Standard and generalized McDonald-Kreitman test: a website to detect selection by comparing different classes of DNA sites

Egea, Raquel; Casillas, Sònia; Barbadilla, Antonio

doi:10.1093/nar/gkn337

Cited by 135 publications

(130 citation statements)

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“…The exact functions of these genes are unknown, but their location near the 3' end of the left arm between structural protein genes and lysis protein genes suggests that they could encode late-acting proteins. Based on the McDonald-Kreitman test (Egea et al, 2008), gene gp17 is under selection (P = 0.011).…”

Section: Diversity Of P Acnes Phages In the Human Skinmentioning

confidence: 99%

The diversity and host interactions of Propionibacterium acnes bacteriophages on human skin

et al. 2015

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The viral population, including bacteriophages, is an important component of the human microbiota, yet is poorly understood. We aim to determine whether bacteriophages modulate the composition of the bacterial populations, thus potentially playing a role in health or disease. We investigated the diversity and host interactions of the bacteriophages of Propionibacterium acnes, a major human skin commensal implicated in acne pathogenesis. By sequencing 48 P. acnes phages isolated from acne patients and healthy individuals and by analyzing the P. acnes phage populations in healthy skin metagenomes, we revealed that P. acnes phage populations in the skin microbial community are often dominated by one strain. We also found phage strains shared among both related and unrelated individuals, suggesting that a pool of common phages exists in the human population and that transmission of phages may occur between individuals. To better understand the bacterium-phage interactions in the skin microbiota, we determined the outcomes of 74 genetically defined Propionibacterium strains challenged by 15 sequenced phages. Depending on the Propionibacterium lineage, phage infection can result in lysis, pseudolysogeny, or resistance. In type II P. acnes strains, we found that encoding matching clustered regularly interspaced short palindromic repeat spacers is insufficient to confer phage resistance. Overall, our findings suggest that the prey-predator relationship between bacteria and phages may have a role in modulating the composition of the microbiota. Our study also suggests that the microbiome structure of an individual may be an important factor in the design of phage-based therapy.

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Section: Diversity Of P Acnes Phages In the Human Skinmentioning

confidence: 99%

The diversity and host interactions of Propionibacterium acnes bacteriophages on human skin

et al. 2015

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“…Sequences were extracted, aligned, and trimmed following the same methodology described above for the phylogenetic analysis. The tests were implemented with the web server described by Egea et al (2008). For each gene, the neutrality index (NI) was calculated by dividing the ratio of nonsynonymous to synonymous polymorphisms within S. conica (P n /P s ) by the ratio of nonsynonymous to synonymous divergence from a closely related outgroup (see below) species (D n /D s ) (Rand and Kann 1996).…”

Section: Mcdonald-kreitman (Mk) Testsmentioning

confidence: 99%

Positive Selection in Rapidly Evolving Plastid–Nuclear Enzyme Complexes

et al. 2016

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Rates of sequence evolution in plastid genomes are generally low, but numerous angiosperm lineages exhibit accelerated evolutionary rates in similar subsets of plastid genes. These genes include clpP1 and accD, which encode components of the caseinolytic protease (CLP) and acetyl-coA carboxylase (ACCase) complexes, respectively. Whether these extreme and repeated accelerations in rates of plastid genome evolution result from adaptive change in proteins (i.e., positive selection) or simply a loss of functional constraint (i.e., relaxed purifying selection) is a source of ongoing controversy. To address this, we have taken advantage of the multiple independent accelerations that have occurred within the genus Silene (Caryophyllaceae) by examining phylogenetic and population genetic variation in the nuclear genes that encode subunits of the CLP and ACCase complexes. We found that, in species with accelerated plastid genome evolution, the nuclear-encoded subunits in the CLP and ACCase complexes are also evolving rapidly, especially those involved in direct physical interactions with plastid-encoded proteins. A massive excess of nonsynonymous substitutions between species relative to levels of intraspecific polymorphism indicated a history of strong positive selection (particularly in CLP genes). Interestingly, however, some species are likely undergoing loss of the native (heteromeric) plastid ACCase and putative functional replacement by a duplicated cytosolic (homomeric) ACCase. Overall, the patterns of molecular evolution in these plastidnuclear complexes are unusual for anciently conserved enzymes. They instead resemble cases of antagonistic coevolution between pathogens and host immune genes. We discuss a possible role of plastid-nuclear conflict as a novel cause of accelerated evolution.

