Saturday, May 12, 2007

WHY AREN'T WE EXTINCT? ....................

Absolute Mutation Rate

"The total mutation frequency,as inferred from evolutionary studies,44), is something in the order of 100 new mutations per generation. This seems utterly frightening. Surely the overwhelming majority of these must be essentiallt neutral. More relevant is the frequency of new deleterious mutations, which is more than one per zygote.45)That is still high. WHY AREN'T WE EXTINCT?" emphasis mine

Department of Genetics, University of Wisconsin
: J Radiat Res (Tokyo). 2006;47 Suppl B:B75-82. Links
Age and sex effects on human mutation rates: an old problem with new complexities.Crow JF..

Base substitution mutations are far more common in human males than in females, and the frequency increases with paternal age. Both can be accounted for by the greater number of pre-meiotic cell divisions in males, especially old ones. In contrast, small deletions do not show any important age effect and occur with approximately equal frequency in the two sexes. Mutations in most genes include both types, and the sex and paternal age effect depends on the proportion of the two types. A few traits, of which Apert Syndrome is best understood, are mutation hot spots with all the mutations occurring in one or two codons, usually at one nucleotide. They occur with very high frequency almost exclusively in males and the frequency increases rapidly with paternal age. It has been suggested that the mutant cells have a selective advantage in the male germ-line prior to meiosis. Evidence for this surprising, but important, hypothesis is discussed. A possible mechanism is the conversion of asymmetrical stem-cell divisions into symmetric ones. Some traits with complex etiology show a slight paternal age effect. There is also a short discussion of the high deleterious mutation rate and the role of sexual reproduction in reducing the consequent mutation load.

PMID: 17019055 [PubMed - in process]


October 2003, Volume 11, Number 10, Pages 754-759
Table of contents Previous Article Next PDF


Mercè Bosch1, Osvaldo Rajmil2, Josep Egozcue3 and Cristina Templado1

1Departament de Biologia Cel.lular, Fisiologia i Immunologia,
Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain

2Servei d'Andrologia, Fundació Puigvert, Barcelona 08025, Spain

3Departament de Biologia Cel.lular, Fisiologia i Immunologia, Facultat de Ciències, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain

Correspondence to: C Templado, Departament de Biologia, Fisiologia i Immunologia, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain. Tel: +34 93 -581 3569; Fax: +34 93 581 1025; E-mail:


A simultaneous four-colour fluorescence in situ hybridisation (FISH) assay was used in human sperm in order to search for a paternal age effect on: (1) the incidence of structural aberrations and aneuploidy of chromosome 9, and (2) the sex ratio in both normal spermatozoa and spermatozoa with a numerical or structural abnormality of chromosome 9. The sperm samples were collected from 18 healthy donors, aged 24-74 years (mean 48.8 years old). Specific probes for the subtelomeric 9q region (9qter), centromeric regions of chromosomes 6 and 9, and the satellite III region of the Y chromosome were used for FISH analysis. A total of 190 117 sperms were evaluated with a minimum of 10 000 sperm scored from each donor. A significant linear increase in the overall level of duplications and deletions for the centromeric and subtelomeric regions of chromosome 9 (P0.002), chromosome 9 disomy (P<0.0001) as well as diploidy (P<0.0001) was detected in relation to age. The percentage of increase for each 10-year period was 29% for chromosome 9 disomy, 18.8% for diploidy, and ranged from 14.6 to 28% for structural aberrations. Our results indicate a linear increase in structural aberrations and disomy for chromosome 9 in sperm with respect to age.

European Journal of Human Genetics

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