Open access paper from Genome Biology on genome inversions in bacteria and archaea.
Abstract
BACKGROUND: Whole-genome comparisons can provide great insight into many aspects of biology. Until recently, however, comparisons were mainly possible only between distantly related species. Complete genome sequences are now becoming available from multiple sets of closely related strains or species.
RESULTS: By comparing the recently completed genome sequences of Vibrio cholerae, Streptococcus pneumoniae and Mycobacterium tuberculosis to those of closely related species - Escherichia coli, Streptococcus pyogenes and Mycobacterium leprae, respectively - we have identified an unusual and previously unobserved feature of bacterial genome structure. Scatterplots of the conserved sequences (both DNA and protein) between each pair of species produce a distinct X-shaped pattern, which we call an X-alignment. The key feature of these alignments is that they have symmetry around the replication origin and terminus; that is, the distance of a particular conserved feature (DNA or protein) from the replication origin (or terminus) is conserved between closely related pairs of species. Statistically significant X-alignments are also found within some genomes, indicating that there is symmetry about the replication origin for paralogous features as well.
CONCLUSIONS: The most likely mechanism of generation of X-alignments involves large chromosomal inversions that reverse the genomic sequence symmetrically around the origin of replication. The finding of these X-alignments between many pairs of species suggests that chromosomal inversions around the origin are a common feature of bacterial genome evolution.
despite of the enormous genomic diversity, the phage genome mapping is being done using a plethora of techniques,which includes both genetic mapping and physical mapping
This presentation intends to explore the application of virus in different biomedical fields and research with special reference to vaccine production and plant viral diseases.
This is the first presentation of the BITS training on 'Comparative genomics'.
It reviews the basic concepts of sequence homology on different levels.
Thanks to Klaas Vandepoele of the PSB department.
despite of the enormous genomic diversity, the phage genome mapping is being done using a plethora of techniques,which includes both genetic mapping and physical mapping
This presentation intends to explore the application of virus in different biomedical fields and research with special reference to vaccine production and plant viral diseases.
This is the first presentation of the BITS training on 'Comparative genomics'.
It reviews the basic concepts of sequence homology on different levels.
Thanks to Klaas Vandepoele of the PSB department.
A complete set of chromosomes/genes inherited as a unit from one parent called genome. The entire genetic complement of a living organism.
The total amount of genetic information in the chromosomes of an organism, including its genes and DNA sequences. The genome of eukaryotes is made up of a single, haploid set of chromosomes that is contained in the nucleus of every cell and exists in two copies in the chromosomes of all cells except reproductive and red blood cells. The human genome is made up of about 35,000 genes.
Comparative genomics: Genomic features are compared, evolutionary relationship
The major principle of comparative genomics is that common features of two organisms will often be encoded within the DNA that is evolutionarily conserved between them. orthologous sequences,
Started as soon as the whole genomes of two organisms became available (that is, the genomes of the bacteria Haemophilus influenzae and Mycoplasma genitalium) in 1995, comparative genomics is now a standard component of the analysis of every new genome sequence. comparative genomics studies of small model organisms (for example the model Caenorhabditis elegans and closely related Caenorhabditis briggsae) are of great importance to advance our understanding of general mechanisms of evolution
Computational tools for analyzing sequences and complete genomes. Application of comparative genomics in agriculture and medicine.
Detection of genomic homology in eukaryotic genomesKlaas Vandepoele
i-ADHoRe 3.0--fast and sensitive detection of genomic homology in extremely large data sets.
Proost S, Fostier J, De Witte D, Dhoedt B, Demeester P, Van de Peer Y, Vandepoele K.
Nucleic Acids Res. 2012 Jan;40(2):e11.
