Human mutation—blame (mostly) men

Ellegren, Hans

doi:10.1038/ng0502-9

Cited by 16 publications

(7 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Instead the main concern in previous reviews has been to discuss the theory, issues surrounding the estimation of a, and explain contradictory results. (7)(8)(9)(10)16) In part, the bias in the literature towards gonochorists and male-driven evolution must result from the fact that we have viewed species predominantly as having separate sexes. The reality is somewhat different, however.…”

Section: Introductionmentioning

confidence: 98%

“…Although it took around 65 years, (3)(4)(5)(6) it is now beyond doubt that the accumulated mutation frequency in some male germlines is elevated compared with females. (4,7,8) The debate now tends to be more concerned with the magnitude of the effect (represented by a, the ratio of mutations originating in males compared to females (7) ), and whether the causes of variation between estimates are real or due to ascertainment bias. (4,7,(9)(10)(11)(12) The basic rationale behind the argument for male-driven evolution is simple.…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

The ovotestis: an underdeveloped organ of evolution

Davison

2006

BioEssays

View full text Add to dashboard Cite

In animals that have separate sexes (gonochorists), many sperm are produced to fertilise a few eggs. As the male germline undergoes more mitoses, so the accumulated mutation frequency is elevated in sperm compared with ova, and evolution is 'male-driven'. In contrast, in many hermaphroditic animals, a single organ--the ovotestis--produces both ova and sperm. Since self-renewing cells in the ovotestis may give rise to both cell types throughout life, ova in hermaphrodites could in theory have undergone as many cell divisions as sperm. Here, I consider some possible effects of the ovotestis on evolution. In particular, I hypothesise that the accumulated mutation frequency of nuclear genes in hermaphrodites (including species that change sex) may reach twice that compared with gonochorists. There may be an even greater increase in the mitochondrial mutation frequency. Further developmental studies and the accumulation of comparative data should allow hypothesis testing. If the prediction is correct, then it may provide the most-straightforward explanation for the extraordinary diversity of mitochondrial DNA in some hermaphrodites, especially molluscs.

show abstract

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 98%

The ovotestis: an underdeveloped organ of evolution

Davison

2006

BioEssays

View full text Add to dashboard Cite

show abstract

“…Many factors might be important for the mutational processes in microsatellites, such as e.g. allele size, motif size, gender, and G/C content [8-15]. Mutation patterns may also depend on the genomic context such as the particular location on a chromosome and functional potential of the transcribed product [9,16-18], as well as the effectiveness of mismatch repair enzymes [19,20].…”

Section: Introductionmentioning

confidence: 99%

Microsatellite evolution: Mutations, sequence variation, and homoplasy in the hypervariable avian microsatellite locus HrU10

et al. 2008

View full text Add to dashboard Cite

BackgroundMicrosatellites are frequently used genetic markers in a wide range of applications, primarily due to their high length polymorphism levels that can easily be genotyped by fragment length analysis. However, the mode of microsatellite evolution is yet not fully understood, and the role of interrupting motifs for the stability of microsatellites remains to be explored in more detail. Here we present a sequence analysis of mutation events and a description of the structure of repeated regions in the hypervariable, pentanucleotide microsatellite locus HrU10 in barn swallows (Hirundo rustica) and tree swallows (Tachycineta bicolor).ResultsIn a large-scale parentage analysis in barn swallows and tree swallows, broods were screened for mutations at the HrU10 locus. In 41 cases in the barn swallows and 15 cases in the tree swallows, mutations corresponding to the loss or gain of one or two repeat units were detected. The parent and mutant offspring alleles were sequenced for 33 of these instances (26 in barn swallows and 7 in tree swallows). Replication slippage was considered the most likely mutational process. We tested the hypothesis that HrU10, a microsatellite with a wide allele size range, has an increased probability of introductions of interruptive motifs (IMs) with increasing length of the repeated region. Indeed, the number and length of the IMs was strongly positively correlated with the total length of the microsatellite. However, there was no significant correlation with the length of the longest stretch of perfectly repeated units, indicating a threshold level for the maximum length of perfectly repeated pentanucleotide motifs in stable HrU10 alleles. The combination of sequence and pedigree data revealed that 15 barn swallow mutations (58%) produced alleles that were size homoplasic to other alleles in the data set.ConclusionOur results give further insights into the mode of microsatellite evolution, and support the assumption of increased slippage rate with increased microsatellite length and a stabilizing effect of interrupting motifs for microsatellite regions consisting of perfect repeats. In addition, the observed extent of size homoplasy may impose a general caution against using hypervariable microsatellites in genetic diversity measures when alleles are identified by fragment length analysis only.

show abstract

“…Using this argument, Haldane (1935Haldane ( , 1947 was the first to estimate human mutation rates (3.2 × 10 -5 for haemophilia) with µ > ν, possibly by a factor of 10. Recent analyses show this to be of the correct order (e.g., Ellergren, 2002). Weinberg (1912b) was one of the first to recognize that mutation might maintain deleterious traits in this way, and also that mutation might be more frequent in males than in females, at a time when mutation was an underdeveloped and misunderstood concept.…”

Section: Subsequent Work On Hwementioning

confidence: 99%

A Century of Hardy–Weinberg Equilibrium

Mayo

2008

Twin Res Hum Genet

129

View full text Add to dashboard Cite

Hardy–Weinberg equilibrium (HWE) is the state of the genotypic frequency of two alleles of one autosomal gene locus after one discrete generation of random mating in an indefinitely large population: if the alleles areAandawith frequenciespandq(=1-p), then the equilibrium gene frequencies are simplypandqand the equilibrium genotypic frequencies forAA,Aaandaaarep2, 2pqandq2. It was independently identified in 1908 by G. H. Hardy and W. Weinberg after earlier attempts by W. E. Castle and K. Pearson. Weinberg, well known for pioneering studies of twins, made many important contributions to genetics, especially human genetics. Existence of this equilibrium provides a reference point against which the effects of selection, linkage, mutation, inbreeding and chance can be detected and estimated. Its discovery marked the initiation of population genetics.

show abstract

Human mutation—blame (mostly) men

Cited by 16 publications

References 15 publications

The ovotestis: an underdeveloped organ of evolution

The ovotestis: an underdeveloped organ of evolution

Microsatellite evolution: Mutations, sequence variation, and homoplasy in the hypervariable avian microsatellite locus HrU10

A Century of Hardy–Weinberg Equilibrium

Contact Info

Product

Resources

About