The role of GHR and IGF1 genes in the genetic determination of African pygmies’ short stature

Abstract

African pygmies are at the lower extreme of human variation in adult stature and many evolutionary hypotheses have been proposed to explain this phenotype. We showed in a recent study that the difference in average stature of about 10 cm observed between contemporary pygmies and neighboring non-pygmies has a genetic component. Nevertheless, the genetic basis of African pygmies' short stature remains unknown. Using a candidate-gene approach, we show that intronic polymorphisms in GH receptor (GHR) and insulin-like growth factor 1 (IGF1) genes present outlying values of the genetic distance between Baka pygmies and their non-pygmy Nzimé neighbors. We further show that GHR and IGF1 genes have experienced divergent natural selection pressures between pygmies and non-pygmies throughout evolution. In addition, these SNPs are associated with stature in a sample composed of 60 pygmies and 30 non-pygmies and this association remains significant when correcting for population structure for the GHR locus. We conclude that the GHR and IGF1 genes may have a role in African pygmies' short stature. The use of phenotypically contrasted populations is a promising strategy to identify new variants associated with complex traits in humans.

Reproduction in the Baka pygmies and drop in their fertility with the arrival of alcohol

“…This agrees with the pattern of growth described for the Baka, who reach maturity (menarche, first reproduction) at a similar age as nonforager populations (11). The short stature of the Baka is not a consequence of early cessation of growth, as has been suggested for the Aeta, but results from a slower rate of growth during infancy (11), which has a genetic foundation (39)(40)(41). Therefore, high mortality rates (infant, juvenile, or adult) may influence the timing of development (38,42) but do not seem to be linked with adult body size.…”

VDR gene methylation as a molecular adaption to light exposure: Historic, recent and genetic influences

“…Pygmies cease growth early at around 12 years and exhibit no adolescent growth spurt. Other theories exist, and suggest the GHBP/GHR/IGF1 system may be altered (Becker et al, ), and that heritable epigenetics is involved by linking environment to modification in gene expression, with geographically distant pygmy groups likely evolving their short stature independently (Migliano et al, ).…”

Growth pattern from birth to adulthood in African pygmies of known age

“…Studies of genetic introgression have shown that the pygmy phenotype stems from genetic foundations 15 , perhaps involving a deficiency in the GH–IGF axis 16 . Although some particular SNPs in genes associated with stature have been identified in pygmies 17 18 , the exact genetic foundation remains elusive 19 .…”