The power of randomization by sex in multilocus genetic evolution

Background Many hypotheses have been proposed for how sexual reproduction may facilitate an increase in the population mean fitness, such as the Fisher-Muller theory, Muller’s ratchet and others. According to the recently proposed mixability theory, however, sexual recombination shifts the focus of natural selection away from favoring particular genetic combinations of high fitness towards favoring alleles that perform well across different genetic combinations. Mixability theory shows that, in finite populations, because sex essentially randomizes genetic combinations, if one allele performs better than another across the existing combinations of alleles, that allele will likely also perform better overall across a vast space of untested potential genotypes. However, this superiority has been established only for a single-locus diploid model. Results We show that, in both haploids and diploids, the power of randomization by sex extends to the multilocus case, and becomes substantially stronger with increasing numbers of loci. In addition, we make an explicit comparison between the sexual and asexual cases, showing that sexual recombination is the cause of the randomization effect. Conclusions That the randomization effect applies to the multilocus case and becomes stronger with increasing numbers of loci suggests that it holds under realistic conditions. One may expect, therefore, that in nature the ability of an allele to perform well in interaction with existing genetic combinations is indicative of how well it will perform in a far larger space of potential combinations that have not yet materialized and been tested. Randomization plays a similar role in a statistical test, where it allows one to draw an inference from the outcome of the test in a small sample about its expected outcome in a larger space of possibilities—i.e., to generalize. Our results are relevant to recent theories examining evolution as a learning process. Reviewers This article was reviewed by David Ardell and Brian Golding.

Variance and limiting distribution of coalescence times in a diploid model of a consanguineous population

Recent modeling studies interested in runs of homozygosity (ROH) and identity by descent (IBD) have sought to connect these properties of genomic sharing to pairwise coalescence times. Here, we examine a variety of features of pairwise coalescence times in models that consider consanguinity. In particular, we extend a recent diploid analysis of mean coalescence times for lineage pairs within and between individuals in a consanguineous population to derive the variance of coalescence times, studying its dependence on the frequency of consanguinity and the kinship coefficient of consanguineous relationships. We also introduce a separation-of-time-scales approach that treats consanguinity models analogously to mathematically similar phenomena such as partial selfing, using this approach to obtain coalescence-time distributions. This approach shows that the consanguinity model behaves similarly to a standard coalescent, scaling population size by a factor 1 − 3c, where c represents the kinship coefficient of a randomly chosen mating pair. It provides the explanation for an earlier result describing mean coalescence time in the consanguinity model in terms of c. The results extend the potential to make predictions about ROH and IBD in relation to demographic parameters of diploid populations.

A universal vector concept for a direct genotyping of transgenic organisms and a systematic creation of homozygous lines

Diploid transgenic organisms are either hemi- or homozygous. Genetic assays are, therefore, required to identify the genotype. Our AGameOfClones vector concept uses two clearly distinguishable transformation markers embedded in interweaved, but incompatible Lox site pairs. Cre-mediated recombination leads to hemizygous individuals that carry only one marker. In the following generation, heterozygous descendants are identified by the presence of both markers and produce homozygous progeny that are selected by the lack of one marker. We prove our concept in Tribolium castaneum by systematically creating multiple functional homozygous transgenic lines suitable for long-term fluorescence live imaging. Our approach saves resources and simplifies transgenic organism handling. Since the concept relies on the universal Cre-Lox system, it is expected to work in all diploid model organisms, for example, insects, zebrafish, rodents and plants. With appropriate adaptions, it can be used in knock-out assays to preselect homozygous individuals and thus minimize the number of wasted animals.

Powerful decomposition of complex traits in a diploid model using Phased Outbred Lines

Explaining trait differences between individuals is a core but challenging aim of life sciences. Here, we introduce a powerful framework for complete decomposition of trait variation into its underlying genetic causes in diploid model organisms. We intercross two natural genomes over many sexual generations, sequence and systematically pair the recombinant gametes into a large array of diploid hybrids with fully assembled and phased genomes, termed Phased Outbred Lines (POLs). We demonstrate the capacity of the framework by partitioning fitness traits of 7310 yeast POLs across many environments, achieving near complete trait heritability (mean H2 = 91%) and precisely estimating additive (74%), dominance (8%), second (9%) and third (1.8%) order epistasis components. We found nonadditive quantitative trait loci (QTLs) to outnumber (3:1) but to be weaker than additive loci; dominant contributions to heterosis to outnumber overdominant (3:1); and pleiotropy to be the rule rather than the exception. The POL approach presented here offers the most complete decomposition of diploid traits to date and can be adapted to most model organisms.