**13. Why is meiosis frequently associated with outcrossing?**

While the focus of this article is on the adaptive benefit of meiosis itself, we briefly consider why meiosis is frequently associated with outcrossing, where the chromosomes involved in recombination come from different unrelated parents in a prior generation. Previously, we discussed examples of meiosis occurring in association with inbreeding and self-fertilization. Meiosis with inbreeding will be favored when the costs of mating are high (e.g. the cost of finding a mate at low population density). These examples of inbred meiosis were presented to illustrate our argument that meiosis provides an adaptive advantage (accurate DNA repair) independent of whether significant recombinational variation is also produced. However, meiosis is often associated with outcrossing, and we now consider why.

A disadvantage of inbreeding, especially of self-fertilization, is expression of deleterious recessive mutations, resulting in inbreeding depression. Analysis of the effects of masking deleterious recessive mutations (genetic complementation) using heuristic modes and arguments indicated that complementation provides benefits sufficient to maintain

postulate that any segment containing a DSB will fail to complete its replication until the DSB is repaired. This limited and temporary blockage of replication may result directly from the break itself, or occur as a response to regulatory events set off by proteins that specifically bind to the broken ends. In any case, HRR can be carried out during the subsequent prophase I stage of meiosis, when the segment containing a DSB pairs with a non-sister homologue. This repair would then allow chromosome replication to be

**12. DNA damage during the mitotic divisions of the germ line in multicellular** 

In multicellular eukaryotes there are typically many mitoses during germ line development, and only a single final meiosis leading to gamete formation. During the mitotic cell divisions in the germ line, DSBs and other double-strand damages occurring after DNA replication are likely repaired by HRR or eliminated from the cell lineage by death and/or apoptosis of the damaged cell. We have argued above (section 11) that because of the lack of pairing of non-sister homologs during mitosis, HRR is unable to accurately repair double-strand damages occurring before replication. Thus when double-strand damages occur prior to replication during the mitotic divisions in the germ line the consequence will be either increased mutation or increased apoptosis. By analogy with the strategy used by somatic stem cells (section 11, above), we think that the preferred strategy during these mitotic divisions is likely to be apoptosis, since this avoids mutations in the germ line that could be passed on to progeny. However, double-strand damages occurring prior to replication during meiosis need not lead to apoptosis (which would likely decrease fecundity), since these can be accurately repaired by HRR between non-sister chromosomes. The consequence will be enhanced gamete viability and fecundity, that is, enhanced fitness. In the mitotic divisions of the germ-line prior to meiosis, loss of cells due to DNA damageinduced apoptosis need not be very costly to organism fitness, since such losses could be made up by extra cell divisions of undamaged cells. However, the loss of sperm or egg cells due to unrepaired DNA damage would likely have substantial costs to fitness due to loss of

fertility and progeny, as discussed above in section 5.

outcrossing, and we now consider why.

**13. Why is meiosis frequently associated with outcrossing?** 

While the focus of this article is on the adaptive benefit of meiosis itself, we briefly consider why meiosis is frequently associated with outcrossing, where the chromosomes involved in recombination come from different unrelated parents in a prior generation. Previously, we discussed examples of meiosis occurring in association with inbreeding and self-fertilization. Meiosis with inbreeding will be favored when the costs of mating are high (e.g. the cost of finding a mate at low population density). These examples of inbred meiosis were presented to illustrate our argument that meiosis provides an adaptive advantage (accurate DNA repair) independent of whether significant recombinational variation is also produced. However, meiosis is often associated with

A disadvantage of inbreeding, especially of self-fertilization, is expression of deleterious recessive mutations, resulting in inbreeding depression. Analysis of the effects of masking deleterious recessive mutations (genetic complementation) using heuristic modes and arguments indicated that complementation provides benefits sufficient to maintain

completed.

**organisms** 

outcrossing (H. Bernstein et al., 1985a, 1987; Michod, 1995). However, more explicit population genetic models have raised some issues that are in need of further clarification. In population genetics terms, the basic effect of outcrossing is to bring populations to Hardy-Weinberg (HW) equilibrium. Thus, outcrossing can be beneficial if there is another force that pushes the population away from HW equilibrium (generating either an excess or a deficit of heterozygotes) and if it's advantageous to go closer to HW equilibrium. One possible force that generates departure from HW equilibrium is dominance: for example if deleterious alleles tend to be recessive, after selection there will be an excess of heterozygotes (and a deficit of homozygotes). However in this case outcrossing is costly in the short term (because it tends to expose deleterious alleles), but beneficial in the long term (because purging them becomes more efficient). Otto (2003) showed that under this scenario high rates of outcrossing are favored only if deleterious alleles are weakly recessive (dominance close to 0.5). Another potential force pushing away from HW equilibrium considered by Roze and Michod (2010) is gene conversion which creates homozygosity. Gene conversion could result from mitotic HRR between sister chromosomes as discussed above. In this case (and if deleterious alleles tend to be partially recessive) outcrossing is beneficial in the short term (because it masks deleterious alleles) but disadvantageous in the long term (because purging is less efficient). The magnitude of this force may be estimated from rates of loss of heterozygosity during development [discussed in Roze and Michod (2010)]. The few estimates which exist indicate that the loss of heterozygosity is low, and thus this selective force for outcrossing may be weak. Clearly, we need more estimates of this critical parameter to know how large this force for outcrossing may be.

Another consequence of outcrossing is the generation of new genetic variants which may provide an additional long-term advantage.
