The role of deleterious substitutions in crop genomes

Abstract

Populations continually incur new mutations with fitness effects ranging from lethal to adaptive. While the distribution of fitness effects of new mutations is not directly observable, many mutations likely either have no effect on organismal fitness or are deleterious. Historically, it has been hypothesized that a population may carry many mildly deleterious variants as segregating variation, which reduces the mean absolute fitness of the population. Recent advances in sequencing technology and sequence conservation-based metrics for inferring the functional effect of a variant permit examination of the persistence of deleterious variants in populations. The issue of segregating deleterious variation is particularly important for crop improvement, because the demographic history of domestication and breeding allows deleterious variants to persist and reach moderate frequency, potentially reducing crop productivity. In this study, we use exome resequencing of 15 barley accessions and genome resequencing of 8 soybean accessions to investigate the prevalence of deleterious single nucleotide polymorphisms (SNPs) in the protein-coding regions of the genomes of two crops. We conclude that individual cultivars carry hundreds of deleterious SNPs on average, and that nonsense variants make up a minority of deleterious SNPs. Our approach identifies known phenotype-altering variants as deleterious more frequently than the genome-wide average, suggesting that putatively deleterious variants are likely to affect phenotypic variation. We also report the implementation of a SNP annotation tool BAD_Mutations that makes use of a likelihood ratio test based on alignment of all currently publicly available Angiosperm genomes.

Incomplete Dominance of Deleterious Alleles Contributes Substantially to Trait Variation and Heterosis in Maize

“…Most previous work on genomic prediction, however, focuses exclusively on the statistical properties of models, ignoring potentially useful biological information (but see Edwards et al, [68] for a recent example). Identifying deleterious alleles may prove a useful tool for crop breeding [69], and our results suggest that incorporating additional annotations-in particular information on evolutionary constraint-can provide additional, inexpensive benefits to existing genomic prediction frameworks.…”

Deleterious alleles in the context of domestication, inbreeding, and selection

“…A similar phenomenon has been reported for domestic horse genomes, where an excess of deleterious mutations is thought to be caused by domestication and inbreeding (Schubert et al., ). Also in crops, deleterious mutations seem to have accumulated in domestic lineages (Kono et al., ; Lu et al., ).…”

“…A different approach is to assess the mutational load in genes known to affect phenotypic traits of interest. In plants, such genes were shown to contain proportionally more deleterious variants (Kono et al., ; Lu et al., ; Mezmouk & Ross‐Ibarra, ). The linkage of deleterious variants to genes under balancing selection could also lead to a local overrepresentation of deleterious variants.…”

Identification of candidate domestication‐related genes with a systematic survey of loss‐of‐function mutations

“…In many previous studies, it has been shown that crop plants experienced a strong selection pressure during the domestication process (Gepts, ; Zohary, ; Purugganan and Fuller, ), which often results in the independent appearance of multiple spontaneous adaptive mutations, most of which are base substitutions (Hall, ). The process of increased prevalence (an increase in the number, frequency and/or proportion) of deleterious mutations in domesticated species, has been described as the ‘cost of domestication’ (Kono et al ., ; Moyers et al ., ). An excess of non‐synonymous substitutions was observed in different domesticated germplasm (Liu et al .…”

“…Recently, the effects of domestication on the genome have been presented as the ‘cost of domestication’ hypothesis. According to this, domesticated species have acquired an increased prevalence (an increase in the number, frequency and/or proportion) in deleterious genetic variants during the process of domestication (Kono et al ., ; Moyers et al ., ). In different crop species (rice, maize, barley, soybean and sunflower), an increased proportion of non‐synonymous mutations in domesticated taxa relative to their wild progenitors has been documented (Mezmouk and Ross‐Ibarra, ; Renaut and Rieseberg, ; Kono et al ., ; Liu et al .…”