Genetic Recombinationand Genome AdaptabilityGuillermo Palou Márquez | Supervised by Prof. Antonio Barbadilla Prados

Faculty of Biosciences

Bachelor’s degree in Genetics

2018

INTRODUCTION

The major roles of genetic recombination in the adaptability of a genome as a reasonable explanation forits advantage and evolution are:

❖ It produces the highest additive genetic variance possible, by constantly changing allele combinations.❖ It also maintains genetic variability in regions affected by linked selection after breaking down the LD.❖ Lastly, it increases the efficiency of selection in the different HRi scenarios by eroding the LD, increasing

the rate of adaptive substitutions and allowing a population to evolve at higher rate.

Thus, regardless of its origin, genetic recombination produces an advantage not only in sexualreproduction, but in mostly all living organisms, and it is likely to be explained from its central role shapingand adapting the nucleotide patterns along the genome.

RECOMBINATION AND GENETIC VARIABILITY

RECOMBINATION ENHANCES THE EFFICIENCY OF SELECTION: THE HILL-ROBERTSON EFFECT

Figure 2. Scatterplot between rate of recombination and (A)nucleotide diversity and (B) divergence. Adapted from [2].

Figure 4. Nucleotide diversity is (A) reduced bylinked selection or (B) maintained whenrecombination (red cross) is present aroundselected loci. Adapted from [4].

Figure 5. Different selective scenarios for the HRi. If norecombination is present, an interference appearsamong (A) favourable mutations (Selective sweeps),(B) deleterious mutations (Background Selection) or(C) weakly selected sites (Weak HRi effects). Whenrecombination is present, favourable alleles (green)are split from deleterious alleles (red) in differentchromosomes (blue), allowing selection to act moreefficiently, increasing or decreasing their frequency,respectively. Adapted from [6].

CONCLUSIONS

[1] Otto, S. P., and Barton, N. H. (1997). The evolution of recombination: Removing the limits to natural selection. Genetics, 147(2), 879–906.[2] Begun, D. J., and Aquadro, C. F. (1992). Levels of naturally occurring DNA polymorphism correlate with recombination rates in D. melanogaster. Nature, 356(6369), 519–520.[3] Scheinfeldt, L.B., and Tishkoff, S.A (2013). Recent human adaptation: genomic approaches, interpretation and insights. Nature Reviews Genetics, 14, 692-702.[4] Ellegren, H., and Galtier, N. (2016). Determinants of genetic diversity. Nature Reviews Genetics, 17(7), 422–433. [5] Hill, W. G., and Robertson, A. (1966). The effect of linkage on limits to artificial selection. Genetics Research, 8, 269–294.[6] Casillas, S., and Barbadilla, A. (2017). Molecular population genetics. Genetics, 205(3), 1003–1035. [7] Mackay, T. F. C., et al. (2012). The Drosophila melanogaster Genetic Reference Panel. Nature, 482(7384), 173–178.[8] Castellano, D., et al. (2016). Adaptive evolution is substantially impeded by Hill-Robertson interference in drosophila. Molecular Biology and Evolution, 33(2), 442–455.

LITERATURE CITED

A

A

Figure 1. Basic scheme of genetic recombination. A pair of homologous chromosomes exchange reciprocallygenetic information by breakage and reunion of two chromatids, creating new allele compositions.

A positive correlation between rate of recombinationand nucleotide diversity was found (Fig. 2A) [2]. H0:recombination is mutagenic, and more mutation rate(µ) implies more divergence (K). H1: Mutation is notthe cause. No correlation between divergence and rateof recombination was found (Fig. 2B), rejecting H0.

1 2 The explanation for the correlation was attributed to linked selection, where linkagedisequilibrium (LD) is generated between a selected allele and neutral variation fromaround: Selected alleles either from selective sweep (Fig. 3A) or background selection(Fig. 3B) hitchhikes all tightly linked neutral variation to fixation or loss, respectively,reducing the levels of nucleotide diversity (Fig. 4A).

Figure 3. Neutral variation (circles) is reduced in (A) selective sweep by favourable mutations(stars) or (B) background selection by deleterious mutations (red circles). Adapted from [3].

3 LD generated by linked selection is brokendown by recombination, avoiding thereduction in neutral variability, and themaintenance of high diversity levels (Fig. 4B).

B

If there are multiple genetic variantssimultaneously selected, and they are mutually inLD, an interference among them will appear [5].This is known as Hill-Robertson interference(HRi). Recombination, by breaking down the LD,can relieve the selected variants from theinterference and expose them more efficiently toselection. Different selective scenarios exemplifyHRi (Fig. 5). As a consequence, the rate ofadaptive fixation increases as recombinationincreases, which allows a population to evolve athigher rate [6].

The initial linear relationship between recombination and adaptation reaches anasymptote at a recombination rate of ~2 cM/Mb (Fig. 6) [7]. This value can be interpretedas the rate of adaptive evolution that would occur if there was no HRi. Therefore, thereexists an optimal value of recombination (Ropt) for the adaptation rate of a genome. UsingRopt, HRi was estimated to reduce the evolutionary adaptation rate by ~27% (shaded areain Fig. 6) in the D. melanogaster genome [8], which is a highly significant value.

Figure 6. Relationship betweenadaptation rate and recombinationrate. An asymptotic value is reached ata recombination rate of 2 cM/Mb(Ropt), where alleles are free from HRi.Figure from [6].

Genetic recombination is a process practically universal in all living organisms, raising the question for itsevolutionary predominance. In eukaryotes, recombination occurs mainly in meiosis during the pairing ofhomologous chromosomes, which reshuffles the genetic material between two chromatids (Fig. 1). There aretwo main hypothesis for the advantage of recombination [1]: (1) It plays a mechanistical role in the cell cycle(physiological hypothesis) and (2) it generates variation that may be beneficial when facing adaptivechallenges (evolutionary hypothesis). In the present work, I explore the second hypothesis, considering therole of recombination in generating and maintaining genetic variability at the nucleotide level, and trying toelucidate the conditions under which this variability generating process is selected favourably.

4 5

B