Accuracy and Power of Statistical Methods for Detecting Adaptive Evolution in Protein Coding Sequences and for Identifying Positively Selected Sites

Wong, Wendy S. W.; Yang, Ziheng; Goldman, Nick; Nielsen, Rasmus

doi:10.1534/genetics.104.031153

Cited by 554 publications

(522 citation statements)

References 37 publications

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“…Recently, alternative approaches based on maximum-likelihood models have been suggested that potentially provide more accurate estimates of d N /d S ratios and allow the identification of species-specific PSS (Yang and Bielawski, 2000;. In simulations, Wong et al (2004) demonstrated that the maximum-likelihood method has a good power and accuracy in detecting positive selection. It is particularly appropriate for detecting selection in MHC genes, where positive selection could be acting simultaneously in groups of codons (Suzuki and Nei, 2004).…”

Section: Discussionmentioning

confidence: 99%

Neutral versus adaptive genetic variation in parasite resistance: importance of major histocompatibility complex supertypes in a free-ranging primate

et al. 2007

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Current discussions in evolutionary ecology and conservation genetics focus on the relative importance of using selective neutral markers or markers of coding genes to identify adaptive and evolutionary relevant processes. Genetic diversity might be particularly important in immune genes (e.g., in genes of the major histocompatibility complex, MHC), which are influencing pathogen and parasite resistance. We investigated the effects of neutral versus adaptive genetic variation in parasite resistance in a natural population of fat-tailed dwarf lemurs (Cheirogaleus medius). No association between neutral overall individual genetic diversity and parasite load could be detected. In 149 individuals, we identified 50 MHC class II alleles of the functionally important duplicated DRB locus. The investigation of the functional importance of immune gene (MHC) diversity and parasite selection in natural populations is often problematic due to extensive polymorphism in the MHC genes and restrictions in available sample sizes. Here, for the first time we applied an approach that has been developed in human medical studies. Eleven MHC class II supertypes were identified based on shared antigen-binding similarities. The number of individual MHC supertypes had no influence on the nematode burden. However, we found evidence for a specific MHC supertype (supertype 1) that was linked to infected individuals, a higher number of different nematode infections and high intensity of infection per individual. Moreover, one rare MHC supertype (supertype 7) was revealed to be advantageous with respect to parasite burden. Thus, our results add evidence to the small body of studies that show significant associations between specific MHC constitutions and naturally occurring parasites in the complexity of natural populations.

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Section: Discussionmentioning

confidence: 99%

Neutral versus adaptive genetic variation in parasite resistance: importance of major histocompatibility complex supertypes in a free-ranging primate

et al. 2007

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“…For the serine peptidase family and each CRN subfamily, we firstly used the site-specific models [22,45,46] to identify positively selected codon sites in Bd and in oomycetes or bacteria, respectively. In this analysis, we compared models M1a vs .…”

Section: Methodsmentioning

confidence: 99%

Evidence for acquisition of virulence effectors in pathogenic chytrids

et al. 2011

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BackgroundThe decline in amphibian populations across the world is frequently linked to the infection of the chytrid fungus Batrachochytrium dendrobatidis (Bd). This is particularly perplexing because Bd was only recently discovered in 1999 and no chytrid fungus had previously been identified as a vertebrate pathogen.ResultsIn this study, we show that two large families of known virulence effector genes, crinkler (CRN) proteins and serine peptidases, were acquired by Bd from oomycete pathogens and bacteria, respectively. These two families have been duplicated after their acquisition by Bd. Additional selection analyses indicate that both families evolved under strong positive selection, suggesting that they are involved in the adaptation of Bd to its hosts.ConclusionsWe propose that the acquisition of virulence effectors, in combination with habitat disruption and climate change, may have driven the Bd epidemics and the decline in amphibian populations. This finding provides a starting point for biochemical investigations of chytridiomycosis.

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“…Models are compared by a log-likelihood ratio test, LRT (LRT ¼ À2 times the difference in log-likelihood tested against a w 2 -distribution with the number of degrees of freedom equal to the number of additional random effects). It should be noted that the use of two degrees of freedom for the M8 vs M7 comparisons and one degree of freedom for the M8a vs M8 comparisons is considered conservative (Swanson et al, 2003;Wong et al, 2004).…”

Section: Sequence Analysismentioning

confidence: 99%

The evolution of novelty in conserved genes; evidence of positive selection in the Drosophila fruitless gene is localised to alternatively spliced exons

et al. 2013

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There has been much debate concerning whether cis-regulatory or coding changes are more likely to produce evolutionary innovation or adaptation in gene function, but an additional complication is that some genes can dramatically diverge through alternative splicing, increasing the diversity of gene function within a locus. The fruitless gene is a major transcription factor with a wide range of pleiotropic functions, including a fundamental conserved role in sexual differentiation, species-specific morphology and an important influence on male sexual behaviour. Here, we examine the structure of fruitless in multiple species of Drosophila, and determine the patterns of selective constraint acting across the coding region. We found that the pattern of selection, estimated from the ratio of non-synonymous to synonymous substitutions, varied considerably across the gene, with most regions of the gene evolutionarily conserved but with several regions showing evidence of divergence as a result of positive selection. The regions that showed evidence of positive selection were found to be localised to relatively consistent regions across multiple speciation events, and are associated with alternative splicing. Alternative splicing may thus provide a route to gene diversification in key regulatory loci.

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Accuracy and Power of Statistical Methods for Detecting Adaptive Evolution in Protein Coding Sequences and for Identifying Positively Selected Sites

Cited by 554 publications

References 37 publications

Neutral versus adaptive genetic variation in parasite resistance: importance of major histocompatibility complex supertypes in a free-ranging primate

Neutral versus adaptive genetic variation in parasite resistance: importance of major histocompatibility complex supertypes in a free-ranging primate

Evidence for acquisition of virulence effectors in pathogenic chytrids

The evolution of novelty in conserved genes; evidence of positive selection in the Drosophila fruitless gene is localised to alternatively spliced exons

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