Human pregnancy is weird -- new research adds to the mystery

April 21, 2020

BUFFALO, N.Y. -- From an evolutionary perspective, human pregnancy is quite strange, says University at Buffalo biologist Vincent Lynch.

"For example, we don't know why human women go into labor," Lynch says. "Human pregnancy tends to last longer than pregnancy in other mammals if you adjust for factors like body size. The actual process of labor tends to last longer than in other animals. And human pregnancy and labor are also much more dangerous."

With these oddities in mind, Lynch and colleague Mirna Marinic set out to investigate the evolution of a gene that helps women stay pregnant: the progesterone receptor gene.

But the results of the study only add to the mystery, says Lynch, PhD, an assistant professor of biological sciences in the UB College of Arts and Sciences.

Unexpected findings about a gene that's critical to pregnancy

Past research has shown that the progesterone receptor gene underwent rapid evolution in humans, and some scientists have suggested that these swift changes occurred because they improved the function of the gene. This is called positive selection.

But Lynch and Marinic's study -- published online on April 17 in the journal PLOS Genetics -- draws a different conclusion.

Their research finds that while the progesterone receptor gene evolved rapidly in humans, there's no evidence to support the idea that this happened because those changes were advantageous. In fact, the evolutionary force of selection was so weak that the gene accumulated many harmful mutations as it evolved in humans, Lynch says.

The results come from an analysis of the DNA of 115 mammalian species. These included a variety of primates, ranging from modern humans and extinct Neanderthals to monkeys, lemurs and lorises, along with non-primate mammalian species such as elephants, pandas, leopards, hippos, aardvarks, manatees and walruses.

The findings were a surprise, Lynch says.

"We expected something very different. It opens up this mystery that we didn't anticipate," he says. "I thought that the progesterone receptor gene would have evolved to respond better to progesterone, to be better at suppressing inflammation or contractions to keep us pregnant for longer. It looks like it's the reverse: In human pregnancy, there's just an incredible amount of progesterone around, and yet the gene is less good at doing its job. I wonder if this might predispose us to things like preterm birth, which is not that common in other animals."

"Pregnancy is such an everyday event -- none of us would be here without it -- and yet, so many aspects of this process remain puzzling," says Marinic, PhD, a postdoctoral researcher in the University of Chicago Department of Organismal Biology and Anatomy. "This study focused on an essential ingredient, progesterone signaling via progesterone receptors, and our results add another step toward deeper understanding of specificities of human pregnancy."

The progesterone receptor gene is crucial to pregnancy because it provides cells with instructions for how to create tiny structures called progesterone receptors.

During human pregnancy, these receptors detect the presence of progesterone, an anti-inflammatory hormone that pregnant women and the placenta produce at various points in time. When progesterone is present, the receptors jump into action, triggering processes that help keep women pregnant in part by preventing the uterus from contracting, reducing uterine inflammation, and suppressing the maternal immune response to the fetus, Lynch says.

Evolution changed the function of progesterone receptors in humans

In addition to exploring the evolutionary history of the progesterone receptor gene, Lynch and Marinic conducted experiments to test whether mutations in the human version of the gene altered its function. The answer is yes.

As the scientists wrote in their paper, "We resurrected ancestral forms of the progesterone receptor and tested their ability to regulate a target gene. We found that the human progesterone receptor forms have changed in function, suggesting the actions regulated by progesterone may also be different in humans. Our results suggest caution in attempting to apply findings from animal models to progesterone biology of humans."
-end-
The research was funded by the March of Dimes and the Burroughs Wellcome Fund Preterm Birth Initiative.

University at Buffalo

Related DNA Articles from Brightsurf:

A new twist on DNA origami
A team* of scientists from ASU and Shanghai Jiao Tong University (SJTU) led by Hao Yan, ASU's Milton Glick Professor in the School of Molecular Sciences, and director of the ASU Biodesign Institute's Center for Molecular Design and Biomimetics, has just announced the creation of a new type of meta-DNA structures that will open up the fields of optoelectronics (including information storage and encryption) as well as synthetic biology.

Solving a DNA mystery
''A watched pot never boils,'' as the saying goes, but that was not the case for UC Santa Barbara researchers watching a ''pot'' of liquids formed from DNA.

Junk DNA might be really, really useful for biocomputing
When you don't understand how things work, it's not unusual to think of them as just plain old junk.

Designing DNA from scratch: Engineering the functions of micrometer-sized DNA droplets
Scientists at Tokyo Institute of Technology (Tokyo Tech) have constructed ''DNA droplets'' comprising designed DNA nanostructures.

Does DNA in the water tell us how many fish are there?
Researchers have developed a new non-invasive method to count individual fish by measuring the concentration of environmental DNA in the water, which could be applied for quantitative monitoring of aquatic ecosystems.

Zigzag DNA
How the cell organizes DNA into tightly packed chromosomes. Nature publication by Delft University of Technology and EMBL Heidelberg.

Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.

DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.

A new spin on DNA
For decades, researchers have chased ways to study biological machines.

From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.

Read More: DNA News and DNA Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.