Indigenous evolution of Plasmodium falciparum pyrimethamine resistance multiple times in Africa.
Indigenous evolution of Plasmodium falciparum pyrimethamine resistance multiple times in Africa.
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DOI：
10.1093/jac/dkn482
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发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
Kobayakawa T
中科院分区：
文献类型：
--
作者：
Mita T;Tanabe K;Takahashi N;Culleton R;Ndounga M;Dzodzomenyo M;Akhwale WS;Kaneko A;Kobayakawa T
恶性疟原虫对乙胺嘧啶的抗性是由编码二氢叶酸还原酶（DHFR）的基因突变赋予的。众所周知，DHFR 双突变体在多个地理区域独立进化，而非洲流行的三突变体似乎起源于东南亚。在这项研究中，我们调查了其他三重突变体是否可能在非洲独立进化。我们确定了从三个非洲国家（刚果共和国、加纳和肯尼亚）收集的 159 个分离株的 DHFR 位点上游 4.49 kb 和下游 1.48 kb 之间的 5 个微卫星位点的 DHFR 基因型和单倍型。 CIRNI 型 DHFR 三重突变体（在氨基酸位置 51、59 和 108 处有下划线突变）在刚果共和国 (82%) 和加纳 (81%) 占主导地位，在肯尼亚 (27%) 是第二流行的，其中 CICNI 型 DHFR 双突变体占主导地位。在 DHFR 三重突变体中鉴定出三种不同的微卫星单倍型。一种单倍型与起源于东南亚的单倍型相同。另外两种单倍型发生在加纳和肯尼亚，它们是独特的，之前未被描述，并且与在同一地点发现的两种 DHFR 双突变体相同。这项研究为非洲乙胺嘧啶耐药性的独特、多重独立进化提供了强有力的证据。在肯尼亚和加纳或东非和西非的邻近国家，三突变体从双突变体的本土进化似乎是逐步发生的。
Resistance to pyrimethamine in Plasmodium falciparum is conferred by mutations in the gene encoding dihydrofolate reductase (DHFR). It is known that DHFR double mutants have evolved independently in multiple geographic areas, whereas the triple mutant prevalent in Africa appears to have originated in south-east Asia. In this study, we investigated whether other triple mutants may have evolved independently in Africa. We determined the DHFR genotypes and haplotypes of five microsatellite loci flanking the DHFR locus between 4.49 kb upstream and 1.48 kb downstream of 159 isolates collected from three African countries (Republic of Congo, Ghana and Kenya). The CIRNI type of DHFR triple mutant (with mutations underlined at amino acid positions 51, 59 and 108) was predominant in the Republic of Congo (82%) and Ghana (81%) and was the second most prevalent in Kenya (27%), where the CICNI type of DHFR double mutant was dominant. Three distinct microsatellite haplotypes were identified in the DHFR triple mutant. One haplotype was identical to that originating in south-east Asia. The other two haplotypes occurred in Ghana and Kenya, which were unique, previously undescribed and identical to those of the two DHFR double mutants found in the same locations. This study presents strong evidence for the unique, multiple independent evolution of pyrimethamine resistance in Africa. Indigenous evolution of the triple mutant from the double mutant appears to have occurred in a step-wise manner in Kenya and Ghana or in nearby countries in east and west Africa.
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DOI：
10.4269/ajtmh.1996.55.209
发表时间：
1996-08-01
影响因子：
3.3
作者：
Reeder, JC;Rieckmann, KH;Cowman, AF
通讯作者：
Cowman, AF
DOI：
10.1073/pnas.94.4.1124
发表时间：
1997-02-18
影响因子：
11.1
作者：
Sirawaraporn, W;Sathitkul, T;Santi, DV
通讯作者：
Santi, DV
影响因子：
168.9
作者：
Roper, C;Pearce, R;Sharp, B
通讯作者：
Sharp, B
影响因子：
6.4
作者：
Certain, Laura K.;Briceno, Marnie;Sibley, Carol Hopkins
通讯作者：
Sibley, Carol Hopkins
影响因子：
6.4
作者：
Maiga, Oumou;Djimde, Abdoulaye A.;Clain, Jerome
通讯作者：
Clain, Jerome