Meiotic recombination counteracts male-biased mutation (male-driven evolution)

Abstract

Meiotic recombination is believed to produce greater genetic variation despite the fact that deoxyribonucleic acid (DNA)-replication errors are a major source of mutations. In some vertebrates, mutation rates are higher in males than in females, which developed the theory of male-driven evolution (male-biased mutation). However, there is little molecular evidence regarding the relationships between meiotic recombination and male-biased mutation. Here we tested the theory using the frog Rana rugosa, which has both XX/XY- and ZZ/ZW-type sex-determining systems within the species. The male-to-female mutation-rate ratio (α) was calculated from homologous sequences on the X/Y or Z/W sex chromosomes, which supported male-driven evolution. Surprisingly, each α value was notably higher in the XX/XY-type group than in the ZZ/ZW-type group, although α should have similar values within a species. Interestingly, meiotic recombination between homologous chromosomes did not occur except at terminal regions in males of this species. Then, by subdividing α into two new factors, a replication-based male-to-female mutation-rate ratio (β) and a meiotic recombination-based XX-to-XY/ZZ-to-ZW mutation-rate ratio (γ), we constructed a formula describing the relationship among a nucleotide-substitution rate and the two factors, β and γ. Intriguingly, the β- and γ-values were larger and smaller than 1, respectively, indicating that meiotic recombination might reduce male-biased mutations.

Keywords: germ cell; male-biased mutation; male-driven evolution; meiotic recombination; mutation rate; sex chromosome.

Figure 1.

Phylogenetic tree analyses based on mitochondrial nucleotide sequences of four genetic groups in Rana rugosa. (a) The distribution of five R. rugosa genetic groups in Japan [7]. Specimens were collected from Sekigahara (1) and Hamamatsu (2) for the XY group, and from Kanazawa (3) and Niigata (4) for the ZW group. The black and blue/green bent lines represent big mountain ranges and large rivers, respectively. (b) The evolutionary scenario of the X/Y and Z/W sex chromosomes. An inversion on the ancestral chromosome 7 led to chromosome 7 in the Western Japan group, which was the original type of Z and Y sex chromosomes. Another inversion on chromosome 7 in Eastern Japan formed the original type of W and X sex chromosomes. The hybridization between the ancestors of the Western Japan and Eastern Japan groups produced the XY and ZW groups. (c) The maximum likelihood (ML) phylogenetic tree based on nucleotide sequences of the mitochondrial 12S and 16S rRNA genes. Bufo japonicus was used as an outgroup. A best-fit nucleotide-substitution model was selected by model selection. The same topology was obtained using neighbour-joining (NJ) and maximum-parsimony (MP) analyses. Numerals at each node denote the NJ/ML/MP bootstrap percentage values of 1 000 replications. (d) A time-calibrated ML phylogenetic tree based on the nucleotide sequences of the mitochondrial 12S and 16S rRNA genes. To calibrate the molecular clock, the divergence time between R. bedriagae and R. cretensis was fixed at 5 million years ago (Ma). White box, 95% confidence interval; black diamond, calibration point.

Figure 2.

Restricted pairing of homologous chromosomes in the XY and ZZ males of Rana rugosa. Chromosomes at meiotic metaphase I were prepared using mature Hamamatsu and Mutsu males from the XY and ZW groups, respectively, and were stained with Giemsa. A representative among 18 or 33 pictures of a male from the Hamamatsu or Mutsu population, respectively, are shown. Note that there was no pairing between homologous chromosomes except at terminal regions in all the pictures. An arrow indicates an X−Y sex chromosome pair. Scale bar, 10 µm. (Online version in colour.)

Figure 3.

Conventional and modified formulae for male-driven evolution and/or recombination in XX/XY and ZZ/ZW systems. (Online version in colour.)