Comparative genomics is a powerful means to gain insight into the evolutionary processes that shape the genomes of related species. As the number of sequenced genomes increases, the development of software to perform accurate cross-species analyses becomes indispensable. However, many implementations that have the ability to compare multiple genomes exhibit unfavorable computational and memory requirements, limiting the number of genomes that can be analyzed in one run. Here, we present a software package to unveil genomic homology based on the identification of conservation of gene content and gene order (collinearity), i-ADHoRe 3.0, and its application to eukaryotic genomes. The use of efficient algorithms and support for parallel computing enable the analysis of large-scale data sets. Unlike other tools, i-ADHoRe can process the Ensembl data set, containing 49 species, in 1 h. Furthermore, the profile search is more sensitive to detect degenerate genomic homology than chaining pairwise collinearity information based on transitive homology. From ultra-conserved collinear regions between mammals and birds, by integrating coexpression information and protein-protein interactions, we identified more than 400 regions in the human genome showing significant functional coherence. The different algorithmical improvements ensure that i-ADHoRe 3.0 will remain a powerful tool to study genome evolution.
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Innovations in Sequencing & Bioinformatics
Talk for
Healthy Central Valley Together Research Workshop
Jonathan A. Eisen University of California, Davis
January 31, 2024 linktr.ee/jonathaneisen
Thoughts on UC Davis' COVID Current ActionsJonathan Eisen
Slides I used for a presentation to Chancellor May's leadership council about the current state of UC Davis' response to COVID and how it could be improved
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
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These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
2. 2 Genome Biology Vol 1 No 6 Eisen et al.
Results and discussion at the same distance from the origin but not necessarily on
Whole-genome X-alignments between species at the the same side of the origin. The X-alignment between
DNA level V. cholerae and E. coli was found to be statistically signifi-
We compared the DNA sequences of the two chromosomes cant using a test based on the number of matches found in
of Vibrio cholerae [4] with the sequence of the Escherichia diagonal strips in the alignment (see the Materials and
coli chromosome [5] using a suffix tree alignment algorithm methods section). Specifically, when V. cholerae chrI is
[6]. The analysis revealed a significant alignment at the DNA aligned in the forward direction against E. coli, there are 459
level between the V. cholerae large chromosome (chrI) [4] maximal unique matching subsequences (MUMs; see the
and the E. coli chromosome [5] spanning the entire length of Materials and methods section), of which 177 occurred in a
these chromosomes (Figure 1a). Analysis of the reverse com- diagonal strip covering 10% of the total area (compared to
plement of V. cholerae chrI with E. coli also produced a sig- the expected value of 46). The probability of observing this
nificant alignment (Figure 1b). When superimposed, the two high a number of MUMs by chance is 4.7 x 10–59. The align-
alignments produce a clear ‘X’ shape (Figure 1c) that is sym- ment of V. cholerae chrI in the reverse direction against E. coli
metric about the origin of replication of both genomes. This (which corresponds to the MUMs on the anti-diagonal) has a
symmetry indicates that matching sequences tend to occur probability of 1.8 x 10–90. As a control, we compared the
(a) (b) (c)
5,000,000 5,000,000 5,000,000
4,000,000 4,000,000 4,000,000
3,000,000 3,000,000 3,000,000
E. coli
E. coli
E. coli
2,000,000 2,000,000 2,000,000
1,000,000 1,000,000 1,000,000
0 0 0
0
1,000,000
2,000,000
3,000,000
0
1,000,000
2,000,000
3,000,000
0
1,000,000
2,000,000
3,000,000
V. cholerae chromosome I V. cholerae chromosome I reverse V. cholerae chromosome I
(d) (e)
2,000,000 4,000,000
1,500,000 3,000,000
M. tuberculosis
S. pyogenes
1,000,000 2,000,000
500,000 1,000,000
0 0
0
1,000,000
2,000,000
3,000,000
0
5,000,00
1,000,000
1,500,000
2,000,000
S. pneumoniae M. leprae
Figure 1
Between-species whole-genome DNA alignments. Plots of maximally unique matching subsequences (MUMs) between
genomes as identified by the MUMmer program. (a) V. cholerae chrI forward strand versus E. coli forward strand. (b) E. coli
forward versus V. cholerae chrI reverse. (c) V. cholerae chrI versus E. coli, forward and reverse overlaid. (d) S. pneumoniae
forward versus S. pyogenes forward and reverse overlaid. (e) M. tuberculosis forward versus M. leprae forward and reverse
overlaid. A point ( x,y) indicates a DNA sequence that occurs once within each genome, at location x in one genome and at
location y in the other genome. The matching sequences may occur on either the forward or the reverse strand; in either case,
the locations indicate the 5’ end of the sequences. The point (0,0) corresponds to the origin of replication for each genome.
