Gene duplication, gene conversion and the evolution of the Y chromosome

Abstract

Nonrecombining chromosomes, such as the Y, are expected to degenerate over time due to reduced efficacy of natural selection compared to chromosomes that recombine. However, gene duplication, coupled with gene conversion between duplicate pairs, can potentially counteract forces of evolutionary decay that accompany asexual reproduction. Using a combination of analytical and computer simulation methods, we explicitly show that, although gene conversion has little impact on the probability that duplicates become fixed within a population, conversion can be effective at maintaining the functionality of Y-linked duplicates that have already become fixed. The coupling of Y-linked gene duplication and gene conversion between paralogs can also prove costly by increasing the rate of nonhomologous crossovers between duplicate pairs. Such crossovers can generate an abnormal Y chromosome, as was recently shown to reduce male fertility in humans. The results represent a step toward explaining some of the more peculiar attributes of the human Y as well as preliminary Y-linked sequence data from other mammals and Drosophila. The results may also be applicable to the recently observed pattern of tetraploidy and gene conversion in asexual, bdelloid rotifers.

Figure 1.—

Gene conversion can enhance the strength of positive selection for rare duplicate genes, whereas crossovers select against duplicates. Selection coefficient approximations (λ − 1) are based on the leading eigenvalue (Equation 1a), as described and justified in the text, and are presented as a ratio of selection with (d > 0) vs. without recombination (d = 0). Representative results are presented for u = 10⁻⁵ and assume that there is no gene conversion bias (i.e., b = 0.5).

Figure 2.—

The probability of fixation for Y-linked duplicate genes. The solid line depicts the analytical approximation from Equation 2. Circles represent the proportion of duplicate genotypes (out of 100,000 replicate simulations for each data point) that eventually become fixed within the population. Results are shown for d = 0, N = 1000, and u = 10⁻⁵, per locus, per generation. Values of d > 0 yield approximately the same results (see Figure S1).

Figure 3.—

Gene conversion increases the frequency of Y chromosome haplotypes that carry zero deleterious mutations (i.e., the “least-loaded” genotypic class). The cost of a mutation eliminating function of a copy of each duplicate pair is represented by sh (this cost increases from left to right on the x-axis). The relative proportion of mutation-free Y chromosomes in recombining vs. nonrecombining populations is presented as a ratio of the two scenarios (gene conversion increases the proportion of mutation-free Y's when this ratio is greater than one). The number of distinct, Y-linked genes is represented by n. Results are presented for c = 0, b = 0.5, and u = 5 × 10⁻⁴, per locus, per generation, and D = U = 2nu. Additional results are presented in Figure S3.

Figure 4.—

Intrapalindrome gene conversion prevents the erosion of Y chromosome gene content and enhances adaptation on the Y. N represents the Y-linked effective size, sh is the fitness cost associated with mutations to one copy of each duplicate pair, t refers to the generation within the simulation, and n is the number of distinct genes on the chromosome (including duplicates, each Y carries 2n genes). Results are presented for c = 0, b = 0.5, and u = 5 × 10⁻⁴, per locus, per generation. Each data point represents the average of 10 simulation replicates. Since estimates of gene conversion from human–chimp comparisons suggest that D may be considerably higher than the mutation rate (Rozen et al. 2003), the results, if anything, will underestimate the impact of gene conversion on functional gene retention.

Figure 5.—

The proportion of loss-of-function duplicates following 100,000 generations of mutation, selection, and genetic drift. Parameters are described in the Figure 4 legend and throughout the text. Results are presented for c = 0, b = 0.5, u = 5 × 10⁻⁴, per locus, per generation, and D on the order of the mutation rate, D = U = 2nu. Each point represents the average of 10 replicate simulations.