Live hot, die young: transmission distortion in recombination hotspots

Autor: Graham Coop, Simon Myers
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Cancer Research
Genome evolution
congenital
hereditary
and neonatal diseases and abnormalities
lcsh:QH426-470
Pan troglodytes
Population
genetic processes
Gene Conversion
information science
Biology
urologic and male genital diseases
Evolution
Molecular
03 medical and health sciences
0302 clinical medicine
Effective population size
Gene Frequency
Species Specificity
Chromosome Segregation
Homo (Human)
Hotspot (geology)
Genetics
Animals
Humans
DNA Breaks
Double-Stranded
Gene conversion
education
Molecular Biology
Genetics (clinical)
Ecology
Evolution
Behavior and Systematics
PRDM9
Alleles
030304 developmental biology
Recombination
Genetic
0303 health sciences
education.field_of_study
Evolutionary Biology
Models
Genetic
Human evolutionary genetics
Computational Biology
food and beverages
Genetics and Genomics
lcsh:Genetics
Genetics
Population
Evolutionary biology
Homologous recombination
030217 neurology & neurosurgery
Research Article
Zdroj: PLoS Genetics
PLoS Genetics, Vol 3, Iss 3, p e35 (2007)
DOI: 10.1371/journal.pgen.0030035
Popis: There is strong evidence that hotspots of meiotic recombination in humans are transient features of the genome. For example, hotspot locations are not shared between human and chimpanzee. Biased gene conversion in favor of alleles that locally disrupt hotspots is a possible explanation of the short lifespan of hotspots. We investigate the implications of such a bias on human hotspots and their evolution. Our results demonstrate that gene conversion bias is a sufficiently strong force to produce the observed lack of sharing of intense hotspots between species, although sharing may be much more common for weaker hotspots. We investigate models of how hotspots arise, and find that only models in which hotspot alleles do not initially experience drive are consistent with observations of rather hot hotspots in the human genome. Mutations acting against drive cannot successfully introduce such hotspots into the population, even if there is direct selection for higher recombination rates, such as to ensure correct segregation during meiosis. We explore the impact of hotspot alleles on patterns of haplotype variation, and show that such alleles mask their presence in population genetic data, making them difficult to detect.
Author Summary Recombination is a fundamental component of mammalian meiosis, required to help ensure that daughter cells receive the correct complement of chromosomes. This is highly important, as incorrect segregation causes miscarriage and disorders such as Down syndrome. In addition to its mechanistic function, recombination is also crucial in generating the genetic diversity on which natural selection acts. In humans and many other species, recombination events cluster into narrow hotspots within the genome. Given the vital role recombination plays in meiosis, we might expect that the positions of these hotspots would be tightly conserved over evolutionary time. However, there is now considerable evidence to the contrary; hotspots are not frozen in place, but instead evolve rapidly. For example, humans and chimpanzees do not share hotspot locations, despite their genomic sequences being almost 99% identical. The explanation for this may be, remarkably, that hotspots are the architects of their own destruction. The biological mechanism of recombination dooms them to rapid extinction by favoring the spread of hotspot-disrupting mutations. By mathematically modeling human hotspot evolution, we find that this mechanism can account for fast hotspot turnover, and in fact makes it very difficult for active hotspots to arise at all. Given that active hotspots do exist in our genome, newly arising hotspots must somehow be able to bypass their self-destructive tendency. Despite their importance, it is difficult to identify mutations that disrupt hotspots, as they hide their tracks in genetic data.
Databáze: OpenAIRE
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