3. http://genomebiology.com/2000/1/6/research/0011.3
Table 1 species (see the Materials and methods section). Figure 2a
shows a scatterplot of chromosome positions of all proteins
Whole-genome DNA alignments using MUMmer
homologous between V. cholerae chrI and E. coli. The pres-
comment
Organism 1 Organism 2 Total Matches Probability* ence of many large gene families causes a great deal of noise
MUMs within in this comparison. This noise can be reduced by considering
diagonal only the best matching homolog for each open reading frame
(10%)
(ORF), rather than all protein homologs (Figure 2b). This fil-
V. cholerae E. coli 459 177 4.7 x 10-59 tered protein comparison results in an X-alignment that is
statistically significant (Table 2).
V. cholerae (rev) E. coli 467 217 1.8 x 10-90
V. cholerae (rev) V. cholerae 342 86 8.2 x 10-16 Whole-genome X-alignments within species
reviews
E. coli (rev) E. coli 1,128 225 1.5 x 10-23 The finding of the X-alignment pattern between species led
S. pyogenes S. pneumoniae 706 259 4.5 x 10-80 us to search for similar patterns within species; that is, global
alignments of a genome with its own reverse complement. Of
S. pyogenes (rev) S. pneumoniae 626 255 2.3 x 10-90
the genomes for which we found between-species X-align-
S. pyogenes (rev) S. pyogenes 367 96 1.1 x10-18 ments (M. tuberculosis, M. leprae, S. pyogenes, S. pneumo-
S. pneumoniae (rev) S. pneumoniae 1,054 154 1.5 x 10-6 niae, E. coli and V. cholerae), statistically significant
self-alignments are detected for all except M. tuberculosis
M. leprae (rev) M. leprae 449 89 3.5 x 10-10
(Figure 3; probabilities shown in Table 1). Interestingly, these
reports
M. tuberculosis (rev) M. tuberculosis 2,476 268 0.092 self-alignments are not as strong as those between species.
E. coli M. tuberculosis 81 13 0.06 Proteome analysis also shows an X-alignment within species
E. coli (rev) M. tuberculosis 70 5 0.84 (shown for V. cholerae chrI in Figure 2d; probabilities shown
in Table 2). The X-alignment of proteins within V. cholerae
*Statistical significance was estimated as described in the text; rev, chrI is statistically significant only for recently duplicated-
reverse complement sequence. genes, but disappears when all paralogs are included. The
importance of filtering for recent duplications is discussed
deposited research
genomes of distantly related species, such as E. coli and below.
Mycobacterium tuberculosis. These do not show a signifi-
cant X-alignment (Table 1). Model I: whole-genome inverted duplications
One possible explanation for an X-alignment within and
We have found that X-alignments of whole genomes are not between species is an ancestral inverted duplication of the
limited to the V. cholerae versus E. coli comparison. For whole genome, as has been suggested for E. coli [10]. The
example, a whole-genome comparison of two bacteria in the weak or missing X-alignment within species could be
genus Streptococcus - S. pyogenes [7] and S. pneumoniae
refereed research
(H. Tettelin, personal communication) - reveals a global Table 2
X-alignment similar to that of V. cholerae versus E. coli Whole-genome protein-level comparisons
(Figure 1d) which is also statistically significant (Table 1). In
addition, an X-alignment is found between two species in Organism 1 Organism 2 Total Matches Probability*
the genus Mycobacterium - M. tuberculosis [8] and matches within
10%
M. leprae [9] (Figure 1e) - as well as between two strains of
diagonal
Helicobacter pylori (data not shown). The X-alignments
observed between any two pairs of genomes are not identical Top matches
in every aspect. For example, in the alignment between the
interactions
V. cholerae E. coli 1,797 369 3.2 x 10-40
two Mycobacterium species, each conserved region is much
V. cholerae (rev) E. coli 1,797 441 2.3 x 10-70
longer than in the other genome pairs. We believe this is due
to different numbers of evolutionary events between the V. cholerae V. cholerae 701 145 3.6 x 10-17
species (see below). Whole-genome X-alignments were not V. cholerae (rev) V. cholerae 701 70 0.52
found between any other pairs of species, although a related
E. coli E. coli 1,985 286 3.6 x 10-10
pattern was seen between some of the chlamydial species
(see below). E. coli (rev) E. coli 1,985 210 0.20
information
Recent duplications†
Whole-genome X-alignments between species are V. cholerae V. cholerae 195 60 1.0 x 10-15
also found at the proteome level
V. cholerae (rev) V. cholerae 195 26 8.4 x 10-4
To test whether the X-alignments found in the DNA analysis
could also be found at the level of whole proteomes, we con- *Statistical significance was estimated as described in the text. †Best
ducted comparisons of homologous proteins between match to another V. cholerae ORF versus any other complete genome.
