Synergistic epistasis of the deleterious effects of transposable elements

The replicative nature and generally deleterious effects of transposable elements (TEs) raise an outstanding question about how TE copy number is stably contained in host populations. Classic theoretical analyses predict that, when the decline in fitness due to each additional TE insertion is greater than linear, or when there is synergistic epistasis, selection against TEs can result in a stable equilibrium of TE copy number. While several mechanisms are predicted to yield synergistic deleterious effects of TEs, we lack empirical investigations of the presence of such epistatic interactions. Purifying selection with synergistic epistasis generates repulsion linkage between deleterious alleles. We investigated this population genetic signal in the likely ancestral Drosophila melanogaster population and found evidence supporting the presence of synergistic epistasis among TE insertions, especially TEs expected to exert large fitness impacts. Even though synergistic epistasis of TEs has been predicted to arise through ectopic recombination and TE-mediated epigenetic silencing mechanisms, we only found mixed support for the associated predictions. We observed signals of synergistic epistasis for a large number of TE families, which is consistent with the expectation that such epistatic interaction mainly happens among copies of the same family. Curiously, significant repulsion linkage was also found among TE insertions from different families, suggesting the possibility that synergism of TEs’ deleterious fitness effects could arise above the family level and through mechanisms similar to those of simple mutations. Our findings set the stage for investigating the prevalence and importance of epistatic interactions in the evolutionary dynamics of TEs.

Fine-scale haplotype structure reveals strong signatures of positive selection in a recombining bacterial pathogen

ABSTRACTIdentifying the forces that create and shape ecologically meaningful variation in bacteria remains an important challenge. For recombining bacteria, the sign and strength of linkage provide a unique lens into ongoing selection. We show derived alleles less than 300bp apart in Neisseria gonorrhoeae exhibit more coupling linkage than repulsion linkage, a pattern that cannot be explained by limited recombination or neutrality as these couplings are significantly stronger for nonsynonymous alleles compared to synonymous alleles. While linkage is shaped by many evolutionary processes, extensive simulations show only two distinct forms of positive selection can drive an excess of coupling linkage between neighboring nonsynonymous alleles: directional selection on introgressed alleles or selection that maintains distinct haplotypes in the presence of recombination. Our results establish a framework for identifying patterns of selection in fine-scale haplotype structure that indicate specific ecological processes in species that recombine with distantly related lineages or possess coexisting adaptive haplotypes.

Dissecting repulsion linkage in the dwarfing gene Dw3 region for sorghum plant height provides insights into heterosis

Heterosis is a main contributor to yield increase in many crop species. Different mechanisms have been proposed for heterosis: dominance, overdominance, epistasis, epigenetics, and protein metabolite changes. However, only limited examples of molecular dissection and validation of these mechanisms are available. Here, we present an example of discovery and validation of heterosis generated by a combination of repulsion linkage and dominance. Using a recombinant inbred line population, a separate quantitative trait locus (QTL) for plant height (qHT7.1) was identified near the genomic region harboring the known auxin transporter Dw3 gene. With two loci having repulsion linkage between two inbreds, heterosis in the hybrid can appear as a single locus with an overdominance mode of inheritance (i.e., pseudo-overdominance). Individually, alleles conferring taller plant height exhibited complete dominance over alleles conferring shorter height. Detailed analyses of different height components demonstrated that qHT7.1 affects both the upper and lower parts of the plant, whereas Dw3 affects only the part below the flag leaf. Computer simulations show that repulsion linkage could influence QTL detection and estimation of effect in segregating populations. Guided by findings in linkage mapping, a genome-wide association study of plant height with a sorghum diversity panel pinpointed genomic regions underlying the trait variation, including Dw1, Dw2, Dw3, Dw4, and qHT7.1. Multilocus mixed model analysis confirmed the advantage of complex trait dissection using an integrated approach. Besides identifying a specific genetic example of heterosis, our research indicated that integrated molecular dissection of complex traits in different population types can enable plant breeders to fine tune the breeding process for crop production.

Designing an optimal marker-based pedigree selection strategy for parent building in barley in the presence of repulsion linkage, using computer simulation

