ReviewMale-driven evolution
Introduction
Almost 70 years ago, Haldane [1] proposed that the male mutation rate in humans is much higher than the female mutation rate because the male germline goes through many more rounds of cell divisions (DNA replications) per generation than does the female germline. Under this hypothesis, mutations arise mainly in males, so that evolution is ‘male-driven’ [2]. Although a higher mutation rate in males than in females has been well accepted, the magnitude of the male-to-female ratio (α) of mutation rate remains a point of contention. Knowing the magnitude of α is important because it is related to the issue of whether DNA replication errors are the major source of mutation 3., 4., which has been a subject of heated debate for the past several decades. Clearly, resolving these issues has implications for understanding the mechanism of mutagenesis and for the generation-time effect hypothesis, which postulates a faster molecular clock for organisms with a short generation time than for ones with a long generation time. In this article, we review studies on male-driven evolution in mammals and birds in the past decade and discuss factors that may affect the sex ratio of mutation rate. Note that mutation here refers to point (substitution) mutation; we are not concerned here with deletion or insertion mutation, which seem to have a mechanism of mutagenesis different from that of point mutation.
Section snippets
Estimating α from new or recently produced mutations
Dramatic advances in DNA technology have allowed the inference of the origin of a new or recently-produced mutation. When the origins of many mutations are inferred, α can be estimated as the ratio of the number of point mutations of paternal origin to that of maternal origin. This direct approach has replaced the indirect methods for estimating α from incidents of X-linked diseases [1]. Application of the direct approach to 119 families of haemophilia A (an X-linked recessive disease) led to
Evolutionary approach
In addition to the drawbacks mentioned above, the direct method may not be applicable to non-human organisms. As an alternative, Miyata et al. [2] proposed to estimate α from the mutation rates of the two sex chromosomes or of a sex chromosome and an autosome (or autosomes). Let Y, X, and A be the mutation rates for a Y-linked sequence, an X-linked sequence, and an autosomal sequence, respectively. Noting that in a population all Y-linked sequences are derived from the fathers, whereas
Methylation effects
In mammalian cells, DNA methylation occurs mostly at the C residue of CpG dinucleotides and a methylated C residue is easily transformed to a T through deamination, which creates a C→T transitional mutation. If the C→T transition occurs on the antisense strand of DNA, it is reflected as a G→A transition on the sense strand. As methylation occurs at a considerably higher rate in sperm DNA than in oocyte DNA [16], it increases the frequency of the paternal origin of mutation. For example, in Rett
Regional effects
The possibility that mutation rate may vary among genomic regions was first proposed, on the basis of very limited data, by Filipski [18] and Wolfe et al. [19]. Support for this hypothesis came from a study that detected substantial variation in both mutation rate and pattern among three primate arginosuccinate synthetase processed pseudogenes located in different regions of the genome [20]. Later, in a comparison of human and mouse genes, Matassi et al. [21] found that synonymous substitution
Conclusions and future directions
The above survey of studies that used the method of Miyata et al. [2] to estimate α suggests that it is between 5 and 6 for hominoids (humans and apes) (Table 2). The α value (∼11) estimated from the direct method (Table 1) was considerably higher for two reasons. First, it included the effect of methylation. Second, it referred to humans only; α is expected to be higher in humans than in apes because it increases with generation time. There is indeed a positive correlation between α and
Acknowledgements
This study was supported by grants from the National Institutes of Health.
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
References (60)
- et al.
Rates of nucleotide substitution in primates and rodents and the generation-time effect hypothesis
Mol Phyl Evol
(1996) - et al.
Sex biases in the mutation rate
Trends Genet
(1998) Why the rate of silent codon substitutions is variable within a vertebrate genome
J Theor Biol
(1988)- et al.
Chromosomal location effects on gene sequences evolution in mammals
Curr Biol
(1999) - et al.
