Mutagenic Effect Of Insertions/Deletions In Chloroplast Genomes And Paralogs And The Molecular Mechanism Underlying Mutagenic Effect Of Insertions/Deletions

Mutations distribute non-uniformly across the whole genome and hotspots/cold-spots are common.But reasons for the variation of the mutation rate have not been fully understood.With huge amount of whole genome sequencing data was generated,the important evolutionary role of short insertions/deletions(indels)has been realized.Studies in eukaryotic genomes showed that more nucleotide substitutions distributed around indels and the hypothesis about the mutagenic effect of indels were proposed.And then,the mutagenic effect was further revealed in prokaryotic genomes.However,the underlying molecular mechanism has not been well understood.In this study,two parts of works were carried out to investigate the molecular mechanism of mutagenic effect of indels.First,mutagenic effect of indels was observed in organelle genomes as well as in comparison of paralogs.It demonstrated that mutagenic effect of indels is a universal rule.Second,evidences of recombination,especially biased gene conversion were discovered around indels in eukaryotic genomes.It supports our hypothesis that heterozygous state of indels introduced recombination and mutation rate was elevated in this process.Organelle genomes have special characters.It derived from bacteria and coevolved with nuclear genomes.No research focused on the mutagenic effect of indels in this special genome differing greatly from eukaryotic and prokaryotic nuclear genomes.Great amount of whole genome sequencing data online provides a great opportunity to address this problem.In this study,alignment and statistical analysis of 113 chloroplast genomes of plants revealed that mutagenic effect of indels was existed.And mutagenic pattern was consisted with that in eukaryotic and prokaryotic nuclear genomes.It demonstrated that mutagenic effect of indels is common in all kinds of genomic background.Previous studies were all based on the alignment between orthologs.The existence of mutagenic effect of indels in comparison between paralogs was uncertain.In this study,paralogs within 993 bacteria genomes belonging to 126 species were identified respectively.Alignment and statistical analysis revealed mutagenic effect of indels in paralogs although the effect intensity was weaker than that in orthologs.It demonstrated that mutagenic of indels caused by interaction between paralogs such as recombination is possible.And the mutagenic effect could be independent of chromosome pairing in meiosis.Molecular mechanism underlying mutagenic effect of indels has not been understood well.Several proposed hypotheses are controversial and more evidence is needed to support.In this study,we assumed that recombination was introduced by heterozygous state of indels and mutation rate was elevated by error-prone polymerases participated in this process.Results in analysis of population genome samples of model organism flies and Arabidopsis thaliana supported this hypothesis.Whole genome alignment showed that linkage disequilibrium between indel and around SNPs within 1Kb was drastically decreased with distance.It was strong evidence of frequent recombination events occurred in indel loci.Frequency spectrum of indels also showed evidence about biased gene conversion and alleles containing indels were favored.Comparison showed that insertions were more favored than deletions.So insertions diffused more rapidly in population and accumulated more nucleotide substitutions.It is much likely that recombination,especially biased gene conversion,is the molecular basis of mutagenic effect of indels.