"A Very Muscular Baby Offers Hope Against Diseases"

Occurrence MSTN polymorphisms across human populations.

To follow up my "Super Muscular Puppies" blog post, this articles concern natural variation of the myostatin gene (MSTN) in human populations. Mice with knocked out MSTN show massive increases in muscle cell number and size. Seven years after the publication of this finding, a case study of a child with a homozygous loss of function mutation in MSTN was documented (also covered in an article with the fantastic title, "A Very Muscular Baby Offers Hope Against Diseases"). This child, a German boy named Liam Hoekstra, showed a similar phenotype to the KO mice in that he had visibly increased muscle mass relative to a typical newborn. By the age of 3 years, it was claimed that Liam had unusual strength for a child his age (though this was never formally tested). Studying cases like that of Liam holds promise for developing muscular wasting disease therapies.

In 2006, another study tested for evidence of positive selection of the MSTN gene across human populations and between species. A positive selection analysis calculated dN/dS ratios (the proportion of non-synonymous mutations to synonymous mutations) across 23 vertebrates (mostly mammals) and found a high degree of conservation of this gene. However within human populations, several allelic variants produced by SNPs were present in a high proportion (up to 31%) in sub-Saharan populations. Rather than resulting in a complete loss of function, these mutations were associated with a partial reduction in the ability of MSTN to inhibit muscle growth. However the exact functional consequences of these mutations in these individuals is still unclear, as a previous study failed to find associations between MSTN polymorphisms and muscular strength. The authors of the 2006 article claim that the mutations seen in sub-Saharan populations may result in increases muscle mass (not tested in these individuals) which could protect against famine (a counterintuitive explanation given the high metabolic cost of muscle tissue).