Collected Plasmodium faliciparum GWAS and resistance to antimalarial drugs

Plasmodium falciparum parasite spreads rapidly and widely, if it is out of control. The major prevention is antimalarial drugs. However, drug resistance in parasites has evolved and spread rapidly. In consequence, it’s necessary to launch genome-wide association studies of parasite traits. Previous studies show that mutations in MAL7P1.27 (also known as pfcrt, the gene encoding the P. falciparum CQ resistance transporter) and in the genes encoding P. falciparum dihydrofolate reductase (pfdhfr) and P. falciparum dihydrofolate reductase (pfdhps) have been shown to confer resistance to CQ and SP. Moreover, copy number and/or point mutations at pfmdr1 on chromosome 5 linked to the parasite response to MQ, QN, ART and other antimalarial drugs. Additionally, it has been shown that using 342 genome-wide microsatellite markers and 92 parasite isolates collected from different parts of the world is a more efficient and less-time-consuming way to identify the chromosome segment carrying the pfcrt locus. In the present study, with increase of the number of isolated parasites, it reports the first genome-wide P. falciparum using sensitive method and GWAS of resistance of multiple antimalarial drugs. In general, the authors isolated 189 culture-adapted P. falciparum parasites in vitro culture, from Asia, Africa, America and paua New Guina. …

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Towards an unbiased study of parallel evolution

The investigation of parallel evolution is a powerful paradigm to study mechanisms of adaptation.  This review and opinion paper stresses the fact that although remarkable examples have been studied, molecular bases of adaptation are still poorly understood in the vast majority of cases. In rare examples, a genetic variation has been linked to repeated and independent adaptation. In the examples of Mc1r , multiple mutations occurred in the same gene independently leading to different coat colours in mice.  In humans, lactose tolerance was acquired repeatedly due to mutations occurring independently in the same genes in different populations.  In the paper, authors describe mutations in Pitx1 which have occurred repeatedly in three spine stickleback fish leading to reduced pelvic armor plate which differentiates the sea water from the fresh water specie. These observations have been validated by transgenic animals demonstrating the fact that Pitx1 is the genetic basis of this recurrent phenotype and form of adaptation. As a reader naïve to the field, I found that this paper describes well the obstacles that researchers are facing in the investigation of the molecular basis of adaptation.  Genetic data is sparse and the vast majority of species have not been sequenced. For those …

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Hard selective sweeps do not seem to be the rule in human evolution.

by Ricardo Kanitz, based on the paper by Hernandez et al. published in Science (2011). One of the main topics in evolution is – as it has always been – human evolution. Many new methods are applied first to humans; other methods, which are not applied there, often come to humans at some point anyway. This is particularly true in the field of genomics and it is no surprise since we are talking about our own species’ evolution. The study commented here addresses an interesting general question in the subject. How selection shaped (if at all) our genomes? More specifically, Hernandez and colleagues are interested in the classic signature of selection in genomes, the “selective sweep”. This so-called sweep is simply the reduction of measured diversity in the (genomic) surroundings of a positively selected mutation. This is observed when (1st) a new beneficial mutation appears, (2nd) it rapidly becomes the most common variant in a population and, (3rd) because genomic positions are not physically independent, nearby positions also become more frequent. As we move further away from such positively selected position, we observe a decay of such pattern due to recombination (see cartoon below). Based on functional groundings, the authors …

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