Research using a new method of identifying genes most altered in humans has pinpointed genes involved in birth timing, potentially also implicated in preterm birth. Investigators from Vanderbilt University, Washington University and the University of Helsinki report that variations in the gene for the follicle stimulating hormone receptor (FSHR) may increase a woman's risk for delivering her infant prematurely. The study will appear in the open-access journal PLoS Genetics on April 14.

More than half a million babies per year in the United States - one in eight - are born prematurely (before 37 weeks of gestation). Premature babies face an increased risk of death and serious short- and long-term medical complications, yet there are no adequate therapies to prevent preterm birth.

The investigators proposed that genes involved in human birth timing have evolved faster than in other species, decreasing the length of gestation to accommodate uniquely human constraints, a large head and a narrow pelvis. In the current report, they provide evidence that gestation length has decreased in the evolutionary lineage leading to modern humans, and that human gestation is shorter than predicted compared to other primates.

To find genes that have changed to regulate birth timing, the researchers used comparative genomics to identify a set of "human accelerated genes" - genes that were most altered in humans compared to six other animals. They screened 150 of these accelerated genes in Finnish mothers and found that certain variations in the (FSHR) gene were more frequent in mothers who had experienced preterm birth.

The same variations may also be associated with preterm birth in African Americans. The (FSHR) gene has not previously been implicated in the timing for birth or preterm birth risk.

"Studies in larger cohorts could point to additional accelerated genes with roles in birth timing and provide new targets for therapeutic or preventive measures", said co-authors Louis Muglia and Justin Fay.

Financial Disclosure: This work was supported by grants from the Children's Discovery Institute at Washington University School of Medicine and St. Louis Children's Hospital awarded to Justin Fay and Louis Muglia and from the March of Dimes awarded to Louis Muglia and Errol Norwitz. This research was also supported by T32 GM081739 from the National Institute of General Medical Science and the Mr. and Mrs. Spencer T. Olin Fellowship for Women in Graduate Study at Washington University in St. Louis awarded to Jevon Plunkett, a grant from the Sigrid Juselius Foundation awarded to Mikko Hallman, a grant from the Signe and Anne Gyllenberg foundation to Vineta Fellman, and grants from the Academy of Finland to Ritva Haataja and Mikko Hallman. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Citation: Plunkett J, Doniger S, Orabona G, Morgan T, Haataja R, et al. (2011) An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing. PLoS Genet 7(4): e1001365. doi:10.1371/journal.pgen.1001365

PLoS Genetics