Late Replicating Domains Are Highly Recombining in Females but Have Low Male Recombination Rates: Implications for Isochore Evolution

Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
PLoS ONE (Impact Factor: 3.23). 09/2011; 6(9):e24480. DOI: 10.1371/journal.pone.0024480
Source: PubMed


In mammals sequences that are either late replicating or highly recombining have high rates of evolution at putatively neutral sites. As early replicating domains and highly recombining domains both tend to be GC rich we a priori expect these two variables to covary. If so, the relative contribution of either of these variables to the local neutral substitution rate might have been wrongly estimated owing to covariance with the other. Against our expectations, we find that sex-averaged recombination rates show little or no correlation with replication timing, suggesting that they are independent determinants of substitution rates. However, this result masks significant sex-specific complexity: late replicating domains tend to have high recombination rates in females but low recombination rates in males. That these trends are antagonistic explains why sex-averaged recombination is not correlated with replication timing. This unexpected result has several important implications. First, although both male and female recombination rates covary significantly with intronic substitution rates, the magnitude of this correlation is moderately underestimated for male recombination and slightly overestimated for female recombination, owing to covariance with replicating timing. Second, the result could explain why male recombination is strongly correlated with GC content but female recombination is not. If to explain the correlation between GC content and replication timing we suppose that late replication forces reduced GC content, then GC promotion by biased gene conversion during female recombination is partly countered by the antagonistic effect of later replicating sequence tending increase AT content. Indeed, the strength of the correlation between female recombination rate and local GC content is more than doubled by control for replication timing. Our results underpin the need to consider sex-specific recombination rates and potential covariates in analysis of GC content and rates of evolution.

14 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There is considerable variation within eukaryotic genomes in the local rate of crossing over. Why is this and what effect does it have on genome evolution? On the genome scale, it is known that by shuffling alleles, recombination increases the efficacy of selection. By contrast, the extent to which differences in the recombination rate modulate the efficacy of selection between genomic regions is unclear. Recombination also has direct consequences on the origin and fate of mutations: biased gene conversion and other forms of meiotic drive promote the fixation of mutations in a similar way to selection, and recombination itself may be mutagenic. Consideration of both the direct and indirect effects of recombination is necessary to understand why its rate is so variable and for correct interpretation of patterns of genome evolution.
    Trends in Genetics 12/2011; 28(3):101-9. DOI:10.1016/j.tig.2011.11.002 · 9.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite the rapid increase of size in phylogenomic datasets, a number of important nodes on animal phylogeny are still unresolved. Among these, the rooting of the placental mammal tree is still a controversial issue. One difficulty lies in the pervasive phylogenetic conflicts among genes, with each one telling its own story, which may be reliable or not. Here we identified a simple criterion, i.e. the GC-content, which substantially helps in determining which gene trees best reflect the species tree. We assessed the ability of 13 111 coding sequence alignments to correctly reconstruct the placental phylogeny. We found that GC-rich genes induced a higher amount of conflict among gene trees, and performed worse than AT-rich genes in retrieving well-supported, consensual nodes on the placental tree. We interpret this GC-effect mainly as a consequence of genome-wide variations in recombination rate. Indeed, recombination is known to drive GC-content evolution through GC-biased gene conversion, and might be problematic for phylogenetic reconstruction, for instance in an incomplete lineage sorting context. When we focused on the AT-richest fraction of the dataset, the resolution level of the placental phylogeny was greatly increased, and a strong support was obtained in favor of an Afrotheria rooting, i.e. Afrotheria as the sister group of all other placentals. We show that in mammals most conflicts among gene trees, which have so far hampered the resolution of the placental tree, are concentrated in the GC-rich regions of the genome. We argue that the GC-content - since it is a reliable indicator of the long-term recombination rate - is an informative criterion that could help in identifying the most reliable molecular markers for species tree inference.
    Molecular Biology and Evolution 06/2013; 30(9). DOI:10.1093/molbev/mst116 · 9.11 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Evolution of mammalian reproductive success has witnessed a strong dependence on maternal resources through placental in utero development. Genomic imprinting, which has an active role in mammalian viviparity, also reveals a biased role for matrilineal DNA in its regulation. The co-existence of three matrilineal generations as one (mother, foetus and post-meiotic oocytes) has provided a maternal niche for transgenerational co-adaptive selection pressures to operate. In utero foetal growth has required increased maternal feeding in advance of foetal energetic demands; the mammary glands are primed for milk production in advance of birth, while the maternal hypothalamus is hormonally primed by the foetal placenta for nest building and post-natal care. Such biological forward planning resulted from maternal-foetal co-adaptation facilitated by co-expression of the same imprinted allele in the developing hypothalamus and placenta. This co-expression is concurrent with the placenta interacting with the adult maternal hypothalamus thereby providing a transgenerational template on which selection pressures may operate ensuring optimal maternalism in this and the next generation. Invasive placentation has further required the maternal immune system to adapt and positively respond to the foetal allotype. Pivotal to these mammalian evolutionary developments, genomic imprinting emerged as a monoallelic gene dosage regulatory mechanism of tightly interconnected gene networks providing developmental genetic stability for in utero development.Heredity advance online publication, 26 February 2014; doi:10.1038/hdy.2014.8.
    Heredity 02/2014; 113(2). DOI:10.1038/hdy.2014.8 · 3.81 Impact Factor
Show more

Preview (3 Sources)

14 Reads
Available from