Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Antimicrobial Agents and Chemotherapy
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
Epidemiology and Surveillance

Evolution and Genetic Diversity of the k13 Gene Associated with Artemisinin Delayed Parasite Clearance in Plasmodium falciparum

M. Andreína Pacheco, Esha R. Kadakia, Zainab Chaudhary, Douglas J. Perkins, Julia Kelley, Shashidhar Ravishankar, Michael Cranfield, Eldin Talundzic, Venkatachalam Udhayakumar, Ananias A. Escalante
M. Andreína Pacheco
aDepartment of Biology/Institute for Genomics and Evolutionary Medicine (iGEM), Temple University, Philadelphia, Pennsylvania, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Esha R. Kadakia
aDepartment of Biology/Institute for Genomics and Evolutionary Medicine (iGEM), Temple University, Philadelphia, Pennsylvania, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zainab Chaudhary
aDepartment of Biology/Institute for Genomics and Evolutionary Medicine (iGEM), Temple University, Philadelphia, Pennsylvania, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Douglas J. Perkins
bCenter for Global Health, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Julia Kelley
cAtlanta Research and Education Foundation, VAMC, Atlanta, Georgia, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shashidhar Ravishankar
dSchool of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Cranfield
eGorilla Doctors, Wildlife Health Department, University of California, Davis, Davis, California, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eldin Talundzic
fMalaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Venkatachalam Udhayakumar
fMalaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ananias A. Escalante
aDepartment of Biology/Institute for Genomics and Evolutionary Medicine (iGEM), Temple University, Philadelphia, Pennsylvania, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1128/AAC.02550-18
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Article Figures & Data

Figures

  • Tables
  • Additional Files
  • FIG 1
    • Open in new tab
    • Download powerpoint
    FIG 1

    Alignment of the Plasmodium K13 kelch propeller domain. The Pfk13 mutations that have been associated with clinical delayed parasite clearance (2) are shown. The five mutations validated in vivo and in vitro are indicated with an asterisk. The Haemoproteus tartakovskyi (an avian haemosporidian parasite) k13 gene was included as an outgroup.

  • FIG 2
    • Open in new tab
    • Download powerpoint
    FIG 2

    Bayesian phylogenetic hypothesis of Plasmodium parasites based on the k13 gene (42 sequences; 1,985 bp, excluding gaps). The values at the nodes are posterior probabilities (see Materials and Methods). Haemoproteus tartakovskyi (an avian haemosporidian parasite) k13 gene was included as an outgroup.

  • FIG 3
    • Open in new tab
    • Download powerpoint
    FIG 3

    Relative evolutionary rates of the Plasmodium k13 gene. Branches are colored from high (green) to low (purple) according to their relative rates with respect to the rate at the root, which was set to 1, as estimated by RelTime without calibration constraints.

  • FIG 4
    • Open in new tab
    • Download powerpoint
    FIG 4

    Median-joining network of the P. falciparum k13 haplotypes. (A) Median-joining network of the P. falciparum k13 haplotypes using 982 cosmopolitan complete sequences. All the k13 gene sequences obtained here for P. falciparum population samples (n = 463), as well as those available in the PlasmoDB and NCBI databases (n = 519), were included. Branch lengths are proportional to divergence; node sizes are proportional to the total haplotype frequencies. The network shows 147 haplotypes found in 982 sequences with a haplotype diversity (Hd) of 0.742 (SD = 0.012). Every color corresponds to a different geographic origin. Lines separating haplotypes represent mutational steps. The four most frequent haplotypes are indicated. (B) Frequencies of candidate/validated mutations in the propeller domain of the Pfk13 gene that have been associated with clinical delayed parasite clearance by country (Table 2). Frequencies were estimated using an alignment constructed with 3,916 partial (n = 2,934) and complete (n = 982) k13 gene sequences. C-M, China-Myanmar.

