Meiotic Error-Correction: How sexual reproduction may facilitate a trans-generational repair mechanism that can bias meiotic gene conversion against new mutations and in favor of ancestral alleles

Created on 28th June 2017

Virgil Reese;

Highly conserved DNA (where selection has most consistently punished variation) is comprised of elements of life’s code where mutations pose an especially highly risk. Thus, any difference between homologous chromosomes in these regions can warn of a potentially dangerous mutation; yet this warning is of little use to an organism, unless it can find some way to discern which of the two strands (paternal or maternal) harbors the mutation. Sexual reproduction may be addressing this challenge. If a sexual organism can just pass on to its offspring the suspicion that a particular DNA variant has a 50% chance of being a mutation, this offspring’s separately derived homologous chromosome can serve as both an independent check, and a correction template. This Meiotic Error-Correction process could work as follows - During the close association of homologous chromosomes in synapsis, primordial germ cells create a trans-generational epigenetic signature at (or near) an isolated DNA variant, thereby marking as ‘suspect’ both [mutant and normal] alleles. After fertilization, when one of these two ‘suspect-alleles’ is paired with a new homolog (in the subsequent meiosis) any persisting heterozygosity will again indicate a potential mutation; but now the marked suspect-allele can be recognized as the likely culprit. If this suspect-allele acts to promote meiotic homologous strand exchange, the ensuing mismatch can be resolved by gene conversion biased in favor of the less-suspect allele from the new chromosome, thus removing this mutation from the new organism’s germline.

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