On the abundance, amino acid composition, and evolutionary dynamics of low-complexity regions in proteins

DePristo, Mark A.; Zilversmit, Martine; Hartl, Daniel L.

doi:10.1016/j.gene.2006.03.023

Cited by 110 publications

(123 citation statements)

References 50 publications

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“…The genome of P. falciparum comprises approximately 82% A-T nucleotide pairs (34), ref lecting a strong mutational bias toward A or T (25). We estimated the mutation matrix (Table S3) using a genome-wide collection of 1,105 SNPs) in intergenic regions, culled from publicly available sequencing reads from P. falciparum and its sister species P. reichenowi.…”

Section: Resultsmentioning

confidence: 99%

Stepwise acquisition of pyrimethamine resistance in the malaria parasite

Lozovsky

Chookajorn

Brown

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The spread of high-level pyrimethamine resistance in Africa threatens to curtail the therapeutic lifetime of antifolate antimalarials. We studied the possible evolutionary pathways in the evolution of pyrimethamine resistance using an approach in which all possible mutational intermediates were created by site-directed mutagenesis and assayed for their level of drug resistance. The coding sequence for dihydrofolate reductase (DHFR) from the malaria parasite Plasmodium falciparum was mutagenized, and tests were carried out in Escherichia coli under conditions in which the endogenous bacterial enzyme was selectively inhibited. We studied 4 key amino acid replacements implicated in pyrimethamine resistance: N51I, C59R, S108N, and I164L. Using empirical estimates of the mutational spectrum in P. falciparum and probabilities of fixation based on the relative levels of resistance, we found that the predicted favored pathways of drug resistance are consistent with those reported in previous kinetic studies, as well as DHFR polymorphisms observed in natural populations. We found that 3 pathways account for nearly 90% of the simulated realizations of the evolution of pyrimethamine resistance. The most frequent pathway (S108N and then C59R, N51I, and I164L) accounts for more than half of the simulated realizations. Our results also suggest an explanation for why I164L is detected in Southeast Asia and South America, but not at significant frequencies in Africa.adaptive landscape ͉ drug resistance ͉ evolution

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Section: Resultsmentioning

confidence: 99%

Stepwise acquisition of pyrimethamine resistance in the malaria parasite

Lozovsky

Chookajorn

Brown

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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266

328

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“…This idea was incorporated in a null model by Dieringer and Schlö tterer (2003; see Figure 1) but AT bias was not proposed as a primary explanation for differences between species. Depristo et al (2006) proposed that AT bias accounts for variation in abundance of low-complexity regions in proteins. We suggest that the explanation will apply most strongly to microsatellites (as the units of lowest complexity and highest slippage) and that it should apply even more strongly to nonprotein sequences than to constrained coding ones.…”

Section: à7mentioning

confidence: 99%

An Unusually Low Microsatellite Mutation Rate in Dictyostelium discoideum, an Organism With Unusually Abundant Microsatellites

et al. 2007

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The genome of the social amoeba Dictyostelium discoideum is known to have a very high density of microsatellite repeats, including thousands of triplet microsatellite repeats in coding regions that apparently code for long runs of single amino acids. We used a mutation accumulation study to see if unusually high microsatellite mutation rates contribute to this pattern. There was a modest bias toward mutations that increase repeat number, but because upward mutations were smaller than downward ones, this did not lead to a net average increase in size. Longer microsatellites had higher mutation rates than shorter ones, but did not show greater directional bias. The most striking finding is that the overall mutation rate is the lowest reported for microsatellites: $1 3 10 À6 for 10 dinucleotide loci and 6 3 10 À6 for 52 trinucleotide loci (which were longer). High microsatellite mutation rates therefore do not explain the high incidence of microsatellites. The causal relation may in fact be reversed, with low mutation rates evolving to protect against deleterious fitness effects of mutation at the numerous microsatellites.M ICROSATELLITES, also known as simple sequence repeats, are long stretches of a short (1-6 bp), tandemly repeated DNA unit, such as the motif CAA repeated 20 times. Microsatellites are common throughout eukaryotic genomes and their lengths are often highly polymorphic, making them powerful markers for use in genetic mapping