4. 4 Genome Biology Vol 1 No 6 Eisen et al.
(a) (b)
4,000,000 4,000,000
3,000,000 3,000,000
E. coli
E. coli
2,000,000 2,000,000
1,000,000 1,000,000
0 0
0
1,000,000
2,000,000
3,000,000
0
1,000,000
2,000,000
3,000,000
V. cholerae V. cholerae
(c) (d) 3,000,000
1,000,000
2,000,000
C. pneumoniae
V. cholerae
T R
500,000
1,000,000
0 0
0
500,000
1,000,000
0
1,000,000
2,000,000
3,000,000
C. trachomatis V. cholerae
Figure 2
Whole-genome proteome alignments. Plots show the chromosome locations of pairs of predicted proteins that have
significant similarity (on the basis of fasta3 comparisons). (a) V. cholerae chrI versus E. coli. All significant matches for each
V. cholerae ORF are shown. (b) V. cholerae chrI versus E. coli, top matches. Only the best match for each V. cholerae ORF is
shown. The filtering for top matches for each ORF removes noise due to the presence of many large multigene families. This
X-alignment is highly statistically significant (Table 2). (c) Chlamydia trachomatis versus C. pneumoniae, top matches. Only the
best match for each C. trachomatis ORF is shown. The position of the origins (R) and termini (T) of replication are slightly
shifted to see the inversions better. This pattern is consistent with the occurrence a small number of inversions around the
origin and terminus in the two lineages since their divergence from a common ancestor (see Figure 4). (d) V. cholerae chrI
versus V. cholerae chrI, self-alignment. Only recently duplicated pairs of genes are shown. Recent duplications were
operationally defined as those genes that were more similar to another gene in V. cholerae than to any gene in any other
complete genome sequence. The faint X-alignment is statistically significant (Table 2). No significant X-alignment was detected
when all pairs of paralogs were included.
explained by gene loss of one of the two duplicates of many between species, the member of the gene pair lost in a par-
of the pairs of genes in the different lineages. Gene loss has ticular lineage should be essentially random. If an ancient
been found to follow large chromosomal or genome duplica- inverted duplication followed by differential gene loss is the
tions [11-13]. This gene loss is thought to stabilize large correct explanation for the observed X-alignments, one
duplications by preventing recombination events between would expect the genes along one diagonal to be orthologous
duplicate genes. If gene loss is responsible for the weak between species (related to each other by the speciation
X-alignment within species, then to maintain the X-alignments event), while the genes along the other diagonal should be
5. http://genomebiology.com/2000/1/6/research/0011.5
(a) 3,000,000 (b)
4,000,000
comment
2,000,000
3,000,000
V. cholerae
E. coli
2,000,000
1,000,000
1,000,000
reviews
0 0
0
1,000,000
2,000,000
3,000,000
0
1,000,000
2,000,000
3,000,000
4,000,000
V. cholerae chromosome I E. coli
(c) 2,000,000
(d)
reports
2,000,000
1,500,000
1,500,000
S. pneumoniae
S. pyogenes
1,000,000
1,000,000
deposited research
500,000 500,000
0 0
0
500,000
1,000,000
1,500,000
2,000,000
0
500,000
1,000,000
1,500,000
2,000,000
refereed research
S. pyogenes S. pneumoniae
Figure 3
Within-genome DNA alignments. Plots of exactly matching sequences within four genomes as identified by the MUMmer
program: (a) V. cholerae; (b) E. coli; (c) S. pyogenes; (d) S. pneumoniae. A point (x,y) indicates a DNA sequence that is
repeated within the genome, occurring once at location x and again at location y. Points near the diagonal (y = x) correspond
to tandem repeats. Points near the anti-diagonal (y = L -x, where L is genome length) correspond to repeats that occur at
symmetric locations about the origin of location. The point (0,0) corresponds to the origin of replication in each plot.
