Background
Methods
Parasite sample
Amplification and DNA sequencing of the Plasmodium falciparum ldh gene
Retrieval of ldh sequences from human, gorilla, chimpanzee, and simian malaria parasites
Population genetic analysis of the Plasmodium falciparum ldh gene
Phylogenetic analysis
Results
Nucleotide sequences of the ldh gene in Thai Plasmodium falciparum isolates
Allele | Isoform | Nucleotide position (corresponding amino acid position) | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
36 (12) | 73 (25) | 85 (29) | 259 (87) | 399 (133) | 407 (136) | 450 (150) | 451 (151) | 513 (171) | 560 (187) | 563 (188) | 783 (261) | 814 (272) | 858 (286) | 891 (297) | ||
L1a
| LDH-1 | TCA
S
| CAG
Q
| GGA
G
| GGA
G
| GTA
V
| TTA
L
| TTA
L
| GGT
G
| CCA
P
| GTT
V
| CTT
L
| TCA
S
| GAT
D
| GTT
V
| GAG
E
|
L1b
| TCG
S
| – | – | – | – | – | – | – | – | – | – | – | – | – | GAA
E
| |
L1c
| – | – | – | – | – | – | – | – | CCC
P
| – | – | – | – | GTC
V
| – | |
L1d
| – | – | – | – | – | – | TTG
L
| – | – | – | – | – | – | – | – | |
L1e
| – | – | – | – | – | – | – | – | – | – | – | TCG
S
| – | – | – | |
L2
| LDH-2 | – | – | – | – | – | – | – | – | – | – | – | – | AAT
N
| – | – |
L3
| LDH-3 | – | AAG
K
| – | – | – | – | – | – | – | – | – | – | – | – | – |
L4
| LDH-4 | – | – | CGA
R
| CGA
R
| GTC
V
| – | – | CGT
R
| – | GGT
G
| – | – | – | – | – |
L5
| LDH-5 | – | – | – | – | – | TCA
S
| – |
–
| – | – | CCT
P
| – | – | – | – |
Nucleotide sequences of the ldh gene in worldwide Plasmodium falciparum isolates
Origin of P. falciparum |
L1a
|
L1b
|
L1c
|
L1d
|
L1e
|
L2
|
L3
|
L4
|
L5
|
---|---|---|---|---|---|---|---|---|---|
LDH-1 | LDH-2 | LDH-3 | LDH-4 | LDH-5 | |||||
Cambodiac | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
P. R. Chinac | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 1 |
Indonesiaa | 0 (133)d | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Indiaa | 2 (46)d | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Irana | 6 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Laosc | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Malaysiac | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
The Philippinesc | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Thailandb | 53 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Vietnamc | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
The Gambiac | 54 | 0 | 0 | 0 | 0 | 11 | 0 | 0 | 0 |
Ghanac | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Madagascara | 0 (126)d | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
Malic | 14 | 0 | 0 | 0 | 1 | 8 | 0 | 0 | 0 |
Mozambiquec | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Senegalc | 54 | 0 | 0 | 0 | 0 | 8 | 0 | 0 | 0 |
Tanzaniac | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Ugandac | 7 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Brazilc | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Columbiac | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
El Salvadorc | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
French Guianac | 22 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Hondurasc | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Total | 230 | 1 | 1 | 1 | 1 | 31 | 1 | 1 | 1 |
Signature of negative purifying selection on ldh
Distribution of ldh alleles in Plasmodium falciparum populations
South America | Africa | |
---|---|---|
Africa | 0.00167 (0.12613 ± 0.0309) | – |
Asia | − 0.01592 (0.99099 ± 0.0030) | 0.01569* (0.00000 ± 0.0000) |
Evolutionary relationships of Plasmodium spp. ldh genes in mammals
Species | Host | n | Size (bp) | nsSNP | sSNP | Allele | Isoform |
π
|
---|---|---|---|---|---|---|---|---|
P. falciparum
|
Homo sapiens
| 268 | 918 | 8 | 7 | 9 | 5 | 0.0004 |
P. vivax
a
|
Homo sapiens
| 49 | 931 | 21 | 10 | 11 | 9 | 0.0021 |
P. ovale
b
|
Homo sapiens
| 3 | 951 | 5 | 27 | 3 | 3 | 0.0208 |
P. malariae
d
|
Homo sapiens
| 1 | 898 | ND | ND | 1 | 1 | ND |
P. praefalciparum
c
|
Gorilla gorilla gorilla
| 4 | 821 | 1 | 1 | 3 | 2 | 0.0013 |
P. alderi
c
|
Gorilla gorilla gorilla
| 4 | 770 | 0 | 3 | 4 | 1 | 0.0022 |
P. billcolinsi
c
|
Gorilla gorilla gorilla
| 1 | 770 | ND | ND | 1 | 1 | ND |
P. reichenowi
c
|
Pan troglodytes
| 11 | 822 | 0 | 9 | 10 | 1 | 0.0025 |
P. gaboni
c
|
Pan troglodytes
| 15 | 770 | 1 | 9 | 14 | 3 | 0.0030 |
P. blacklocki
c
|
Pan troglodytes
| 3 | 770 | 1 | 1 | 3 | 2 | 0.0017 |
P. cynomolgi
d
|
Macaca fascicularis
| 1 | 770 | ND | ND | 1 | 1 | ND |
P. knowlesi
d
|
Macaca fascicularis
| 1 | 770 | ND | ND | 1 | 1 | ND |