Muller's Ratchet and the Degeneration of Y Chromosomes: A Simulation Study

Engelstädter, Jan

doi:10.1534/genetics.108.092379

Cited by 49 publications

(55 citation statements)

References 43 publications

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“…The heterochromatic and gene-poor nature of the Y chromosome is consistent with theoretical models that predict rapid degeneration and specialization for male-specific functions of Y chromosomes in the absence of recombination (7)(8)(9). Furthermore, the hemizygous nature of the Y chromosome, combined with the lack of recombination, makes it uniquely susceptible to population genetic processes that reduce genetic variation and limit adaptation (10)(11)(12)(13).…”

supporting

confidence: 75%

Interspecific Y chromosome introgressions disrupt testis-specific gene expression and male reproductive phenotypes in Drosophila

Sackton

Montenegro

Hartl

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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The Drosophila Y chromosome is a degenerated, heterochromatic chromosome with few functional genes. Nonetheless, natural variation on the Y chromosome in Drosophila melanogaster has substantial trans-acting effects on the regulation of X-linked and autosomal genes. However, the contribution of Y chromosome divergence to gene expression divergence between species is unknown. In this study, we constructed a series of Y chromosome introgression lines, in which Y chromosomes from either Drosophila sechellia or Drosophila simulans are introgressed into a common D. simulans genetic background. Using these lines, we compared genome-wide gene expression and male reproductive phenotypes between heterospecific and conspecific Y chromosomes. We find significant differences in expression for 122 genes, or 2.84% of all genes analyzed. Genes down-regulated in males with heterospecific Y chromosomes are significantly biased toward testis-specific expression patterns. These same lines show reduced fecundity and sperm competitive ability. Taken together, these results imply a significant role for Y/X and Y/autosome interactions in maintaining proper expression of male-specific genes, either directly or via indirect effects on male reproductive tissue development or function.evolution | regulatory divergence | male fitness T he Y chromosome in Drosophila melanogaster comprises ∼40 MB of sequence (∼20% of the male genome), but contains fewer than 20 protein-coding genes, most of which are specialized male reproductive genes (1-5). The vast bulk of the chromosome is comprised of large blocks of repetitive sequences, including large microsatellite repeats, transposable element-derived sequence, and bobbed, the Y-linked rDNA array (6). The heterochromatic and gene-poor nature of the Y chromosome is consistent with theoretical models that predict rapid degeneration and specialization for male-specific functions of Y chromosomes in the absence of recombination (7-9). Furthermore, the hemizygous nature of the Y chromosome, combined with the lack of recombination, makes it uniquely susceptible to population genetic processes that reduce genetic variation and limit adaptation (10-13).As predicted by theory, little or no SNP polymorphism exists in single-copy protein-coding sequences on the Y chromosome (7, 14-16). However, several cytological forms of the Y chromosome segregate in at least some species of Drosophila (17), and molecular evidence also suggests that the Y chromosome is not monomorphic. Variation exists for the size of repetitive DNA blocks (18,19), and Y-linked genetic variation associates with variation in organismal phenotypes, including thermal tolerance of spermatogenesis (20, 21) and male mating success (22). Nonetheless, direct tests of association between variation at the rDNA locus and phenotypes reveal no significant effect (18) and theoretical predictions suggest that nonneutral variation on the Y chromosome can only be maintained under very restrictive conditions (23,24). We have previously shown that Y-linked gen...

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supporting

confidence: 75%

Interspecific Y chromosome introgressions disrupt testis-specific gene expression and male reproductive phenotypes in Drosophila

Sackton

Montenegro

Hartl

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition, Engelstädter (2008) showed that, in some circumstances, the presence of low-frequency deleterious mutations on X-linked homologs of the Y chromosome can greatly slow down the ratchet, compared with what is found in haploid simulations of the type used here.…”

Section: Plausibility Of the Modelmentioning

confidence: 59%

“…When U ¼ 1.89, the ratchet was stalled for short chromosomes (L ¼ 32 kb), but was going at a relative rate of 0.4% for L ¼ 1.28 Mb. As previously suggested (Bachtrog 2008b;Engelstädter 2008), the speed of the ratchet is likely to vary over different stages of Y chromosome degeneration: when the overall occurrence of major mutations is still high, interference among very strongly selected mutations alone leads to their fast accumulation, and the process is accelerated (about two-to fourfold) by the presence of BGS sites. With the erosion of genes from the neo-Y, U decreases and the ratchet slows down, but the effect of mutations at nonsynonymous sites starts to increase, until U becomes so low that the BGS effect cannot greatly increase the ratchet any longer (eventually the BGS effect will disappear as well).…”