Pyramiding multiple desirable genes is an important method for the development of improved breeding materials and/or new cultivars. When the number of genes to be pyramided is many, or the genes are tightly linked in repulsion, it is practically impossible to recover the desirable recombinants in a single generation using a realistic population size, and repeated selection at several generations is required. The availability of markers tightly linked to the desirable genes makes it possible to conduct effective individual selection at early generations. This reduces the number of lines tested in the later generations and increases the desirable genotype frequency in the selected progeny. Computer simulation was used to develop such a marker-based pedigree selection strategy for the development of a barley line that contains 6 desired genes from 3 parental breeding lines (HS078 (H): 221222; PI366444 (P): 212222; Sloop Vic. (S): 122111; with 1 and 2 representing desirable and undesirable alleles, respectively), using the top cross H/P//S. The 6 genes targetted contribute to photoperiod sensitivity, Russian wheat aphid resistance, leaf rust resistance, boron tolerance, earliness per se, and cereal cyst nematode resistance. Under the assumption that perfect markers were available for all the 6 genes, a TC1 population of 300 plants was required to obtain 3 or more lines of the best genotype ‘211222/122111’, in which 3 loci were fixed for the desirable alleles, while the remaining 3 were kept as heterozygous. When single seed descent was used from the TC2 generation until complete homozygosity, the probability of obtaining lines of the desirable genotype (fixed for the desirable alleles at all 6 loci) was low due to the tight repulsion linkage between some of the genes. About 4000 individuals would be required to ensure with 99% probability the recovery of at least 1 line with the desirable genotype. The total number of lines that would need to be genotyped would be at least 5000. When the pedigree method was used in all test-cross generations, many schemes resulted in more lines of the fixed desirable genotype by genotyping fewer lines. The various options were compared using the genetic simulation software module QuLine, based on the QU-GENE simulation platform. The optimum scheme in terms of high success rate and relatively low genotyping costs consisted of the following steps: (1) in TC1 genotyping of 300 individuals allows for 3 or more individuals with the genotype ‘211222/122111’ to be identified; (2) in the TC2 individuals that are fixed for 3 loci and segregating for the remaining 3, loci can be selected from among 500 TC2 plants; (3) in the TC3, 50 or more individuals per TC3 line are genotyped for the 3 segregating loci, and individuals fixed for 5 loci and segregating for the 6th locus can be detected (genotyping is only needed for the segregating loci); (4) 25 individuals per TC4 line are genotyped for the single remaining segregating locus and several individuals of the desirable genotype (111111/111111) are finally selected. The desirable line is then obtained by collecting selfed seed from the selected TC4 plants. Using this scheme, on average, 320 desired TC5 lines were obtained by genotyping fewer than 2000 lines. When markers were tightly linked to the target genes but not diagnostic (perfect), not only was more genotyping required, but also appropriate phenotyping at the end of the marker selection process was necessary to confirm the presence of all the target genes. Under the assumption that recombination between marker and target gene was 5%, the best selection scheme identified, on average, 30 fixed desirable lines by genotyping 8000 lines and phenotyping 700 TC5 lines. If double haploid lines were produced from the F1 generation between H and P, and marker and phenotypic screening were conducted, followed by crossing of the individual with the target 2 loci in desired homozygous allelic status with parent S, the total amount of genotyping and phenotyping could be halved. This study showed that genetic simulation allows for numerous strategies to be compared using real data, and to develop an optimal crossing and selection strategy to combine desired alleles in the most effective and efficient way. This approach could likewise be used in other marker-assisted breeding programs.

Cytogenetic studies in wheat. XV. Location of rust resistance genes in VPM1 and their genetic linkage with other disease resistance genes in chromosome 2A

Inheritance studies showed that the VPM1-derived seedling resistances to stem rust, stripe rust, leaf rust, and powdery mildew were controlled by single genes; the genes for rust resistance were designated Sr38, Yr17, and Lr37, respectively, whereas the gene for resistance to powdery mildew was postulated to be Pm4b. Sr38, Yr17, and Lr37 were shown to be closely linked and distally located in the short arm of chromosome 2A. They showed very close repulsion linkage with Lr17 and were genetically independent of other genes known to be located in chromosome 2A. Previously unmapped, Yr1 appeared to be distally located in the long arm of chromosome 2A.Key words: stem rust, stripe rust, leaf rust, powdery mildew, monosomic analysis, telocentric mapping, genetic linkage.

Oat endosperm proteins associated with resistance to stem rust of oats

The presence of oat (Avena sativa L.) endosperm proteins, extracted with dimethylformamide mercaptoethanol – sodium dodecylsulfate and separated by dodecylsulfate polyacrylamide gel electrophoresis, was compared among cv. Rodney (carrying Pg4) and Rodney 0 derived backcross lines carrying single known genes Pg1, Pg2, Pg3, Pg8, Pg9, Pg13, Pg15, and Pg16, for stem rust resistance, and among other lines or cultivars with or without these genes. Most single-gene lines had polypeptide patterns similar to that of Rodney 0, a near-isogenic line with no known stem rust resistance. However, lines Rodney Pg3 and Rodney Pg9 were missing a 25.3-kDa avenin present in Rodney 0 and present in lines or cultivars that did not carry Pg9. The Rodney Pg13 line and several lines or cultivars that carried Pg13 were missing a 56.6-kDa polypeptide present in Rodney 0 and in several lines and cultivars that did not carry this gene. These results suggest that the Pg3/Pg9 and Pg13 loci were associated with the loci controlling the synthesis of the 25.3- and 56.6-kDa polypeptides, respectively. Results from genetic studies showed that gene Pg13 was linked in repulsion (linkage value 4.2 ± 1.9 cM) to the 56.6-kDa polypeptide locus.Key words: electrophoresis, oats, proteins, rust resistance.

Selection for recombination in a polygenic model – the mechanism

SummaryA polygenic model has been simulated in order to reveal the process whereby selection in an infinite population can lead to an increase in the frequency of alleles causing higher rates of recombination (CH alleles). Directional selection generates repulsion linkage disequilibrium (+ − + −), which is less strong in CH gametes (gametes carrying CH alleles). In consequence, CH gametes contribute greater phenotypic variability, and therefore respond more to directional selection: that is, they accumulate more selectively favoured alleles. CH alleles then increase in frequency by hitch-hiking. In contrast, normalizing selection, or frequent changes in the direction of selection, favour alleles for a low recombination rate.