The findings relate to the genetics of modern Pima Indians who have an unusually high rate of obesity but could be extrapolated to all people. Their obesity is thought to be linked to a thrifty metabolism that allowed them to metabolize food more efficiently in times when little was available but causes problems when food is in abundance.

Mark Rowe, David McClellan, and colleagues at Brigham Young University in Provo, Utah, USA, have studied the effect of evolutionary selection on Pima Indians, a people indigenous to the present-day Sonora desert of Arizona and New Mexico. The researchers anticipated an effect consistent with higher metabolic efficiency among these people and focused specifically on recently discovered variations in their mitochondrial DNA, so-called SNPs, or single nucleotide polymorphisms.

The metabolic rates of 200 obese Pima individuals were measured and revealed that two of the three known SNPs influence metabolic efficiency. The researchers then used the genetics software TreeSAAP, to analyze the biochemical changes caused by these SNPs and then tracked the evolutionary selection of these genetic variations in 107 different types of mammals. This allowed them to propose a mechanism by which these SNPs affect the mitochondrial respiratory chain and consequently increase metabolic efficiency in the Pima people.

The team suggests that an increased metabolic efficiency could have been an evolutionary advantage. The SNPs may have persisted because they helped the Pima survive the harsh dietary environment of the Sonora desert throughout the history of the people. In the current environment of caloric over-consumption an increased efficiency is unfavorable and may contribute to the high rates of obesity among the Pimas.

While the Pima Indians are an extreme case, the entire human population may also have evolved in a restricted caloric environment, say the researchers. Many populations may exhibit similar SNPs that were advantageous to our ancestors but may now be detrimental. The presence of these SNPs may thus provide one explanation as to why obesity is so rife in the 21st century.

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The MGH team analyzed the PROK2 genes of 100 study participants: 50 with Kallmann syndrome and 50 with IHH and a normal sense of smell. Three members from the same family in Portugal “ two brothers and a sister “ had identical defects in both copies of the PROK2 gene. Further study of this family revealed another brother with the mutation in only one PROK2 copy and a normal reproductive history. Five siblings of these individuals “ now in their 70s “ had died in infancy; similar early deaths have been seen in the PROK2-deficient mice. Interestingly, while the two affected brothers both had Kallmann syndrome, their affected sister had a normal sense of smell but did not experience normal puberty.

Until recently, IHH with a normal sense of smell and Kallmann syndrome with no sense of smell had been considered two distinct clinical entities, says Pitteloud, an assistant professor of Medicine at Harvard Medical School. We now have described several kindreds in which different family members exhibit both syndromes yet harbor the identical mutation. So, it looks like additional gene defects or environmental cues modify how these syndromes develop in affected families.

The collaborative UC Irvine team was led by Qun-Yong Zhou, PhD, a professor of Pharmacology in its School of Medicine. His group has made fundamental contributions to the understanding of the neurobiological functions of prokineticin and its receptors. Their analysis of the reproductive status of mice lacking functional copies of Prok2 gene revealed that the animals' reproductive defect is due to the abnormal migration of neurons that secrete GnRH.

Many recessive human genetic disorders, particularly the ones that have associated infertility symptom, are very difficult or almost infeasible to investigate using genetic analysis. The current study provides an elegant example how mouse studies can pinpoint the underlying genetic cause for human IHH disorders. says Zhou.

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