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“…Protein dizilimlerinde yer alan ve amino asit içeriklerinde çok az ya da hiçbir farklılık göstermeyen düşük karmaşıklığa sahip bölgeler (low-complexity regions (LCR)) ökaryot genomlarında oldukça yaygındır (38,39). LCR'lerde yer alan farklılıklar sadece tek bir amino asit ya da birkaç amino asit düzeyinde olabilmektedir (40). T. annulata genomunda da LCR'ler oldukça yaygın olarak görülmektedir.…”

Section: Yöntemlerunclassified

Selection of Genetic Markers to Determine Diversity in Theileria annulata Populations after Recombination

Bilgiç¹,

Ünlü²,

Aksulu³

et al. 2017

TurkiyeParazitolDerg

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ÖZAmaç: Theileria annulata popülasyonlarında rekombinasyon sonrası oluşacak genetik çeşitliliğin ve rekombinasyonun yoğun olduğu kromozomal bölgelerin tespit edilmesi amacıyla kullanılacak polimorfik mini ve mikrosatellite markerlerin belirlenmesidir. Yöntemler: Markerlerin belirlenmesi amacıyla Unipro UGENE programı kullanılmıştır. T. annulata'nın rastgele karıştırılmış genomik dizilimlere göre gerçek DNA diziliminde 10 kat fazla tandem tekrar (TR) belirleyen skor, eşik değer olarak belirlenmiştir. Tekrarlı motif benzerliği %96-100 arasında bulunan, minimum tekrar sayısı en az üç ve minimum tandem boyutu minisatellite bölgeler için en az üç nükleotid ve mikrosatellite bölgeler için en az altı nükleotid olan TR'ler suffix array algoritması kullanılarak tüm genom boyunca taranmıştır. Bulgular: Tarama sonrası 359 minisatellite ve 8973 mikrosatellite bölge belirlenmiştir. TR'ler tüm genom boyunca tek tek taranarak; T. annulata'nın kromozomları üzerindeki yerleşim yerlerine, motiflerin benzerliğine (>%96), tekrar sayıları ile tek bölgeyi temsil etmesine, bölgelerin uzunluklarına (<1500 bp) ve primer tasarlanmaya uygun korunmuş bölgeler içermesine bakılarak mini ve mikrosatellite bölgeler belirlenmiştir. Belirlenen bölgeleri çoğaltmada kullanılacak primerler, korunmuş bölgelerden tasarlanmış ve her bir primer, T. annulata'nın farklı izolatları kullanılarak değerlendirilmiştir. Sonuç: Bu çalışmada, T.annulata popülasyonlarındaki çeşitliliğinin belirlenmesi amacıyla daha önce belirlenen markerlere ilave olarak kullanılabile-cek, farklı kromozomlar üzerinde bulunan toplam 13 mini ve mikrosatellite marker seçilmiştir. Anahtar Kelimeler: Theileria annulata, rekombinasyon, satellit marker Geliş Tarihi: 17.06.2016Kabul Tarihi: 21.12.2016 ABSTRACT Objective: Selecting polymorphic mini-and microsatellite markers to determine genetic diversity and chromosomal regions exhibiting elevated rates of recombination in Theileria annulata populations after recombination. Methods: The Unipro UGENE software was used to select markers. A score at which 10 times more tandem repeats (TRs) were identified in the real DNA sequence than those in the scrambled sequences of T. annulata was used as the cutoff. TRs containing minimum three nucleotides in length for microsatellite and six nucleotides for minisatellite regions and having a repeat motif identity between 96%-100% with the unit size repeated minimum three times were screened through the whole genome using the suffix array algorithm.Results: A total of 359 minisatellites and 8973 microsatellites were identified. TRs were screened one by one through the whole genome; mini-and microsatellites representing a single region and having suitable regions for primer design were selected based on their localization on T. annulata chromosomes, their repeat motif identity (>96%), and their repeat length (<1500 bp). The primers used to amplify selected candidates were designed, and each primer was used to check 27 different isolates of T. annulata. Conclusion: In the present study, a total of 13 po...

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On the abundance, amino acid composition, and evolutionary dynamics of low-complexity regions in proteins

Cited by 110 publications

References 50 publications

Stepwise acquisition of pyrimethamine resistance in the malaria parasite

Stepwise acquisition of pyrimethamine resistance in the malaria parasite

An Unusually Low Microsatellite Mutation Rate in Dictyostelium discoideum, an Organism With Unusually Abundant Microsatellites

Selection of Genetic Markers to Determine Diversity in Theileria annulata Populations after Recombination

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