Chromosome size affects sequence divergence between species through the interplay of recombination and selection

Abstract

The structure of the genome shapes the distribution of genetic diversity and sequence divergence. To investigate how the relationship between chromosome size and recombination rate affects sequence divergence between species, we combined empirical analyses and evolutionary simulations. We estimated pairwise sequence divergence among 15 species from three different mammalian clades-Peromyscus rodents, Mus mice, and great apes-from chromosome-level genome assemblies. We found a strong significant negative correlation between chromosome size and sequence divergence in all species comparisons within the Peromyscus and great apes clades but not the Mus clade, suggesting that the dramatic chromosomal rearrangements among Mus species may have masked the ancestral genomic landscape of divergence in many comparisons. Our evolutionary simulations showed that the main factor determining differences in divergence among chromosomes of different sizes is the interplay of recombination rate and selection, with greater variation in larger populations than in smaller ones. In ancestral populations, shorter chromosomes harbor greater nucleotide diversity. As ancestral populations diverge, diversity present at the onset of the split contributes to greater sequence divergence in shorter chromosomes among daughter species. The combination of empirical data and evolutionary simulations revealed that chromosomal rearrangements, demography, and divergence times may also affect the relationship between chromosome size and divergence, thus deepening our understanding of the role of genome structure in the evolution of species divergence.

Keywords: Mus; Peromyscus; genome assembly; genome evolution; great apes; mammal.

Figure 1

Plots showing the relationship between log₁₀‐transformed chromosome size (bp) and sequence divergence among species within the Peromyscus, Hominidae and Mus clades. In the left panel (A, C, E), one representative comparison from each of the Peromyscus, Hominidae, and Mus clades is displayed (see Figures S2, S3, and S4 for all comparisons). The comparison of the same species pairs is represented in the right panel, but the query and reference species are inverted in plots (B), (D), and (F) to highlight that in the Mus, but not in the Peromyscus and Hominidae clades, the choice of the reference genome affects the correlation between chromosome size and d. In the bottom panel, the comparison between Mus spretus and M. pahari is shown, with M. pahari as a reference on the left (E) and with M. spretus as a reference on the right (F).

Figure 2

Boxplots summarizing results from evolutionary simulations on the relationship between recombination rate and π after 20N_e generations in the ancestral population (panel A on the left) and d one generation after the split after a mild bottleneck (0.5 of ancestral N_e ) between the two daughter populations (panel B on the right) in each of three simulated ancestral N_e . Boxplots refer to the results from the models with selection, and the dashed line shows the results from the neutral models. Here are the results with models without gene conversion, as no significant differences were found between models with and without gene conversion.

Figure 3

Boxplots summarizing results from evolutionary simulations on the relationship between recombination rate and d in models with selection and without gene conversion in each of three simulated ancestral N_e and three time points after the split from the ancestral pop_A and a mild bottleneck. Gene conversion was not included in these models, as no significant differences were found between models with and without gene conversion. (See Fig. S5 for comparisons with neutral models and models with a more severe bottleneck).

Figure 4

Plots showing the decay of Δd over time in the evolutionary simulations based on the models with and without gene conversion and with a mild (0.5) and a severe bottleneck (0.1) for each of the three simulated ancestral N_e .