Tables

  • Figures
  • Additional Files
  • TABLE 1

    Polymorphism found in k13 gene of Plasmodium falciparum

    Continentπ (SE)dSdNdN − dS (SEa)P value (Z-statistic),b hypothesis testing resultSTajima’s D (P value)No. of haplotypes (Hd)
    Asia (n = 321)0.0004 (0.0002)5.77E−050.00050.0004 (0.0002)0.021 (2.338), dN > dS32−2.268 (<0.01)30 (0.663)
    Africa (n = 411)0.0006 (0.0003)0.00040.00050.0002 (0.0003)0.552 (0.597), dN = dS85−2.654 (<0.001)86 (0.747)
    Americas (n = 128)0.0003 (0.0002)0.00060.0002−0.0004 (0.0003)0.271 (−1.107), dN = dS19−2.306 (<0.01)16 (0.469)
    Total (n = 982)0.0005 (0.0002)0.00030.0006−0.0003 (0.0003)0.317 (1.006), dN = dS146−2.676 (<0.001)147 (0.742)
    • ↵a Standard error (SE) estimates are from 1,000 bootstrap replicates.

    • ↵b P values from the codon-based Z-test are shown. Significant values (P < 0.05) are in bold.

  • TABLE 2

    Number of Pfk13 sequences with mutations (candidates/validated) associated with clinical delayed parasite clearance (per codon and per country)a

    CountryNo. of CDSNo. of sequences inside propeller domain (codons 440 to 680) with:
    Compl.PartialTotalP441LF446IG449AN458YY493HN537DG538VR539TI543TP553LR561HV568GP574LC580YA675V
    Kenya14405419000000000014000
    Mali23213236020000000000000
    Nigeria292756000000000000001
    Cambodia257000000000000020
    China0329329011901000005101620
    China-Myanmar border570570280100010000300
    India0140140000000000010000
    Myanmar04343101100110210131
    Thailand2609731,23381210119061400210632980
    Papua New Guinea077000000000000010
    Total3852,1422,527916111149071607254833062
    • ↵a The total number of complete (Compl.) and partial sequences obtained from the databases (PlasmoDB and NCBI) are shown. CDS, coding sequences.

Additional Files

  • Figures
  • Tables
  • Supplemental material

    • Supplemental file 1 -

      Supplemental Data Sets S1 to S6

      XLSX, 1.1M

PreviousNext
Back to top
Download PDF
Citation Tools
Evolution and Genetic Diversity of the k13 Gene Associated with Artemisinin Delayed Parasite Clearance in Plasmodium falciparum
M. Andreína Pacheco, Esha R. Kadakia, Zainab Chaudhary, Douglas J. Perkins, Julia Kelley, Shashidhar Ravishankar, Michael Cranfield, Eldin Talundzic, Venkatachalam Udhayakumar, Ananias A. Escalante
Antimicrobial Agents and Chemotherapy Jul 2019, 63 (8) e02550-18; DOI: 10.1128/AAC.02550-18

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Antimicrobial Agents and Chemotherapy article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Evolution and Genetic Diversity of the k13 Gene Associated with Artemisinin Delayed Parasite Clearance in Plasmodium falciparum
(Your Name) has forwarded a page to you from Antimicrobial Agents and Chemotherapy
(Your Name) thought you would be interested in this article in Antimicrobial Agents and Chemotherapy.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Evolution and Genetic Diversity of the k13 Gene Associated with Artemisinin Delayed Parasite Clearance in Plasmodium falciparum
M. Andreína Pacheco, Esha R. Kadakia, Zainab Chaudhary, Douglas J. Perkins, Julia Kelley, Shashidhar Ravishankar, Michael Cranfield, Eldin Talundzic, Venkatachalam Udhayakumar, Ananias A. Escalante
Antimicrobial Agents and Chemotherapy Jul 2019, 63 (8) e02550-18; DOI: 10.1128/AAC.02550-18
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ABSTRACT
    • INTRODUCTION
    • RESULTS
    • DISCUSSION
    • MATERIALS AND METHODS
    • ACKNOWLEDGMENTS
    • FOOTNOTES
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

Plasmodium falciparum
Plasmodium vivax
artemisinin resistance
k13 gene
kelch propeller domain
rates of evolution

Related Articles

Cited By...

About

  • About AAC
  • Editor in Chief
  • Editorial Board
  • Policies
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • AAC Podcast
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Article Types
  • Ethics
  • Contact Us

Follow #AACJournal

@ASMicrobiology

       

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 0066-4804; Online ISSN: 1098-6596