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

Abstract

Each individual has a certain number of harmful mutations in its genome. These mutations can lower the fitness of the individual carrying them, dependent on their dominance and selection coefficient. Effective population size, selection, and admixture are known to affect the occurrence of such mutations in a population. The relative roles of demography and selection are a key in understanding the process of adaptation. These are factors that are potentially influenced and confounded in domestic animals. Here, we hypothesize that the series of events of bottlenecks, introgression, and strong artificial selection associated with domestication increased mutational load in domestic species. Yet, mutational load is hard to quantify, so there are very few studies available revealing the relevance of evolutionary processes. The precise role of artificial selection, bottlenecks, and introgression in further increasing the load of deleterious variants in animals in breeding and conservation programmes remains unclear. In this paper, we review the effects of domestication and selection on mutational load in domestic species. Moreover, we test some hypotheses on higher mutational load due to domestication and selective sweeps using sequence data from commercial pig and chicken lines. Overall, we argue that domestication by itself is not a prerequisite for genetic erosion, indicating that fitness potential does not need to decline. Rather, mutational load in domestic species can be influenced by many factors, but consistent or strong trends are not yet clear. However, methods emerging from molecular genetics allow discrimination of hypotheses about the determinants of mutational load, such as effective population size, inbreeding, and selection, in domestic systems. These findings make us rethink the effect of our current breeding schemes on fitness of populations.

Keywords: deleterious alleles; domestication; genetic load; inbreeding; selection.

Figure 1

Genomic consequences of inbreeding. When parents are related, two identical haplotypes can be passed on to their offspring that are identical by descent. Therefore, no genetic variation exists between the two inherited copies in the inbred offspring. Such homozygous stretches (ROH: Runs Of Homozygosity) can be seen as long homozygous regions without polymorphisms in individual genomes. In ROH, harmful mutations have a higher chance of becoming homozygous and being expressed because the haplotypes carrying the harmful mutation stem from a common ancestor

Figure 2

Mutational load in Sus scrofa and Gallus gallus. Mutational load in individual genomes, calculated as the ratio of predicted deleterious heterozygous sites over synonymous heterozygous sites. (a) Pigs. ED = European domestic; EW = European wild; AD = Asian domestic; AWN = North Asian wild; AWS = South Asian wild. (b) chicken AF = African village chicken, putatively evolutionary closer to red jungle fowl. WL = commercial white layer lines

Figure 3

Genetic hitch‐hiking of deleterious alleles in selected regions. Under neutrality, deleterious alleles are present in a population at low frequency (indicated in red). If a deleterious allele lies on the same haplotype as a selected variant (indicated in blue), linkage is strong, and if the selective advantage s of the advantageous allele is stronger than the summed selection coefficient against all (slightly) deleterious alleles ∑s, the harmful mutations will rise in frequency despite their deleterious nature as demonstrated in the allele frequency spectrum in the population before – and after selection

Figure 4

Deleterious alleles within and outside ROH in chicken. Proportion of deleterious homozygous variants within and outside ROH‐regions in three different white layer lines. Paired t test Line1 p = 6.65e‐05; Line2 p = 1.11e‐07; Line3 p = 5.684e‐07

Figure 5

Distribution of deleterious alleles within the genomes of commercial pigs and wild boars. (a) The x‐axis represents length of the chromosome, and numbers on the y‐axis indicate chromosomes. Blue horizontal bars represent ROH within the genome of an individual, red crosses pinpoint the location of predicted deleterious variants within ROH, and black crosses mark the position of homozygous deleterious alleles outside ROH. (b) Violin plots summarizing the frequency of homozygous deleterious alleles within and outside ROH‐regions. (c) The proportion of homozygous deleterious alleles compared to neutral homozygous alleles within and outside ROH‐regions