences to a functional unit

Functional insights at the gene product level would help the drug discovery industry to effectively tap targets for therapeutics and biomedical applications. A complete functional unit can be multidomain, and it is the co-occurrence and interaction of these multiple domains that determine the function and functional diversity of their gene products. With at least 10% of genes from complete genomes existing in fused form, identifying gene fusion events helps us categorize the protein universe into distinct functional units with only sequence information.

Evolutionary cores of domain co-occurrence networks

BackgroundThe modeling of complex systems, as disparate as the World Wide Web and the cellular metabolism, as networks has recently uncovered a set of generic organizing principles: Most of these systems are scale-free while at the same time modular, resulting in a hierarchical architecture. The structure of the protein domain network, where individual domains correspond to nodes and their co-occurrences in a protein are interpreted as links, also falls into this category, suggesting that domains involved in the maintenance of increasingly developed, multicellular organisms accumulate links. Here, we take the next step by studying link based properties of the protein domain co-occurrence networks of the eukaryotes S. cerevisiae, C. elegans, D. melanogaster, M. musculus and H. sapiens.ResultsWe construct the protein domain co-occurrence networks from the PFAM database and analyze them by applying a k-core decomposition method that isolates the globally central (highly connected domains in the central cores) from the locally central (highly connected domains in the peripheral cores) protein domains through an iterative peeling process. Furthermore, we compare the subnetworks thus obtained to the physical domain interaction network of S. cerevisiae. We find that the innermost cores of the domain co-occurrence networks gradually grow with increasing degree of evolutionary development in going from single cellular to multicellular eukaryotes. The comparison of the cores across all the organisms under consideration uncovers patterns of domain combinations that are predominately involved in protein functions such as cell-cell contacts and signal transduction. Analyzing a weighted interaction network of PFAM domains of Yeast, we find that domains having only a few partners frequently interact with these, while the converse is true for domains with a multitude of partners. Combining domain co-occurrence and interaction information, we observe that the co-occurrence of domains in the innermost cores (globally central domains) strongly coincides with physical interaction. The comparison of the multicellular eukaryotic domain co-occurrence networks with the single celled of S. cerevisiae (the overlap network) uncovers small, connected network patterns.ConclusionWe hypothesize that these patterns, consisting of the domains and links preserved through evolution, may constitute nucleation kernels for the evolutionary increase in proteome complexity. Combining co-occurrence and physical interaction data we argue that the driving force behind domain fusions is a collective effect caused by the number of interactions and not the individual interaction frequency.

Issues in predicting protein function from sequence.

Identifying homologues, defined as genes that arose from a common evolutionary ancestor, is often a relatively straightforward task, thanks to recent advances made in estimating the statistical significance of sequence similarities found from database searches. The extent by which homologues possess similarities in function, however, is less amenable to statistical analysis. Consequently, predicting function by homology is a qualitative, rather than quantitative, process and requires particular care to be taken. This review focuses on the various approaches that have been developed to predict function from the scale of the atom to that of the organism. Similarities in homologues' functions differ considerably at each of these different scales and also vary for different domain families. It is argued that due attention should be paid to all available clues to function, including orthologue identification, conservation of particular residue types, and the co-occurrence of domains in proteins. Pitfalls in database searching methods arising from amino acid compositional bias and database size effects are also discussed.

Rotation of biotite porphyroblasts in pelitic schist from the Nukata area, central Japan

The detailed microstructures of biotite porphyroblasts in pelitic schist from the Nukata area, central Japan, indicate that the porphyroblasts rotated in an external reference frame during non-coaxial deformation. The amount of rotation and rotation axis are controlled by the (001) orientation of the biotite porphyroblast with respect to the schistosity and the lineation. Concurrently with rotation, the biotite porphyroblasts suffered shape change by solution and deposition in the shortening and dilating fields around the porphyroblast, respectively. The close co-occurrence of inclusion-free domains (newly deposited biotite domains) and pressure shadows along the (001) faces suggests that continuously opening fractures along the (001) faces caused biotite deposition as well as pressure shadow aggregates. The role of pressure shadow formation for porphyroblast rotation is discussed in terms of stresses applied on the porphyroblast surface. It is concluded that although the formation of ‘deformation-partitioning-induced pressure shadows’ tends to suppress porphyroblast rotation, that of ‘fracture-induced pressure shadows’ (‘pressure fringes’) promotes porphyroblast rotation. The present biotite porphyroblasts would have rotated at rates depending not only on their shape and shape orientation, but also on the (001) orientation.