Statistically significant X-alignments occur in all four species (Table 1).
interactions
paralogous (related to each other by the genome duplication possible mechanisms for such movement, but we believe the
event before the speciation of the two lineages). However, most likely explanation is the occurrence of large chromoso-
the evidence appears to contradict this model: likely ortholo- mal inversions that pivot around the replication origin
gous gene pairs are equally distributed on each diagonal and/or terminus. Large chromosomal inversions, including
(data not shown). those that occur around the replication origin and terminus,
have been shown to occur in E. coli and Salmonella
information
Model II: chromosomal inversions about the origin typhimurium in the laboratory (see, for example, [14-18]).
and/or terminus The occurrence of such inversions over evolutionary time
A second possible explanation for the X-alignments is that an scales was first suggested by comparative analysis of the com-
underlying mechanism allows sections of DNA to move plete genomes of four strains in the genus Chlamydia [19]. In
within the genome but maintains the distance of these sec- that study, we found that the major chromosomal differ-
tions from the origin and/or terminus. There are a variety of ences between C. pneumoniae and C. trachomatis (shown in
6. 6 Genome Biology Vol 1 No 6 Eisen et al.
A2 A3
31 32 1 2 31 32 1 2 2 1 32 31
30 3 30 3 3 30
29 4 29 4 4 29
28 5 28 5 5 28
27 6 27 6
A2 *
27 *
6
26 7 A1 26 7 26 7
25
24 A1 8
9
25
24
A2 8
9
25
24 A3 8
9
23 10 23 10 23 10
22 11 22 11 22 11
21
20
12
13 Inversion 21
20
12
13 Inversion 21
20
12
13
19 14 14 19 14 19
18 17 16 15
around * 15 16 17 18 * around 15 16 17 18
terminus (*) origin (*)
32 1 2
30 31 3
29 4
28 5
27 6
26 Common 7
25
24 ancestor of
8
9 B1 B2 B3
23 10
22 A and B 11
21 12
20 13
19 14
18 17 16 15
A1 A2 A3
30 31
32 1 2
3
Inversion 30 31
32 1 2
3
Inversion 3 2
1 32 31
30
29 4 29 4 *
29 4*
28 5 around 28 5 around 28 5
27 6 27 6 27 6
26 7 terminus (*) 26 7 origin (*) 26 7
25 8 * 8 *
25 8 25
24
23
B1 10
9 9
10
B2 24
23
9
10
B3 24
23
22 11 11 22 11 22
21 12 12 21 12 21
20 13 13 20 13 20
19 14 14 19 14 19
18 17 16 15 15 16 17 18 15 16 17 18
B2 B3
B1 B2
Figure 4
Schematic model of genome inversions. The model shows an initial speciation event, followed by a series of inversions in the
different lineages (A and B). Inversions occur between the asterisks (*). Numbers on the chromosome refer to hypothetical
genes 1-32. At time point 1, the genomes of the two species are still co-linear (as indicated in the scatterplot of A1 versus
B1). Between time point 1 and time point 2, each species (A and B) undergoes a large inversion about the terminus (as
indicated in the scatterplots of A1 versus A2 and B1 versus B2). This results in the between-species scatterplot looking as if
there have been two nested inversions (A2 versus B2), similar to that seen for C. trachomatis versus C. pneumoniae (see
Figure 2). Between time point 2 and time point 3 each species undergoes an additional inversion (as indicated in the
scatterplots of B2 versus B3 and A2 versus A3). This results in the between-species scatterplots beginning to resemble an
X-alignment, similar to that seen in M. tuberculosis versus M. leprae (see Figure 2).
