Animal Rights

More Differences Among Primates

| by Dr Ray Greek

As more is learned about the genetic makeup of primates, the more we understand why nonhuman primates cannot predict human response to drugs and disease. From ScienceDaily  ( /releases/2011/03/110317172047.htm) (sorry, the site does not want to allow me to insert the ScienceDaily links for some reason):

A robust new phylogenetic tree resolves many long-standing issues in primate taxonomy. The genomes of living primates harbor remarkable differences in diversity and provide an intriguing context for interpreting human evolution. The phylogenetic analysis was conducted by international researchers to determine the origin, evolution, patterns of speciation, and unique features in genome divergence among primate lineages . . .

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The article can be found in PLoS Genetics. The authors conclude:

Primate genomes harbor remarkable differences in patterns of speciation, genome diversity, rates of evolution and frequency of insertion/deletion events that are fascinating in their own right, but also provide needed insight into human evolution. Advances in human biomedicine including those focused on changes in genes triggered or disrupted in development, resistance/susceptibility to infectious disease, cancers, mechanisms of recombination and genome plasticity, cannot be adequately interpreted in the absence of a precise evolutionary context or hierarchy. Resolution of the primate species phylogeny here provides a validated framework essential in the development, interpretation and discovery of the genetic underpinnings of human adaptation and disease.

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From another article discussed at ScienceDaily ( /releases/2011/02/110228104318.htm):

Part of the answer to how and why primates differ from other mammals, and humans differ from other primates, may lie in the repetitive stretches of the genome that were once considered "junk."

A new study by researchers at the University of Iowa Carver College of Medicine finds that when a particular type of repetitive DNA segment, known as an Alu element, is inserted into existing genes, they can alter the rate at which proteins are produced -- a mechanism that could contribute to the evolution of different biological characteristics in different species.

"Repetitive elements of the genome can provide a playground for the creation of new evolutionary characteristics," Xing said. "By understanding how these elements function, we can learn more about genetic mechanisms that might contribute to uniquely human traits."

Alu elements are a specific class of repetitive DNA that first appeared about 60 to 70 million years ago during primate evolution. They do not exist in genomes of other mammals. Alu elements are the most common form of mobile DNA in the human genome, and are able to transpose, or jump, to different positions in the genome sequence. When they jump into regions of the genome containing existing genes, these elements can become new exons -- pieces of messenger RNAs that carry the genetic information.

The article can be found at the Proceedings of the National Academy of Sciences (PNAS).

From Howard Hughes Medical Institute:

A new study demonstrates that specific traits that distinguish humans from their closest living relatives – chimpanzees, with whom we share 96

percent of our DNA – can be attributed to the loss of chunks of DNA that control when and where certain genes are turned on. The finding mirrors accumulating evidence from other species that changes to regulatory regions of DNA – rather than to the genes themselves – underlie many of the new features that organisms acquire through evolution.

Seeking specific genetic changes that might be responsible for the evolution of uniquely human traits, Howard Hughes Medical Institute investigator David Kingsley and colleagues at Stanford University scanned the human genome for features that set us apart from other mammals. The team found 510 segments that are present in chimps and other animals but missing from the human genome. Only one of the missing segments would actually disrupt a gene; the remaining 509 affect the DNA that surrounds genes, where regulatory sequences lie.

Careful analysis of a handful of these segments demonstrated that loss of regulatory DNA could explain how humans developed some features not found in other animals -- such as big brains – as well as how they lost features common in other species, such as sensory whiskers and spiny penises.

The article is published in Nature.

The press release continues:

Genes—segments of DNA that carry the blueprints for proteins—make up less than two percent of the human genome. Hidden within the remainder of our more than three billion base pairs of DNA are regulatory sequences that control when and where genes are expressed. Direct alterations to a gene can have dramatic effects, sometimes killing an organism or rendering it sterile. "In contrast, if you alter the way [a gene] turns on or off at a particular place in development, that can have a very large effect on a particular structure, but still preserve the other functions of the gene," Kingsley says. "That tends to be the sort of alternation that's favored when a new trait is evolving."

Kingsley's previous work with stickleback fish, a small spiny fish whose recent and rapid adaptation to a wide range of aquatic environments has made it ideal for evolutionary studies, have shown time and again that changes in regulatory DNA can have profound effects on an organism's traits. So when Kingsley and his colleagues searched for regions of the genome common to chimps, macaques, and mice but missing in the human genome, they weren't surprised that the sequence differences they found were almost exclusively outside of genes.

As I have said many times, small difference on the genetic level, like those described above, can result in dramatic differences in drug and disease response. This is exactly what we see when we use animals to predict human response; the animals, even nonhuman primates, do not respond the same way as humans often enough to be said to be predictive (unless of course you count fortunetellers and psychics as predictive). The more science learns about the genetic differences between humans and other primates the more this notion is reinforced.

I should also note that the above studies are examples of comparative research and I have acknowledged many times that such research is informative about what makes animal species different from one another. Such research is scientifically viable and makes no claims to be predictive for human response to drugs and disease. Granted, the knowledge gained may inform us as to why different animals react differently to drugs and disease but the studies themselves do not claim to be predictive for human response. This is an example of using animals and or their tissues in basic research and, as I have said before, such research is scientifically viable.

None of the above information will make any difference to the vivisection activist that claims predictability for animal models, as his concern is not with science but rather with money and prestige. Nonetheless, such data does eventually filter down into society and this eventually forces informed people to ask animal modelers to justify their actions.