Table 1 Nonsynonymous changes identified by whole-genome sequencing.

From: Comparative chemical genomics reveal that the spiroindolone antimalarial KAE609 (Cipargamin) is a P-type ATPase inhibitor

Selection

Gene Name

Nucl. change

AA Change

Description

Lineage 1

PMA1

Cca/Aca

P339T

Plasma membrane P2-type H+ -ATPase

Lineage 1

YOS9

aaC/aaA

N490K

ER quality-control lectin

Lineage 1

YRR1

ttG/ttC

L611F

Zn2-Cys6 zinc-finger transcription factor

Lineage 2

PMA1

aaC/aaG

N290S

Plasma membrane P2-type H+-ATPase

Lineage 2

SLA1

Aat/Gat

N788D

Cytoskeletal protein binding protein

Lineage 2

YRR1

aCg/aAg

T623K

Zn2-Cys6 zinc-finger transcription factor

Lineage 3

GCD1

Gtt/Ctt

V450L

Gamma subunit of the translation init. factor eIF2B;

Lineage 3

PMA1

Ggt/Agt

G294S

Plasma membrane P2-type H+-ATPase

  1. Clones were sequenced to 40–90X coverage using paired-end reads and aligned to the S288c reference genome. PMA1 mutations are shown in bold. No intergenic mutations near PMA1 were identified. In addition, PCR analysis of nonclonal cultures identified an additional L291K PMA1 substitution in Lineage 2, Round 5, derived from a parent containing the YRR1 L611F mutation. This genotype was confirmed by whole-genome sequencing. Nonsynonymous coding changes in retrotransposons and flocculation genes (FLO1, FLO4, FLO2, FLO9) were also observed but were considered nonspecific.