Statistical tests of neutrality of mutations.

Abstract

Mutations in the genealogy of the sequences in a random sample from a population can be classified as external and internal. External mutations are mutations that occurred in the external branches and internal mutations are mutations that occurred in the internal branches of the genealogy. Under the assumption of selective neutrality, the expected number of external mutations is equal to theta = 4Ne mu, where Ne is the effective population size and mu is the rate of mutation per gene per generation. Interestingly, this expectation is independent of the sample size. The number of external mutations is likely to deviate from its neutral expectation when there is selection while the number of internal mutations is less affected by the presence of selection. Statistical properties of the numbers of external mutations and of internal mutations are studied and their relationships to two commonly used estimates of theta are derived. From these properties, several new statistical tests based on a random sample of DNA sequences from the population are developed for testing the hypothesis that all mutations at a locus are neutral.

Spread of an Inactive Form of Caspase-12 in Humans Is Due to Recent Positive Selection

“…A median-joining network was constructed using NETW4.1.0.9 (Bandelt et al 1999;Fluxus). The ratio of the number of nonsynonymous substitutions per nonsynonymous site (K a ) to the number of synonymous substitutions per synonymous site (K s ), K a /K s , and summary statistics (Tajima 1989;Fu and Li 1993;Fu 1997;Fay and Wu 2000) were calculated using DnaSP 4.00 (Rozas et al 2003). Several of these tests compare different estimators of the population mutation parameter, v. Tajima's D compares v estimated from the number of polymorphic sites with v estimated from the nucleotide diversity; negative values indicate an excess of rare variants, whereas positive values indicate an excess of intermediate-frequency variants.…”

Synonymous site variation due to recombination explains higher genetic variability in begomovirus populations infecting non-cultivated hosts

“…In the case of recombination events associated with only one sequence, the event was assigned to the branch leading to the corresponding tip. Using PAUP*, we identified all substitutions that occurred over each ML tree, and calculated g, the total number of substitutions over the phylogeny (Fu & Li, 1993). We then looked at the location within the gene of substitutions that occurred on branches associated with recombination.…”

Haplotypic divergence coupled with lack of diversity at the Arabidopsis thaliana alcohol dehydrogenase locus: roles for both balancing and directional selection?

“…We have applied TAJIMA'S (1989) test of selective neutrality: TAJIMA'S D = 1.825 (0.1 > P > 0.05). FU and LI (1993) present another test based on the distribution of variants on a phylogenetic tree. For this test, we used C. arenosa as an outgroup (see Figure 5) and accordingly excluded one (C at position 1649) of the three singleton nucleotide variants from our total of "external" mutations, q,.…”

“…GAUT and CLEGG (1993a) compared the sequences of one Adh allele from each of two teosintes (Zea luxurians and Zea diploperennis), Adh-IF, Adh-I S , Adhl-C" (OSTERMAN and DENNIS 1989) and three additional alleles of Zea mays and found no evidence of either balancing selection or a selective sweep at the locus. In their study of pearl millet (Pennisetum glaucum), GAUT and CLEGG (1993b) analyzed 20 alleles of Adhl from 10 individuals, 6 of which were wildcollected, and using the tests of TAJIMA (1989) and of Fu and LI (1993), they were again unable to reject the hypothesis that all polymorphisms were neutral.…”