Posts Tagged ‘reproduction’

Regulating the age of puberty

Friday, February 19th, 2010

Initially posted 27 July 2009 by evomed

The age of puberty is a central feature of a species’ life history. The mechanism that controls the onset of sexual maturity evolved to allow for successful reproduction. Reproduction is energetically costly for the female and a degree of physical and psychosocial maturity is necessary for successful pregnancy and infant care. In humans, the timing of puberty evolved within ecological conditions that were radically different from ours and in which social independence was achieved at a younger age. Indeed, the gap between the sexual and social maturation continues to increase. Its steady growth is caused not just by the delay of social independence in the modern society but also by the falling age at puberty observed worldwide. It seems that the controls evolved to permit earlier puberty in the conditions of abundance are permanently switched on in our affluent society, where children are taller and heavier than ever before.

Studies published recently in Nature Genetics have begun to reveal some of the biological mechanisms behind the onset of puberty and of its link to the height and weight. A team led by John Perry conducted a meta-analysis of genome-wide association data of 17,520 women from eight different population-based cohorts. The women were all of European descent and had a self-reported age at menarche between 9 and 17 years, with the mean of 13.22 years. The SNPs that passed the significance threshold were all located at either chromosome 6 (6q21) or 9 (9q31.2). The strongest signal at 9q31.2 was observed with SNP rs2090409 (nearest genes TMEM38B, FKTN, FSD1L, TAL2 and ZNF462), where each A allele was associated with a 5-week reduction in menarcheal age. The T allele at rs7759938 within the 6q21 signal was also associated with a 5-week reduction in menarcheal age and it was found near a gene previously associated with a variation in human height, LIN28B. In the same issue of Nature Genetics, Ong at al confirmed the link between LIN28B on chromosome 6 and reduced age at menarche in several cohorts, with each copy of the major C allele at rs314276 reducing the age of menarche by 0.10-0.22 years. The same allele was then found to be associated with earlier breast development, and a higher BMI. In boys, it was found to be linked at age 15 with more advanced pubic hair stage, voice breaking status and tempo of height growth. In both sexes the allele was linked with faster tempo of growth in height between ages 7 and 11.

LIN28B shows high sequence, structural and functional homology with LIN28 on chromosome 1 and both exhibit sequence homology to lin-28 in the much-studied nematode worm Caenorhabditis elegans; deleterious mutations in that gene produce an abnormal tempo of development, while the enhancement of its expression by deletion of regulatory elements delays larval stage expression. It is thus suggested that LIN28B, the first cell marker associated with the timing of puberty, is associated with an evolutionarily old cell regulatory system of human growth and development.

While important, these studies explain only a small part of observed variation: even in homozygotes, the C allele at rs314276 upstream of LIN28B accounts for just a few months of the observed difference. These studies furthermore do not explain the ‘secular trend’ or the widely observed reduced age at puberty in the modern world. It is hoped that the location of other similar cell markers and a closer look into the regulation of their expression, especially during the plastic developmental period, will shed more light on this fundamental life phase.


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