The potential of shifting recombination hotspots to increase genetic gain in livestock breeding

Abstract

BackgroundThis study uses simulation to explore and quantify the potential effect of shifting recombination hotspots on genetic gain in livestock breeding programs.MethodsWe simulated three scenarios that differed in the locations of quantitative trait nucleotides (QTN) and recombination hotspots in the genome. In scenario 1, QTN were randomly distributed along the chromosomes and recombination was restricted to occur within specific genomic regions (i.e. recombination hotspots). In the other two scenarios, both QTN and recombination hotspots were located in specific regions, but differed in whether the QTN occurred outside of (scenario 2) or inside (scenario 3) recombination hotspots. We split each chromosome into 250, 500 or 1000 regions per chromosome of which 10% were recombination hotspots and/or contained QTN. The breeding program was run for 21 generations of selection, after which recombination hotspot regions were kept the same or were shifted to adjacent regions for a further 80 generations of selection. We evaluated the effect of shifting recombination hotspots on genetic gain, genetic variance and genic variance.ResultsOur results show that shifting recombination hotspots reduced the decline of genetic and genic variance by releasing standing allelic variation in the form of new allele combinations. This in turn resulted in larger increases in genetic gain. However, the benefit of shifting recombination hotspots for increased genetic gain was only observed when QTN were initially outside recombination hotspots. If QTN were initially inside recombination hotspots then shifting them decreased genetic gain.DiscussionShifting recombination hotspots to regions of the genome where recombination had not occurred for 21 generations of selection (i.e. recombination deserts) released more of the standing allelic variation available in each generation and thus increased genetic gain. However, whether and how much increase in genetic gain was achieved by shifting recombination hotspots depended on the distribution of QTN in the genome, the number of recombination hotspots and whether QTN were initially inside or outside recombination hotspots.ConclusionsOur findings show future scope for targeted modification of recombination hotspots e.g. through changes in zinc-finger motifs of the PRDM9 protein to increase genetic gain in production species.Electronic supplementary materialThe online version of this article (doi:10.1186/s12711-017-0330-5) contains supplementary material, which is available to authorized users.

Molecular evolution of the meiotic recombination pathway in mammals

“…; Gonen et al. ), and several features of the genomic landscape (Begun and Aquadro ; Charlesworth et al. ; Duret and Arndt ).…”

“…Meiotic recombination, the reciprocal exchange of DNA between homologous chromosomes, during meiosis is a major determinant of genetic diversity in populations, influencing the fate of new mutations (Hill and Robertson 1966), the efficacy of selection (Felsenstein 1974;Charlesworth et al 1993;Comeron et al 1999;Gonen et al 2017), and several features of the genomic landscape (Begun and Aquadro 1992;Charlesworth et al 1994;Duret and Arndt 2008). Recombination is also required for successful gametogenesis in most species that reproduce sexually (Hassold and Hunt 2001).…”

Interbreed variation in meiotic recombination rate and distribution in the domestic chicken <i>Gallus gallus</i>

“…We may speculate that the correspondence between recombination rate and breed's age appears to reflect a correspondence between recombination rate and genetic heterogeneity because genetic heterogeneity within each breed tends to decrease with time due to inbreeding and artificial selection (Lipinski et al, 2008;Gibbs et al, 2009). This hypothesis is consistent with the assumption that benefits of recombination (generation of new allele combinations) prevail over its costs (occurrence of deleterious mutations) as long as the population remains sufficiently heterogeneous (Kim and Stephan, 2000;Nachman, 2001;Ohta, 1999).…”

“…Recombination makes a substantial contribution to genetic and phenotypic variability. Therefore, the efficiency of natural and artificial selection is critically dependent on the recombination rate (Battagin et al, 2016;Gonen et al, 2017). It has been shown that populations with higher recombination rate demonstrate a stronger response to selection (Gorlov et al, 1992;Korol and Iliadi, 1994;Otto and Barton, 2001).…”

“…Therefore, the efficiency of natural and artificial selection is critically dependent on the recombination rate (Battagin et al, 2016;Gonen et al, 2017). It has been shown that populations with higher recombination rate demonstrate a stronger response to selection (Gorlov et al, 1992;Korol and Iliadi, 1994;Otto and Barton, 2001). Variation in recombination rate between species Payseur, 2008, 2011a;Smukowski and Noor, 2011) and individuals (Broman et al, 1998;Koehler et al, 2002) has been extensively studied in mammals but rather poorly in birds.…”