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HUBER Christian

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26 Oct 2020
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Power and limits of selection genome scans on temporal data from a selfing population

Detecting loci under natural selection from temporal genomic data of selfing populations

Recommended by based on reviews by Christian Huber and 2 anonymous reviewers

The observed levels of genomic diversity in contemporary populations are the result of changes imposed by several evolutionary processes. Among them, natural selection is known to dramatically shape the genetic diversity of loci associated with phenotypes which affect the fitness of carriers. As such, many efforts have been dedicated towards developing methods to detect signatures of natural selection from genomes of contemporary samples [1].
Recent technological advances made the generation of large-scale genomic data from temporal samples, either from experimental populations or historical or ancient samples, accessible to a wide scientific community [2]. Notably, temporal population genomic data allow for a direct observation and study of how, for instance, allele frequencies change through time in response to evolutionary stimuli. Such information can be exploited to detect loci under natural selection, either via mathematical modelling or by investigating empirical distributions [3].
However, most of current methods to detect selection from temporal genomic data have largely ignored selfing populations, despite the latter comprising a significant proportion of species with social and economic importance. Selfing changes genomic patterns by reducing the effective recombination rate, which makes distinguishing between neutral evolution and natural selection even more challenging than for the case of outcrossing populations [4]. Nevertheless, an outlier-approach based on temporal genomic data for the selfing Arabidopsis thaliana population revealed loci under selection [5].
This study suggested the promise of detecting selection for selfing populations and encouraged further investigations to test the power of selection scans under different mating systems.
To address this question, Navascués et al. [6] extended a previously proposed approach for temporal genome scan [7] to incorporate partial self-fertilization. In the original implementation [7], it is assumed that, under neutrality, all loci provide levels of genetic differentiation drawn from the same distribution. If some of the loci are under selection, such distribution should show heterogeneity. Navascués et al. [6] proposed a test for the homogeneity between loci-specific and genome-wide differentiation by deriving a null distribution of FST via simulations using SLiM [8]. After filtering for low-frequency variants and correct for multiple tests, authors derived a statistical test for selection and assess its power under a wide range of scenarios of selfing rate, selection coefficient, duration and type of selection [6].
The newly proposed test achieved good performance to distinguish between neutral and selected loci in most tested scenarios.
As expected, the test's performance significantly drops for scenarios of high selfing rates and selection from standing variation. Additionally, the probability to correctly detect selection decreases with increasing distance from the causal variant. Intriguingly, the test showed high power when the selected ancestral allele had an initial low frequency, and when the selected derived allele had a high initial frequency. When applied to a data set of around 1,000 SNPs from the highly selfing Medicago truncatula population, an annual plant of the legume family [9], the test did not provide any candidate loci under selection [6].
In summary, the detection of loci under selection in selfing populations is and largely remains a challenging task even when explictly account for the different mating system. However, recombination events that occurred before the selective pressure allow ancestral beneficial alleles to exhibit a detectable pattern of non-neutrality. As such, in partially selfing populations, the strength of the footprint of selection depends on several factors, mostly on the selfing rate, the time of onset and type of selection.
One major assumption of this study is that the model implies unstructured population and continuity between samples obtained from the same geographical location over time. As such assumptions are typically violated in real populations, further research into the effect of more complex demographic scenarios is desired to fully understand the power to detect selection in selfing populations. Furthermore, more power could be gained by including additional genomic information at each time point. In this context, recent approaches that make full use of genomic data based on deep learning [10] may contribute significantly towards this goal. Similarly, the effect of data filtering on the power to detect selection should be further explored, especially in the context of DNA resequencing experiments. These analyses will help elucidate the power offered by selection scans from temporal genomic data in selfing populations.

References

[1] Stern AJ, Nielsen R (2019) Detecting Natural Selection. In: Handbook of Statistical Genomics , pp. 397–40. John Wiley and Sons, Ltd. https://doi.org/10.1002/9781119487845.ch14
[2] Leonardi M, Librado P, Der Sarkissian C, Schubert M, Alfarhan AH, Alquraishi SA, Al-Rasheid KAS, Gamba C, Willerslev E, Orlando L (2017) Evolutionary Patterns and Processes: Lessons from Ancient DNA. Systematic Biology, 66, e1–e29. https://doi.org/10.1093/sysbio/syw059
[3] Dehasque M, Ávila‐Arcos MC, Díez‐del‐Molino D, Fumagalli M, Guschanski K, Lorenzen ED, Malaspinas A-S, Marques‐Bonet T, Martin MD, Murray GGR, Papadopulos AST, Therkildsen NO, Wegmann D, Dalén L, Foote AD (2020) Inference of natural selection from ancient DNA. Evolution Letters, 4, 94–108. https://doi.org/10.1002/evl3.165
[4] Vitalis R, Couvet D (2001) Two-locus identity probabilities and identity disequilibrium in a partially selfing subdivided population. Genetics Research, 77, 67–81. https://doi.org/10.1017/S0016672300004833
[5] Frachon L, Libourel C, Villoutreix R, Carrère S, Glorieux C, Huard-Chauveau C, Navascués M, Gay L, Vitalis R, Baron E, Amsellem L, Bouchez O, Vidal M, Le Corre V, Roby D, Bergelson J, Roux F (2017) Intermediate degrees of synergistic pleiotropy drive adaptive evolution in ecological time. Nature Ecology and Evolution, 1, 1551–1561. https://doi.org/10.1038/s41559-017-0297-1
[6] Navascués M, Becheler A, Gay L, Ronfort J, Loridon K, Vitalis R (2020) Power and limits of selection genome scans on temporal data from a selfing population. bioRxiv, 2020.05.06.080895, ver. 4 peer-reviewed and recommended by PCI Evol Biol. https://doi.org/10.1101/2020.05.06.080895
[7] Goldringer I, Bataillon T (2004) On the Distribution of Temporal Variations in Allele Frequency: Consequences for the Estimation of Effective Population Size and the Detection of Loci Undergoing Selection. Genetics, 168, 563–568. https://doi.org/10.1534/genetics.103.025908
[8] Messer PW (2013) SLiM: Simulating Evolution with Selection and Linkage. Genetics, 194, 1037–1039. https://doi.org/10.1534/genetics.113.152181
[9] Siol M, Prosperi JM, Bonnin I, Ronfort J (2008) How multilocus genotypic pattern helps to understand the history of selfing populations: a case study in Medicago truncatula. Heredity, 100, 517–525. https://doi.org/10.1038/hdy.2008.5
[10] Sanchez T, Cury J, Charpiat G, Jay F Deep learning for population size history inference: Design, comparison and combination with approximate Bayesian computation. Molecular Ecology Resources, n/a. https://doi.org/10.1111/1755-0998.13224

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