June 6, 2008 A team of researchers at Harvard University have modeled in the laboratory a primitive cell, or protocell, that is capable of building, copying and containing DNA.
Since there are no physical records of what the first primitive cells on Earth looked like, or how they grew and divided, the research team's protocell project offers a useful way to learn about how Earth's earliest cells may have interacted with their environment approximately 3.5 billion years ago.
The protocell's fatty acid membrane allows chemical compounds, including the building blocks of DNA, to enter into the cell without the assistance of the protein channels and pumps required by today's highly developed cell membranes. Also unlike modern cells, the protocell does not use enzymes for copying its DNA.
Led by Jack W. Szostak of the Harvard Medical School, the research team published its findings in the June 4, 2008, edition of the journal Nature's advance online publication.
"Szostak's group took a creative approach to this research challenge and made a significant contribution to our understanding of small molecule transport through membranes," said Luis Echegoyen, director of the NSF Division of Chemistry.
Some scientists have proposed that ancient hydrothermal vents may have been sites where prebiotic molecules--molecules made before the origin of life, such as fatty acids and amino acids--were formed.
When fatty acids are in an aqueous environment, they spontaneously arrange so that their hydrophilic, or water-loving, "heads" interact with the surrounding water molecules and their hydrophobic, or water-fearing, "tails" are shielded from the water, resulting in the formation of tiny spheres of fatty acids called micelles.
Depending upon chemical concentrations and the pH of their environment, micelles can convert into layered membrane sheets or enclosed vesicles. Researchers commonly use vesicles to model the cellular membranes of protocells.
When the team started its work, the researchers were not sure that the building blocks required for copying the protocell's genetic material would be able to enter the cell.
"By showing that this can happen, and indeed happen quite efficiently, we have come a little closer to our goal of making a functional protocell that, in the right environment, is able to grow and divide on its own," said Szostak.
"We have found that membranes made from fatty acids and related molecules -- the most likely components of primitive cell membranes -- have properties very different from those of the modern cell membrane, which uses specialized pumps, channels or pores to control what gets in and out," says Jack Szostak, PhD, of the MGH Department of Molecular Biology and Center for Computational and Integrative Biology, the report's senior author. "Our report shows that very primitive cells may have absorbed nutrients from their environment, rather than having to manufacture needed materials internally, which supports one of two competing theories about fundamental properties of these cells."
Szostak's team carefully analyzed vesicles comprised of different fatty acid molecules and identified particular features that made membranes more or less permeable to potential nutrient molecules. They found that, while large molecules such as strands of DNA or RNA could not pass through fatty acid membranes, the simple sugar molecules and individual nucleotides that make up larger nucleic acids easily crossed the membrane.
To further explore the function of a fatty acid cell membrane, the researchers used activated nucleotides they developed for this study that will copy a DNA template strand without needing the polymerase enzyme usually required for DNA replication. After placing template molecules inside fatty-acid vesicles and adding the activated nucleotides to the external environment, they found that additional DNA was formed within the vesicles, confirming that the nucleotide molecules were passing through the fatty-acid membranes.
Co-authors of the Nature paper include Sheref S. Mansy, Jason P. Schrum, Mathangi Krishnamurthy, Sylvia Tobe and Douglas A. Treco of the Szostak Laboratory.
The research was supported with funding from the National Science Foundation (Division of Chemistry award number 0434507). Jack W. Szostak was also supported by National Aeronautics and Space Administration Exobiology Program award number EXB02-0031-0018. Sheref S. Mansy was supported by National Institutes of Health award number F32 GM07450601.
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