Figure 2c) were consistent with the occurrence of large could produce patterns very similar to those seen in the
inversions that pivoted around the origin and terminus Chlamydia, Mycobacterium and Helicobacter comparisons.
(including multiple inversions of different sizes). In Figure 4 The continued occurrence of such inversion over longer time
we present a hypothetical model showing how a small scales would result in an X-alignment similar to that seen in
number of inversions centered around the origin or terminus the V. cholerae versus E. coli and S. pneumoniae versus
7. http://genomebiology.com/2000/1/6/research/0011.7
S. pyogenes comparisons. Thus the different between- within the bacterial chromosome that inverts the sequence
species X-alignments could be the result of different from the origin up to that point. As with inversion events,
numbers of inversions between particular pairs of species. recombination and replication have been found to be tightly
comment
coupled [25].
Inversions about the origin and terminus could also produce
an X-alignment within species, through the splitting of
tandemly duplicated sequence. Many sets of tandemly dupli- Conclusions
cated genes are found in most bacterial genomes [19,20] We present here a novel observation regarding the conserva-
(also see Figure 3a,c). As tandem duplications are inherently tion between bacterial species of the distance of particular
unstable (one of the duplicates can be rapidly eliminated by genes from the replication origin or terminus. The initial
slippage and/or recombination events [21]), the fact that observation was only possible due to the availability of com-
reviews
many tandem pairs are present within each genome suggests plete genome sequences from pairs of moderately closely
that tandem duplications occur frequently. Thus, it is rea- related species (for example, V. cholerae and E. coli). This
sonable to assume that occasionally a large inversion will shows the importance of having genome pairs from many
split a pair of tandemly duplicated genes. An inversion that levels of evolutionary relatedness. Comparisons of distantly
pivots about the origin and also splits a tandem duplication related species enable the determination of universal fea-
will result in a pair of paralogous genes spaced symmetri- tures of life as well as of events that occur very rarely. Com-
cally on opposite sides of the origin. parison of very closely related species allows the
identification of frequent events such as transitional changes
reports
If our inversion model is correct, then the genes along both at third codon positions or tandem duplications. To eluci-
diagonals in the between-species alignments should be date all other events in the history of life, genome pairs cov-
orthologous, which is the case (see above). In contrast, genes ering all the intermediate levels of evolutionary relatedness
along the anti-diagonal in the within-species X-alignments will be needed.
should be recent tandem duplicates that have been sepa-
rated by inversions. This also appears to be the case - in the
within-species analysis of V. cholerae chrI ORFs, the
deposited research
Materials and methods
X-alignment shows up best when only recent duplicates are Genomes analyzed
analyzed (Figure 2d). The splitting of tandem duplicates by Complete published genome sequences were obtained from the
inversions may be a general mechanism to stabilize the coex- National Center for Biotechnology Information website [26] or
istence of duplicated genes, as it will prevent their elimina- from the TIGR Comprehensive Microbial Resource [27]. These
tion by unequal crossing-over or replication slippage events. included Aeropyrum pernix [28], Aquifex aeolicus [29],
Archaeoglobus fulgidus [30], Bacillus subtilis [31], Borrelia
What could cause inversions that pivot around the origin burgdorferi [32], Campylobacter jejuni [33], Chlamydia
and terminus of the genome to occur more frequently than pneumoniae AR39 [19], Chlamydia pneumoniae CWL029
refereed research
other inversions? One possibility is that many inversions [34], Chlamydia trachomatis (D/UW-3/Cx) [35], Chlamydia
occur, but there is selection against those that change the trachomatis MoPn [19], Deinococcus radiodurans [36],
distance of a gene from the origin or terminus. Such a possi- Escherichia coli [5], Haemophilus influenzae [37], Helicobac-
bility has been suggested by experimental work in E. coli ter pylori [38], Helicobacter pylori J99 [39], Methanobac-
[14,15]. Additional studies have, however, suggested that terium thermoautotrophicum [40], Methanococcus jannaschii
there is little selective difference between inversions and that [41], Mycobacterium tuberculosis [8], Mycoplasma genital-
instead there may be certain regions that are more prone to ium [42], Mycoplasma pneumoniae [43], Neisseria meningi-
inversion than others [16-18,22,23]. Alternatively, the inver- tidis MC58 [20], Neisseria meningitidis serogroup A strain
sion events could be linked to replication, as has been sug- Z2491 [44], Pyrococcus horikoshii [45], Rickettsia prowazekii
gested for small local inversion events [24]. Whatever the [46], Synechocystis sp. [47], Thermotoga maritima [48], Tre- interactions
mechanisms, the fact that we find evidence for such inver- ponema pallidum [49], and Vibrio cholerae [4]. In addition, a
sions between many pairs of species suggests that they are a few unpublished genomes were analyzed: Streptococcus pyo-
common feature of bacterial evolution. Many aspects of the genes (obtained from the Oklahoma University Genome Center
X-alignments require further exploration. For example, to website [7]), Streptococcus pneumoniae (H. Tettelin, personal
split a tandem duplication, an inversion must fall precisely communication), and Mycobacterium leprae (obtained from
on the boundary between two duplicated genes. This would the Sanger Centre Pathogen Sequencing Group website [9]).