Section: Discussionmentioning

confidence: 83%

Muller's Ratchet and the Degeneration of theDrosophila mirandaNeo-YChromosome

Kaiser

Charlesworth

2010

Genetics

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Since its formation about 1.75 million years ago, the Drosophila miranda neo-Y chromosome has undergone a rapid process of degeneration, having lost approximately half of the genes that it originally contained. Using estimates of mutation rates and selection coefficients for loss-of-function mutations, we show that the high rate of accumulation of these mutations can largely be explained by Muller's ratchet, the process of stochastic loss of the least-loaded mutational class from a finite, nonrecombining population. We show that selection at nonsynonymous coding sites can accelerate the process of gene loss and that this effect varies with the number of genes still present on the degenerating neo-Y chromosome.I N the absence of recombination, different sites in the genome do not evolve independently of each other (Fisher 1930;Muller 1932;Felsenstein 1974). As has been shown by studies of Drosophila populations, for example, this leads to reduced levels of nucleotide diversity (Bachtrog and Charlesworth 2002;Bartolomé and Charlesworth 2006) and to signatures of reduced adaptation at the DNA and protein sequence levels, such as lower optimal codon usage and an elevated rate of amino acid substitutions (Betancourt and Presgraves 2002;Bachtrog 2003Bachtrog , 2005Bartolomé and Charlesworth 2006;Betancourt et al. 2009). It is, however, still an open question how large-scale rearrangements and the loss of whole open reading frames can become fixed in nonrecombining regions of the genome, leading to the evolution of structures such as the small and degenerate Y chromosome of humans or the W chromosome of the chicken (Fridolfsson et al. 1998;Skaletsky et al. 2003).The neo-Y chromosome of Drosophila miranda is an example of a large nonrecombining region that is relatively young and has only partially degenerated (Steinemann and Steinemann 1998;Bartolomé and Charlesworth 2006;Bachtrog et al. 2008), enabling us to study the time frame over which degeneration can occur, as well as its possible causes. The neo-Y arose when an autosome (corresponding to chromosome arm 2R in D. melanogaster) became fused to the Y chromosome. This originally contained about 3000 genes with a total of about 4.3 Mb of coding sequence, based on the relative sizes of the euchromatic portions of the chromosome arms in the D. melanogaster genome (Adams et al. 2000) and the data in Clark et al. (2007), Table 2. Since there is no recombinational exchange between homologs in Drosophila males (Gethmann 1988), recombination between the neo-X and neo-Y became immediately restricted; within a short evolutionary time frame of approximately 1.75 million years , about half of the genes originally present on the neo-Y have lost their function (Bachtrog et al. 2008).To quantify the rate of accumulation of loss-offunction mutations on the neo-Y chromosome, which we denote by r, it is convenient to estimate the base-line rate of fixation for neutral mutations (which is equal to the mutation rate) and compare this to the observed rate of fixation of ''major'...

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“…First, to the extent that gene duplicates are fixed via positive selection, they are less likely to become fixed on nonrecombining relative to recombining chromosomes (Otto and Goldstein 1992;Clark 1994;Yong 1998;Otto and Yong 2002;Tanaka and Takahasi 2009). Second, regardless of whether Y-linked duplicates become fixed via genetic drift or by natural selection, the actions of Muller's ratchet, genetic hitchhiking, and background selection are expected to greatly increase the probability that Y-linked genes degenerate into nonfunctional pseudogenes Bachtrog 2006;Engelstadter 2008).…”

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confidence: 99%

Gene Duplication, Gene Conversion and the Evolution of the Y Chromosome

Connallon

Clark

2010

Genetics

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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.

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Muller's Ratchet and the Degeneration of Y Chromosomes: A Simulation Study

Cited by 49 publications

References 43 publications

Interspecific Y chromosome introgressions disrupt testis-specific gene expression and male reproductive phenotypes in Drosophila

Interspecific Y chromosome introgressions disrupt testis-specific gene expression and male reproductive phenotypes in Drosophila

Muller's Ratchet and the Degeneration of theDrosophila mirandaNeo-YChromosome

Gene Duplication, Gene Conversion and the Evolution of the Y Chromosome

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