4.5 Article

Gene conversion: a non-Mendelian process integral to meiotic recombination

Journal

HEREDITY
Volume 129, Issue 1, Pages 56-63

Publisher

SPRINGERNATURE
DOI: 10.1038/s41437-022-00523-3

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Funding

  1. EASTBIO doctoral training partnership of the Biotechnology and Biological Sciences Research Council UK (BBSRC) [BB/M010996/1]

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Meiosis is the underlying mechanism of Mendelian genetics, involving a specialized cell division process to generate haploid gametes with shuffling and distribution of genetic material, leading to the restoration of diploid zygotes upon fertilization. Meiotic recombination, initiated by DNA double-strand breaks (DSBs), enables the physical connection and subsequent segregation of homologous chromosomes, which forms the basis of Mendelian laws. However, the repair mechanism of meiotic DSBs also leads to genetic distortions that result in non-Mendelian processes.
Meiosis is undoubtedly the mechanism that underpins Mendelian genetics. Meiosis is a specialised, reductional cell division which generates haploid gametes (reproductive cells) carrying a single chromosome complement from diploid progenitor cells harbouring two chromosome sets. Through this process, the hereditary material is shuffled and distributed into haploid gametes such that upon fertilisation, when two haploid gametes fuse, diploidy is restored in the zygote. During meiosis the transient physical connection of two homologous chromosomes (one originally inherited from each parent) each consisting of two sister chromatids and their subsequent segregation into four meiotic products (gametes), is what enables genetic marker assortment forming the core of Mendelian laws. The initiating events of meiotic recombination are DNA double-strand breaks (DSBs) which need to be repaired in a certain way to enable the homologous chromosomes to find each other. This is achieved by DSB ends searching for homologous repair templates and invading them. Ultimately, the repair of meiotic DSBs by homologous recombination physically connects homologous chromosomes through crossovers. These physical connections provided by crossovers enable faithful chromosome segregation. That being said, the DSB repair mechanism integral to meiotic recombination also produces genetic transmission distortions which manifest as postmeiotic segregation events and gene conversions. These processes are non-reciprocal genetic exchanges and thus non-Mendelian.

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