Meiosis and beyond - understanding the mechanistic and evolutionary processes shaping the germline genome

Abstract

The separation of germ cell populations from the soma is part of the evolutionary transition to multicellularity. Only genetic information present in the germ cells will be inherited by future generations, and any molecular processes affecting the germline genome are therefore likely to be passed on. Despite its prevalence across taxonomic kingdoms, we are only starting to understand details of the underlying micro-evolutionary processes occurring at the germline genome level. These include segregation, recombination, mutation and selection and can occur at any stage during germline differentiation and mitotic germline proliferation to meiosis and post-meiotic gamete maturation. Selection acting on germ cells at any stage from the diploid germ cell to the haploid gametes may cause significant deviations from Mendelian inheritance and may be more widespread than previously assumed. The mechanisms that affect and potentially alter the genomic sequence and allele frequencies in the germline are pivotal to our understanding of heritability. With the rise of new sequencing technologies, we are now able to address some of these unanswered questions. In this review, we comment on the most recent developments in this field and identify current gaps in our knowledge.

Keywords: DNA repair; double-strand breaks; mutation hotspots; mutation rate; recombination; recombination hotspots; selection.

Fig 1

Illustration of genomic reconfiguration during spermatogenesis, and the processes that can lead to mutational outcomes. Prior to meiosis, chromatin is organised into topologically associated domains (TADs). These TADs are lost during prophase I, wherein the chromatin is separated more distinctly into active and inactive compartments despite its aggregation into a linear array of loops bound along a proteinaceous chromosome axis. Mobilisation of transposable elements (TEs) and endogenous retroviruses (ERVs), along with programmed recombination depending on the topoisomerase‐related enzyme, meiotic recombination protein SPO11 and nuclear division, provide opportunities for structural genomic changes via non‐allelic homologous recombination (NAHR) or non‐dysjunction, while the repair of DNA double‐strand breaks (DSBs) at the post‐meiotic stage also allows smaller indels and single nucleotide polymorphisms (SNPs) to arise via the non‐homologous end joining (NHEJ) pathway. Data from Alavattam et al. (2019), Patel et al. (2019) and Wang et al. (2019).