Fine-Scale Haplotype Structure Reveals Strong Signatures of Positive Selection in a Recombining Bacterial Pathogen

Mol Biol Evol. 2020 Feb 1;37(2):417-428. doi: 10.1093/molbev/msz225.

Abstract

Identifying genetic variation in bacteria that has been shaped by ecological differences remains an important challenge. For recombining bacteria, the sign and strength of linkage provide a unique lens into ongoing selection. We show that derived alleles <300 bp apart in Neisseria gonorrhoeae exhibit more coupling linkage than repulsion linkage, a pattern that cannot be explained by limited recombination or neutrality as these couplings are significantly stronger for nonsynonymous alleles than synonymous alleles. This general pattern is driven by a small fraction of highly diverse genes, many of which exhibit evidence of interspecies horizontal gene transfer and an excess of intermediate frequency alleles. Extensive simulations show that two distinct forms of positive selection can create these patterns of genetic variation: directional selection on horizontally transferred alleles or balancing selection that maintains distinct haplotypes in the presence of recombination. Our results establish a framework for identifying patterns of selection in fine-scale haplotype structure that indicate specific ecological processes in species that recombine with distantly related lineages or possess coexisting adaptive haplotypes.

Keywords: adaptation; computational biology; evolutionary genetics; linkage; microbiology; simulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't