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Difference Between Humans And Apes Linked To A Missing Oxygen Atom

Date:
September 29, 1998
Source:
University Of California, San Diego
Summary:
The differences between humans and apes are physically and functionally apparent, but genetically humans are extraordinarily similar to apes, especially to the chimpanzee and the bonobo (pygmy chimpanzee).

The differences between humans and apes are physically and functionally apparent, but genetically humans are extraordinarily similar to apes, especially to the chimpanzee and the bonobo (pygmy chimpanzee).

"We are so close in our DNA that if you were a visitor from another planet analyzing DNA samples of earth species, you would assume that there were greater differences between chimpanzees and gorillas than between chimpanzees and humans," said Ajit Varki, M.D., Professor of Medicine with the UCSD Cancer Center and Divisions of Hematology-Oncology and Cellular and Molecular Medicine at the University of California, San Diego. Varki is senior author of two new papers describing a genetic mutation at the root of a structural difference between an important cell surface molecule common in humans and chimpanzees.

In a paper published in the September 28 issue of the Proceedings of the National Academy of Sciences, Varki and a team of researchers from UCSD, the San Diego Veterans Affairs Medical Center, the Living Links Center of the Yerkes Primate Center, the Howard Hughes Medical Institute at Emory University, and Baylor College of Medicine describe a missing enzymatic action resulting from a mutated gene in humans that is the basis for the lack of a single oxygen atom in an otherwise identical sialic acid molecule.

"It has been known for a while that the DNA code of humans and chimpanzees is very similar," said Varki. "Thus, the obvious differences in physical appearance and functional abilities are likely to be explained by relatively few differences in the underlying genetic code. We have found what appears to be the first known major biochemical and genetic difference between humans and chimpanzees. For various reasons, the finding is an intriguing one, but further work is needed to determine its precise significance."

Sialic acids are a type of sugar molecule found on cell surfaces. These molecules play an important role in cell-to-cell communication, serving as binding sites for receptors on other cells in the body, and for a number of pathogens, including those that cause cholera, influenza and malaria.

The two predominant forms of sialic acid in animals are N-acetyl-neuraminic acid, or Neu5Ac, and N-glycolyl-neuraminic acid, or Neu5Gc. Because of the missing enzyme, humans only express Neu5Ac, which is different from Neu5Gc only by a single oxygen atom. Traces of Neu5Gc can be found in human fetal tissue and in certain human tumors, and humans with certain malignancies or certain inflammatory or infectious diseases develop antibodies against Neu5Gc.

Apes, on the other hand, are not known to develop certain cancers and also appear immune to some of the infectious diseases that plague humans. Varki and colleagues also note the intriguing fact that while Neu5Gc is found throughout the mammalian body, it appears to be suppressed in the mammalian brain, including the ape brain. Further studies are being conducted to explore the significance, if any, of the complete lack of this sialic acid in the brain.

In PNAS, the team reports cloning the human and chimpanzee hydroxylase cDNAs, and identifying a mutation in the coding region of the human cDNA that regulates hydroxylase activity. The same gene in apes codes for a hydroxylase enzyme which adds this atom to the sialic acid molecule, but due to a mutation at some point in human evolution, the human gene lacks this coding section, accounting for the structural difference in the molecule.

Similar findings in humans were recently reported by a group of Japanese scientists based at the Tokyo Metropolitan Institute, but Varki's team includes a complete cDNA sequence of both humans and chimpanzees which clearly establishes that the genetic mutation occurred after the lineage leading to modern humans diverged from the common ancestor with the chimpanzee and bonobo.

These findings and their implications are also discussed in the October 1 publication of the American Journal of Physical Anthropology, co-authored by Varki, Elaine Muchmore and Sandra Diaz, all of the UCSD Cancer Center and Cellular and Molecular Medicine program of the University of California, San Diego and the San Diego Veterans Affairs Medical Center.

"It...remains to be seen if this loss of expression of a common gene product can explain any of the major changes that occurred during hominid evolution, and thus any of the morphological and functional differences between humans and great apes," they write in the AJPA paper. "...Apart from altering interactions with extrinsic microbial agents, can the loss of Neu5Gc explain intrinsic differences between humans and the great apes? ...(T)he biological situation resulting from the loss of sialic acid hydroxylation may be very complex, and could affect the growth, development and function of multiple systems."

In both papers, the authors urge further comparative work on the biochemical differences between the great apes and humans, in order to better understand the molecular basis for human evolution.

Co-authors of the PNAS paper are Hsun-Hua Chou, Hiromu Takematsu and Sandra Diaz of the Varki laboratory at UCSD; Stephen T. Warren and Jane Iber of the Living Links Center of the Yerkes Primate Center, Howard Hughes Medical Institute and Departments of Biochemistry, Pediatrics and Genetics at Emory University School of Medicine; Elizabeth Nickerson and Kerry L. Wright of the Department of Molecular and Human Genetics at Baylor College of Medicine; and Elaine Muchmore of the San Diego Veterans Affairs Medical Center.

Varki, who is also affiliated with the Living Links Center of the Yerkes Primate Center, is currently President of the American Society for Clinical Investigation (ASCI), one of North America's oldest and most respected medical honor societies.


Story Source:

The above story is based on materials provided by University Of California, San Diego. Note: Materials may be edited for content and length.


Cite This Page:

University Of California, San Diego. "Difference Between Humans And Apes Linked To A Missing Oxygen Atom." ScienceDaily. ScienceDaily, 29 September 1998. <www.sciencedaily.com/releases/1998/09/980929073615.htm>.
University Of California, San Diego. (1998, September 29). Difference Between Humans And Apes Linked To A Missing Oxygen Atom. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/1998/09/980929073615.htm
University Of California, San Diego. "Difference Between Humans And Apes Linked To A Missing Oxygen Atom." ScienceDaily. www.sciencedaily.com/releases/1998/09/980929073615.htm (accessed July 28, 2014).

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