Death of<i>PRDM9</i>coincides with stabilization of the recombination landscape in the dog genome

Axelsson, Erik; Webster, Matthew T.; Ratnakumar, Abhirami; Ponting, Chris P.; Lindblad‐Toh, Kerstin

doi:10.1101/gr.124123.111

Cited by 126 publications

(205 citation statements)

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“…The recombinational landscape of Western chimpanzees is also dominated by recombination hotspots (Auton et al 2012), as are those of mice (Smagulova et al 2011) and yeast (Mancera et al 2008). Intragenomic crossover rate heterogeneity is seen in dog genomes as well; although 80% of crossovers occur in 46% of the sequence, crossover rates fluctuate five orders of magnitude across the genome (Axelsson et al 2012).…”

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confidence: 97%

Fine-Scale Heterogeneity in Crossover Rate in thegarnet-scallopedRegion of theDrosophila melanogasterX Chromosome

et al. 2013

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Homologous recombination affects myriad aspects of genome evolution, from standing levels of nucleotide diversity to the efficacy of natural selection. Rates of crossing over show marked variability at all scales surveyed, including species-, population-, and individual-level differences. Even within genomes, crossovers are nonrandomly distributed in a wide diversity of taxa. Although intraand intergenomic heterogeneities in crossover distribution have been documented in Drosophila, the scale and degree of crossover rate heterogeneity remain unclear. In addition, the genetic features mediating this heterogeneity are unknown. Here we quantify finescale heterogeneity in crossover distribution in a 2.1-Mb region of the Drosophila melanogaster X chromosome by localizing crossover breakpoints in 2500 individuals, each containing a single crossover in this specific X chromosome region. We show 90-fold variation in rates of crossing over at a 5-kb scale, place this variation in the context of several aspects of genome evolution, and identify several genetic features associated with crossover rates. Our results shed new light on the scale and magnitude of crossover rate heterogeneity in D. melanogaster and highlight potential features mediating this heterogeneity.

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confidence: 97%

Fine-Scale Heterogeneity in Crossover Rate in thegarnet-scallopedRegion of theDrosophila melanogasterX Chromosome

et al. 2013

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“…Species that lack PRDM9, including dogs (Axelsson et al 2012), flies , Arabidopsis (Yelina et al 2012), and budding yeast , also exhibit patterns of fine-scale rate heterogeneity. C. elegans, which lacks functional PRDM9 (Oliver et al 2009), now joins the fission yeast Schizosaccharomyces pombe as a prominent exception.…”

Section: Elegans Crossover Distribution 143mentioning

confidence: 99%

Crossover Heterogeneity in the Absence of Hotspots inCaenorhabditis elegans

Kaur

Rockman

2014

Genetics

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Crossovers play mechanical roles in meiotic chromosome segregation, generate genetic diversity by producing new allelic combinations, and facilitate evolution by decoupling linked alleles. In almost every species studied to date, crossover distributions are dramatically nonuniform, differing among sexes and across genomes, with spatial variation in crossover rates on scales from whole chromosomes to subkilobase hotspots. To understand the regulatory forces dictating these heterogeneous distributions a crucial first step is the fine-scale characterization of crossover distributions. Here we define the wild-type distribution of crossovers along a region of the C. elegans chromosome II at unprecedented resolution, using recombinant chromosomes of 243 hermaphrodites and 226 males. We find that well-characterized large-scale domains, with little fine-scale rate heterogeneity, dominate this region's crossover landscape. Using the Gini coefficient as a summary statistic, we find that this region of the C. elegans genome has the least heterogeneous fine-scale crossover distribution yet observed among model organisms, and we show by simulation that the data are incompatible with a mammalian-type hotspot-rich landscape. The large-scale structural domains-the low-recombination center and the high-recombination arm-have a discrete boundary that we localize to a small region. This boundary coincides with the armcenter boundary defined both by nuclear-envelope attachment of DNA in somatic cells and GC content, consistent with proposals that these features of chromosome organization may be mechanical causes and evolutionary consequences of crossover recombination. MEIOTIC recombination creates novel combinations of parental alleles and is a powerful force shaping the genetic variation observed within a population. The frequency of recombination has a profound impact on the efficacy of natural selection in both purging deleterious mutations and in the formation of beneficial allelic combinations (Hill and Robertson 1966;Cutter and Payseur 2013). However, the intensity of recombination in different parts of a genome is rarely constant. Heterogeneity in the meiotic recombination rate has been observed across chromosome lengths and at finer scales of a few kilobase in diverse organisms.In Caenorhabditis elegans, meiotic recombination rates show a striking and reproducible chromosome-wide pattern of variation. Genetic maps of the five autosomes and X chromosome show that each has a low-recombination central domain flanked by high-recombination arm domains (Barnes et al. 1995;Rockman and Kruglyak 2009). This domain structure has dramatic effects on genetic variation and evolution (Cutter and Payseur 2003;Rockman et al. 2010;Andersen et al. 2012), but the underlying causes generating this pattern are not completely understood.The domain structure relates to unusual characteristics of the C. elegans chromosomes. The chromosomes lack localized centromeres and exhibit holocentric segregation during mitosis, with kinetochore pro...

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“…Regional aspects of chromatin structure play a role in this unusual control as PRDM9-independent and -dependent hotspots are intermixed in a gradient nearly 900 Kb long adjacent to the PAR. Support for the existence of an alternative mechanism comes from the observation that dogs, which lack a functional Prdm9 allele [12,13], nevertheless have recombination hotspots [13]. The existence of this alternative is driven by the need to overcome the paucity of DSBs relative to hotspots.…”

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confidence: 99%