Estimation of the neutrality index

N Stoletzki, A Eyre-Walker - Molecular biology and evolution, 2011 - academic.oup.com
N Stoletzki, A Eyre-Walker
Molecular biology and evolution, 2011academic.oup.com
Abstract The McDonald–Kreitman (MK) test is a simple and widely used test of selection in
which the numbers of nonsilent and silent substitutions (D n and D s) are compared with the
numbers of nonsilent and silent polymorphisms (P n and P s). The neutrality index (NI= D s P
n/D n P s), the odds ratio (OR) of the MK table, measures the direction and degree of
departure from neutral evolution. The mean of NI values across genes is often taken to
summarize patterns of selection in a species. Here, we show that this leads to statistical bias …
Abstract
The McDonald–Kreitman (MK) test is a simple and widely used test of selection in which the numbers of nonsilent and silent substitutions (Dn and Ds) are compared with the numbers of nonsilent and silent polymorphisms (Pn and Ps). The neutrality index (NI = DsPn/DnPs), the odds ratio (OR) of the MK table, measures the direction and degree of departure from neutral evolution. The mean of NI values across genes is often taken to summarize patterns of selection in a species. Here, we show that this leads to statistical bias in both simulated and real data to the extent that species, which show a pattern of adaptive evolution, can apparently be subject to weak purifying selection and vice versa. We show that this bias can be removed by using a variant of the Cochran—Mantel–Haenszel procedure for estimating a weighted average OR. We also show that several point estimators of NI are statistically biased even when cutoff values are employed. We therefore suggest that a new statistic be used to study patterns of selection when data are sparse, the direction of selection: DoS = Dn/(Dn + Ds) − Pn/(Pn + Ps).
Oxford University Press