Deleterious amino acid polymorphisms in Arabidopsis thaliana and rice

Abstract

Plant genetic diversity has been mainly investigated with neutral markers, but large-scale DNA sequencing projects now enable the identification and analysis of different classes of genetic polymorphisms, such as non-synonymous single nucleotide polymorphisms (nsSNPs) in protein coding sequences. Using the SIFT and MAPP programs to predict whether nsSNPs are tolerated (i.e., effectively neutral) or deleterious for protein function, genome-wide nsSNP data from Arabidopsis thaliana and rice were analyzed. In both species, about 20% of polymorphic sites with nsSNPs were classified as deleterious; they segregate at lower allele frequencies than tolerated nsSNPs due to purifying selection. Furthermore, A. thaliana accessions from marginal populations show a higher relative proportion of deleterious nsSNPs, which likely reflects differential selection or demographic effects in subpopulations. To evaluate the sensitivity of predictions, genes from model and crop plants with known functional effects of nsSNPs were inferred with the algorithms. The programs predicted about 70% of nsSNPs correctly as tolerated or deleterious, i.e., as having a functional effect. Forward-in-time simulations of bottleneck and domestication models indicated a high power to detect demographic effects on nsSNP frequencies in sufficiently large datasets. The results indicate that nsSNPs are useful markers for analyzing genetic diversity in plant genetic resources and breeding populations to infer natural/artificial selection and genetic drift.