information
appear to be unlikely, requiring a large number of inversions
in order to generate a sufficient number of split gene pairs. If Whole-genome DNA alignments
the mechanisms of gene duplication are somehow related to DNA alignments of the complete genomic sequences of all
the mechanisms of inversion, however, then this model is bacteria used in this study were accomplished with the
more plausible. The process of duplicating a gene, if it occurs MUMmer program [6]. This program uses an efficient suffix
during replication, might promote a recombination event tree construction algorithm to rapidly compute alignments
8. 8 Genome Biology Vol 1 No 6 Eisen et al.
of entire genomes. The algorithm identifies all exact matches termini of S. pneumoniae and S. pyogenes were determined
of nucleotide subsequences that are contained in both input by the authors of the present study using GC-skew analysis
sequences; these exact matches must be longer than a speci- and the locations of characteristic genes, particularly the
fied minimum length, which was set to 20 base pairs for this chromosome replication initiator gene dnaA.
comparison. To search for genome-scale alignments within
species, complete bacterial and archaeal genomes (25 in
total including all published genomes) were aligned with Acknowledgements
their own reverse complements. To search for between- We thank S. Eddy, M.A. Riley, T. Read, A. Stoltzfus, M-I Benito and I.
Paulsen for helpful comments, suggestions and discussions. S.L.S. was sup-
species alignments, all genomes were aligned against all ported in part by NSF grant IIS-9902923 and NIH grant R01 LM06845. S.L.S.
others in both orientations. and J.A.E were supported in part by NSF grant KDI-9980088. Data for all
published complete genome sequences were obtained from the NCBI
genomes database [26] or from The Institute for Genomic Research (TIGR)
Whole-genome protein comparisons Microbial Genome Database [27]. The sequences of V. cholerae, S. pneumo-
The predicted proteome of each complete genome niae, and M. tuberculosis (CDC 1551) were determined at TIGR with
support from NIH and the NIAID. The M. leprae sequence data were pro-
sequence (all predicted proteins in the genome) was com- duced by the Pathogen Sequencing Group at the Sanger Centre. Sequencing
pared to the proteomes of all complete genome sequences of M. leprae is funded by the Heiser Program for Research in Leprosy and
(including itself) using the fasta3 program [50]. Matches Tuberculosis of The New York Community Trust and by L’Association
Raoul Follereau. The M. tuberculosis CDC 1551 genome sequence was
with an expected score (e-value) of 10–5 or less were con- obtained from TIGR. The source of the S. pyogenes genome sequence was
sidered significant. the Streptococcal Genome Sequencing Project funded by USPHS/NIH grant
AI38406, and was kindly made available by B. A. Roe, S.P. Linn, L. Song, X.
Yuan, S. Clifton, R.E. McLaughlin, M. McShan and J. Ferretti, and can be
Statistical significance of X-alignments obtained from the website of the Oklahoma University Genome Center [7].
To calculate the statistical significance of the X-alignments,
the maximal unique matching subsequences (MUMs) for
unrelated genomes were examined and found to be uni- References
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