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“…For example, several recent studies have applied the MK test to putatively functionless (i.e., neutral) vs. putatively functional (i.e., selected) sites in noncoding DNA elements ( Jenkins et al 1995;Ludwig and Kreitman 1995;MacDonald and Long 2005;Ding and Kullo 2006;Casillas et al 2007). Similarly, a wave of recent studies has used closely linked synonymous sites to test for departures in non- coding DNA (Kohn et al 2004;Begun et al 2007;Holloway et al 2007;Egea et al 2008;Jeong et al 2008) or compared synonymous sites and noncoding sites from unlinked genomic regions (Andolfatto 2005;Casillas et al 2007;Egea et al 2008). These applications of the MK test are a departure from the standard assumption of the MK test-that neutral and selected sites are homogenously interdigitated (i.e., compare Figure 1A to Figures 1B and 1C).…”

Section: T He Mcdonald-kreitman (Mk) Test Is a Widely Usedmentioning

confidence: 99%

Controlling Type-I Error of the McDonald–Kreitman Test in Genomewide Scans for Selection on Noncoding DNA

Andolfatto

2008

Genetics

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Departures from the assumption of homogenously interdigitated neutral and putatively selected sites in the McDonald-Kreitman test can lead to false rejections of the neutral model in the presence of intermediate levels of recombination. This problem is exacerbated by small sample sizes, nonequilibrium demography, recombination rate variation, and in comparisons involving more recently diverged species. I propose that establishing significance levels by coalescent simulation with recombination can improve the fidelity of the test in genomewide scans for selection on noncoding DNA. T HE McDonald-Kreitman (MK) test is a widely usedstatistical test of neutral model of evolution originally proposed for nonrecombining protein sequences (McDonald and Kreitman 1991;Nielsen 2005). The test compares within-species polymorphism and between-species divergence for two distinct classes of sites: synonymous sites, which are assumed to be neutral and nonsynonymous sites, which are putative targets of selection. The null model assumes that some fraction, f, of nonsynonymous sites is strongly deleterious and contributes negligibly to polymorphism and divergence. For the remaining nonsynonymous sites, (1 À f ), the ratio of polymorphism to divergence is expected to be identical to that for synonymous sites, if both behave according to the neutral model.Departures from expectations under neutral model are expected if nonsynonymous sites experience negative or positive selection. If the evolution of (nonlethal) nonsynonymous sites in a particular gene is largely governed by negative (or purifying) selection, this will tend to decrease the level of divergence at nonsynonymous sites more strongly than levels of polymorphism (Kimura 1983). The result will be that nonsynonymous sites will exhibit a higher ratio of polymorphism to divergence than putatively neutral synonymous sites. In contrast, if the evolution of nonsynonymous sites is governed primarily by positive selection, this will tend to decrease the ratio of polymorphism to divergence relative to synonymous sites. A departure from the neutral expectation in either direction can be detected by applying a standard statistical test to a 2 3 2 contingency table of polymorphism and divergence counts for synonymous and nonsynonymous sites.An attractive feature of the MK test is that the inference of selection, although not necessarily its mode, is remarkably robust to assumptions about nonequilibrium demography (Nielsen 2001;Eyre-Walker 2002) and recombination rates (Sawyer and Hartl 1992). In the absence of recombination, this robustness stems from the fact that all surveyed sites share the same genealogy and thus the entries of the 2 3 2 table are sufficient statistics (Nielsen 2001). In the presence of recombination, the robustness of the MK test is largely owed to the fact that nonsynonymous and synonymous sites are homogenously interdigitated in protein sequences ( Figure 1A).Using synonymous (or other neutral sites) to test for selection in linked noncoding DNA: Althoug...

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Standard and generalized McDonald-Kreitman test: a website to detect selection by comparing different classes of DNA sites

Cited by 135 publications

References 30 publications

The diversity and host interactions of Propionibacterium acnes bacteriophages on human skin

The diversity and host interactions of Propionibacterium acnes bacteriophages on human skin

Positive Selection in Rapidly Evolving Plastid–Nuclear Enzyme Complexes

Controlling Type-I Error of the McDonald–Kreitman Test in Genomewide Scans for Selection on Noncoding DNA

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