The accumulation of deleterious mutations in rice genomes: a hypothesis on the cost of domestication

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The domestication of the horse ∼5.5 kya and the emergence of mounted riding, chariotry, and cavalry dramatically transformed human civilization. However, the genetics underlying horse domestication are difficult to reconstruct, given the near extinction of wild horses. We therefore sequenced two ancient horse genomes from Taymyr, Russia (at 7.4-and 24.3-fold coverage), both predating the earliest archeological evidence of domestication. We compared these genomes with genomes of domesticated horses and the wild Przewalski's horse and found genetic structure within Eurasia in the Late Pleistocene, with the ancient population contributing significantly to the genetic variation of domesticated breeds. We furthermore identified a conservative set of 125 potential domestication targets using four complementary scans for genes that have undergone positive selection. One group of genes is involved in muscular and limb development, articular junctions, and the cardiac system, and may represent physiological adaptations to human utilization. A second group consists of genes with cognitive functions, including social behavior, learning capabilities, fear response, and agreeableness, which may have been key for taming horses. We also found that domestication is associated with inbreeding and an excess of deleterious mutations. This genetic load is in line with the "cost of domestication" hypothesis also reported for rice, tomatoes, and dogs, and it is generally attributed to the relaxation of purifying selection resulting from the strong demographic bottlenecks accompanying domestication. Our work demonstrates the power of ancient genomes to reconstruct the complex genetic changes that transformed wild animals into their domesticated forms, and the population context in which this process took place.ancient DNA | horse domestication | Przewalski's horse | positive selection | cost of domestication T he domestication of the horse had a far-reaching impact on the sociopolitical and economic trajectories of human societies (1). It not only provided meat and milk (2) but also enabled the development of continent-sized nomadic empires, by transforming warfare and allowing for the rapid spread of goods and information over long distances. However, despite the characterization of the genome of modern horses (3), an understanding of the genetic processes underlying horse domestication is still lacking. In other organisms, such an understanding is usually achieved by comparing the genomes of domesticated species and their wild relatives (4-6), but this approach is not directly applicable to horses. Recent genome-wide analyses have shown that Przewalski's horse, the last truly wild horse population remaining today, is not the direct ancestor of domesticated SignificanceThe domestication of the horse revolutionized warfare, trade, and the exchange of people and ideas. This at least 5,500-ylong process, which ultimately transformed wild horses into the hundreds of breeds living today, is difficult to reconstruct from archeological data...

Section: Resultsmentioning

confidence: 99%

Prehistoric genomes reveal the genetic foundation and cost of horse domestication

Schubert

Jónsson

Chang

et al. 2014

278

281

“…These factors are predicted to increase the relative rate of nonsynonymous to synonymous (dN/dS) substitution, potentially resulting in the fixation of deleterious alleles (11). Previous studies comparing the distribution of polymorphisms between rice and dogs and their closest wild relatives have suggested that this may be the case (12,13). However, the lack of genome-wide polymorphism data in multiple wild accessions has limited these comparisons because of ambiguous assignment of ancestral state.…”

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confidence: 99%

Comparative transcriptomics reveals patterns of selection in domesticated and wild tomato

Koenig

Jiménez‐Gómez²,

Kimura

et al. 2013

338

268

Although applied over extremely short timescales, artificial selection has dramatically altered the form, physiology, and life history of cultivated plants. We have used RNAseq to define both gene sequence and expression divergence between cultivated tomato and five related wild species. Based on sequence differences, we detect footprints of positive selection in over 50 genes. We also document thousands of shifts in gene-expression level, many of which resulted from changes in selection pressure. These rapidly evolving genes are commonly associated with environmental response and stress tolerance. The importance of environmental inputs during evolution of gene expression is further highlighted by large-scale alteration of the light response coexpression network between wild and cultivated accessions. Human manipulation of the genome has heavily impacted the tomato transcriptome through directed admixture and by indirectly favoring nonsynonymous over synonymous substitutions. Taken together, our results shed light on the pervasive effects artificial and natural selection have had on the transcriptomes of tomato and its wild relatives.domestication | biotic stress | abiotic stress D omestication has long served as an important example of severe phenotypic divergence in response to selection. Darwin recognized the parallel between the processes of domestication and adaptation in the wild and used this analogy to emphasize the power of selection in generating phenotypic diversity (1). The genetic basis of domestication-associated phenotypes has been examined in several instances, most notably in maize, rice, tomato, and dogs (reviewed in refs. 2-5). The clear conclusion from these studies is that the rapid phenotypic divergence associated with domestication is often attributable to very few genetic loci (6). Improvements to DNA sequence technologies have allowed studies of the effect of domestication at the whole-genome level. Early population genetic analyses in maize found that very few genes (∼5%) show evidence of positive selection during domestication of maize (7), and recent work using whole-genome resequencing has found a similar proportion of the genome was under positive selection (8). Evidence for strong selective sweeps at a limited number of loci has also been found in rice and dog genomes (9). Together with the previous genetic mapping work, these studies support the model that relatively few mutations experienced extremely strong selection by humans during domestication.Although not the target of direct positive selection, the rest of the genome still experiences a dramatic shift in evolutionary pressures during domestication. Most characterized domestication events are associated with an extreme genetic bottleneck and alleviation of selective constraints in the original niche (10). These factors are predicted to increase the relative rate of nonsynonymous to synonymous (dN/dS) substitution, potentially resulting in the fixation of deleterious alleles (11). Previous studies comparing the distribution ...