Densities, length proportions, and other distributional features of repetitive sequences in the human genome estimated from 430 megabases of genomic sequence
Gene
(2000) - et al.
Genomewide comparison of DNA sequences between humans and chimpanzees
Am J Hum Genet
(2002) - et al.
Covariation of GC content and the silent site substitution rate in rodents: implications for methodology and for the evolution of isochores
Gene
(2000) - et al.
Human SNP variability and mutation rate are higher in regions of high recombination
Trends Genet
(2002) - et al.
Different base/base mispairs are corrected with different efficiencies and specificities in monkey kidney cells
Cell
(1988) - et al.
Higher rates of amino acid substitution in rodents than in humans
Mol Phylogenet Evol
(1992)
Brain Dysmeylinating Disease: Proteolipoprotein gene analysis in 82 patients with sporadic Pelizaeus-Merzbacher Disease: duplications, the major cause of the disease, originate more frequently in male germ cells, but point mutations do not. The Clinical European Network on Brain Dysmyelinating Disease
Am J Hum Genet
MECP2 mutations in sporadic cases of Rett syndrome are almost exclusively of paternal origin
Am J Hum Genet
Mutations in fibroblast growth-factor receptor 3 in sporadic cases of Achondroplasia occur exclusively on the paternally derived chromosome
Am J Hum Genet
Paternal origin of FGFR2 mutations in sporadic cases of Couzon syndrome and Pfeiffer syndrome
Am J Hum Genet
The rate of spontaneous mutation of a human gene
J Genet
Male-driven molecular evolution: a model and nucleotide sequence analysis
Cold Spring Harb Symp Quant Biol
Weak male-driven molecular evolution in rodents
Proc Natl Acad Sci USA
Direct and indirect estimation of the sex ratio of mutation frequencies in hemophilia A
Am J Hum Genet
Evidence for a selectively favourable reduction in the mutation rate of the X chromosome
Nature
Male-driven evolution of DNA sequences in birds
Nat Genet
Male-driven evolution among Eoaves? A test of the replicative division hypothesis in a heterogametic female (ZW) system
J Mol Evol
Male-driven evolution rates revealed from Z and W chromosome-linked ATP synthase α-subunit (ATP5A1) sequences in birds
J Mol Evol
Patterns of Y and X chromosome DNA sequence divergence during the Felidae radiation
Genetics
Comparison of substitution rates in ZFX and ZFY introns of sheep and goat related species supports the hypothesis of male-biased mutation rates
J Mol Evol
Unexpectedly similar rates of nucleotide substitution found in male and female hominids
Nature
Strong male-driven evolution of DNA sequences in humans and apes
Nature
Initial sequencing and analysis of the human genome
Nature
Epigenetic programming of differential gene expression in development and evolution
Dev Genet
Male-to-female ratios of mutation rate in higher primates estimated from intron sequences
Zool Studies
Mutation rates differ among regions of the mammalian genome
Nature
Cited by (175)
The first X-STR population study for the South African population
2024, Forensic Science International: ReportsRole of sperm DNA damage in creating de-novo mutations in human offspring: the ‘post-meiotic oocyte collusion’ hypothesis
2022, Reproductive BioMedicine OnlineCitation Excerpt :On the one hand, proponents of the disposable soma hypothesis hold up the male germ line as a remarkable model of genetic integrity. On the other hand, the male-driven evolution hypothesis (Li et al., 2002) sees the male germ line as the dominant source of genetic variation in humans, responsible for the vast majority of de-novo mutations and vulnerable to PAE mediated by a tendency to accumulate replication errors within the spermatogonial stem cell population. How can these two visions of the male germ line, as guardians of the genome on the one hand and the fountainhead of genetic variation on the other, be reconciled?
Phylogeny and sex chromosome evolution of Palaeognathae
2022, Journal of Genetics and GenomicsA reference database of forensic autosomal and gonosomal STR markers in the Tigray population of Ethiopia
2022, Forensic Science International: Genetics