Segregation lag in polyploid cells of the pathogen genus Borrelia: Implications for antigenic variation: Implications for antigenic variation

Christopher D. Crowder, Richard Lane Denny, Alan G. Barbour

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Relapsing fever agents like Borrelia hermsii undergo multiphasic antigenic variation that is attributable to spontaneous DNA non-reciprocal transpositions at a particular locus in the genome. This genetic switch results in a new protein being expressed on the cell surface, allowing cells with that phenotype to escape prevailing immunity. But the switch occurs in only one of several genomes in these spirochetes, and a newly-switched gene is effectively “recessive” until homozygosity is achieved. The longer that descendants of the switched cell expressed both old and new proteins, the longer this lineage risks neutralization by antibody to the old protein. We investigated the implications for antigenic variation of the phenotypic lag that polyploidy would confer on cells. We first experimentally determined the average genome copy number in daughter cells after division during mouse infection with B. hermsii strain HS1. We then applied discrete deterministic and stochastic simulations to predict outcomes when genomes were equably segregated either linearly, i.e. according to their position in one-dimensional arrays, or randomly partitioned, as for a sphere. Linear segregation replication provided for a lag in achievement of homozygosity that was significantly shorter than could be achieved under the random segregation condition. For cells with 16 genomes, this would be a 4-generation lag. A model incorporating the immune response and evolved matrices of switch rates indicated a greater fitness for polyploid over monoploid bacteria in terms of duration of infection.

Original languageEnglish (US)
Pages (from-to)195-218
Number of pages24
JournalYale Journal of Biology and Medicine
Volume90
Issue number2
StatePublished - Jun 1 2017

Keywords

  • Lyme disease
  • Plasmid
  • Relapsing fever
  • Spirochete
  • Tick
  • Vector-borne disease

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Segregation lag in polyploid cells of the pathogen genus Borrelia: Implications for antigenic variation: Implications for antigenic variation'. Together they form a unique fingerprint.

Cite this