“…In addition to affecting the rate of fixation of beneficial mutations, a deleterious mutation genetically linked to a beneficial mutation can "hitchhike" to high frequency or even fixation (36, 37). These theoretical predictions are beginning to be borne out in empirical data (38)(39)(40)(41)(42)(43)(44)(45)(46)(47).Despite the large body of work on hitchhiking and observations of recessive deleterious mutations in real organisms, there is a gap in our understanding of how recessive deleterious mutations affect adaptation. Models of hitchhiking have primarily focused on mutations with codominant effects, thus necessarily emphasizing the hitchhiking of weak deleterious mutations with stronger advantageous ones.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Obstruction of adaptation in diploids by recessive, strongly deleterious alleles

Assaf¹,

Petrov²,

Blundell

2015

Recessive deleterious mutations are common, causing many genetic disorders in humans and producing inbreeding depression in the majority of sexually reproducing diploids. The abundance of recessive deleterious mutations in natural populations suggests they are likely to be present on a chromosome when a new adaptive mutation occurs, yet the dynamics of recessive deleterious hitchhikers and their impact on adaptation remains poorly understood. Here we model how a recessive deleterious mutation impacts the fate of a genetically linked dominant beneficial mutation. The frequency trajectory of the adaptive mutation in this case is dramatically altered and results in what we have termed a "staggered sweep." It is named for its threephased trajectory: (i) Initially, the two linked mutations have a selective advantage while rare and will increase in frequency together, then (ii), at higher frequencies, the recessive hitchhiker is exposed to selection and can cause a balanced state via heterozygote advantage (the staggered phase), and (iii) finally, if recombination unlinks the two mutations, then the beneficial mutation can complete the sweep to fixation. Using both analytics and simulations, we show that strongly deleterious recessive mutations can substantially decrease the probability of fixation for nearby beneficial mutations, thus creating zones in the genome where adaptation is suppressed. These mutations can also significantly prolong the number of generations a beneficial mutation takes to sweep to fixation, and cause the genomic signature of selection to resemble that of soft or partial sweeps. We show that recessive deleterious variation could impact adaptation in humans and Drosophila.I n diploids, the fitness effect of having a single copy of a mutation depends not only on the mutation's selective effect, s, but also on its heterozygous effect, h. A fully recessive mutation (h = 0) is hidden in the heterozygote (hs = 0), and a fully dominant mutation (h = 1) is completely exposed (hs = s). Although it is generally agreed that beneficial mutations that reach fixation tend to be dominant (i.e., h ≥ 0.5) (1, 2), both empirical data and theoretical models (3-6) suggest that many strongly and even moderately deleterious mutations are likely to be recessive (i.e., h < 0.5). For example, studies of de novo mutations from both mutation accumulation and mutagenesis experiments in Drosophila melanogaster, Saccharomyces cerevisiae, and Caenorhabditis elegans have repeatedly found that strongly deleterious mutations tend to be completely recessive (h ≈ 0) and more weakly deleterious mutations tend to be partially recessive (h ≈ 0.1) (7-13). Furthermore, studies of natural populations have found that inbreeding depression is pervasive across sexually reproducing diploids and is mainly caused by recessive deleterious variation (reviewed in ref. 14). For example, in natural populations of Drosophila, approximately 30% of chromosomes carry a recessive lethal, and chromosomes that do not carry a recessive lethal suffer fro...