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Detection of selection utilizing molecular phylogenetics: a possible approach.

ABSTRACT: The neutral theory of molecular evolution (Kimura 1985) is the basis for most current statistical tests for detecting selection, mainly using polymorphism data within species, divergence data between species, and/or genomic structures like linkage disequilibrium (Wang et al. 2006). In most cases informative tests can only be constructed with ample variations within these parameters and many common tests are difficult to formulate when identity-by-descent is not clear, for example in gene families or repetitive elements. With the current progress being made toward whole-genome sequencing and re-sequencing efforts, as well as protein sequencing via tandem mass spectrometry where genomic sequencing is lacking, we felt it was necessary to re-visit possible methods for rapid screening and detection of evolutionary outliers. These outliers might be of interest for other research, such as candidate gene association studies or genome annotations, drug- and disease-target searches, and functional studies. We focused on methods that would work on both protein and nucleotide data, could be used on large gene or protein domain families, and could be generated quickly in order for "first pass" annotation of large scale data. For these reasons, we chose properties of trees generated routinely in molecular phylogenetic studies; genetic distance, tree shape and balance, and internal node statistics (Heard 1992). Our current research looking at protein domain family data and phylogenetic trees from PFAM (Finn et al. 2008) suggests this approach towards detecting evolutionary outliers is feasible, but additional work will be necessary to determine the parameters that suggest either positive or negative selection is occurring in specific gene families. This is particularly true when other factors such as rapid duplication and deletion of genes containing these domains is taking place, and we suggest phylogenetic statistics may be useful in combination with existing methodologies for detailed studies of gene family data.

SUBMITTER: Yang M

PROVIDER: S-EPMC3980844 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Detection of selection utilizing molecular phylogenetics: a possible approach.

Yang Ming M Wyckoff Gerald J GJ

Genetica 20110313 5

The neutral theory of molecular evolution (Kimura 1985) is the basis for most current statistical tests for detecting selection, mainly using polymorphism data within species, divergence data between species, and/or genomic structures like linkage disequilibrium (Wang et al. 2006). In most cases informative tests can only be constructed with ample variations within these parameters and many common tests are difficult to formulate when identity-by-descent is not clear, for example in gene familie ...[more]

PMID: 21400220

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Project description:Oridonin is a diterpenoid with anti-cancer activity that occurs in the Chinese medicinal plant Isodon rubescens and some related species. While the bioactivity of oridonin has been well studied, the extent of natural variation in the production of this compound is poorly known. This study characterizes natural variation in oridonin production in order to guide selection of populations of Isodon with highest oridonin yield. Different populations of I. rubescens and related species were collected in China, and their offspring were grown in a greenhouse. Samples were examined for oridonin content, genotyped using 11 microsatellites, and representatives were sequenced for three phylogenetic markers (ITS, rps16, trnL-trnF). Oridonin production was mapped on a molecular phylogeny of the genus Isodon using samples from each population as well as previously published Genbank sequences. Oridonin has been reported in 12 out of 74 species of Isodon examined for diterpenoids, and the phylogeny indicates that oridonin production has arisen at least three times in the genus. Oridonin production was surprisingly consistent between wild-collected parents and greenhouse-grown offspring, despite evidence of gene flow between oridonin-producing and non-producing populations of Isodon. Additionally, microsatellite genetic distance between individuals was significantly correlated with chemical distance in both parents and offspring. Neither heritability nor correlation with genetic distance were significant when the comparison was restricted to only populations of I. rubescens, but this result should be corroborated using additional samples. Based on these results, future screening of Isodon populations for oridonin yield should initially prioritize a broad survey of all species known to produce oridonin, rather than focusing on multiple populations of one species, such as I. rubescens. Of the samples examined here, I. rubescens or I. japonicus from Henan province would provide the best source of oridonin.

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Detection of selection utilizing molecular phylogenetics: a possible approach.

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Detection of selection utilizing molecular phylogenetics: a possible approach.

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