Functional primate genomics—leveraging the medical potential

Abstract

Within biomedicine, comparative genomics is crucial for interpreting human genetic variants and building proper animal models. As our closest relatives, primates are of particular relevance in this frame work. Here, I review principles and concrete examples of this approach. Since one can expect that generating the necessary genomic DNA sequences will not be the major limiting factor in the near future, I argue that in analogy to human biomedicine, comprehensive phenotyping of different primates will be a crucial next step to tap the full potential of comparative genomics. Especially the possibility to generate pluripotent stem cells from primates should allow extending the comparative approach to many medically relevant questions.

The evolution of evolutionary molecular medicine

“…In a further important step, an "evolutionary" approach to medicine studies the relationship between genomic data from humans with the ones of hominids and primates, in relation to the differences in symptoms of diseases across these different species [3][4][5]. Direct medical applications of identifying sequence variations associated with specific diseases receive the most attention; however, new sequencing technologies are also transforming evolutionary biology in ways that will make it far more important for medicine.…”

“…Direct medical applications of identifying sequence variations associated with specific diseases receive the most attention; however, new sequencing technologies are also transforming evolutionary biology in ways that will make it far more important for medicine. We can now begin to answer questions about how life developed 3.5 billion years ago, when Homo sapiens diverged from African ancestors, when our species emerged from Africa, and even how much interbreeding occurred with Neanderthals [3]. Genomic data even allow inference about a previously unrecognized extinct line of hominids, the Denisova hominids.…”

On the apparent rarity of epithelial cancers in captive chimpanzees

“…Abundant data now indicate that we humans are very closely related to other hominids including chimpanzees, bonobos, gorillas and orangutans (the so-called 'great apes', hereafter called nonhuman hominids, or NHHs) [11][12][13]. Indeed, humans are closer genetically to chimpanzees and bonobos than they are to gorillas and orangutans.…”

“…Indeed, humans are closer genetically to chimpanzees and bonobos than they are to gorillas and orangutans. And humans are closer genetically to the chimpanzee/bonobo clade than mice and rats are to each other [12,13]. Thus, it was reasonable to expect that chimpanzees would be good models for understanding human disease [14].…”

Human Evolution: Enhancing the Brain

“…This is crucial to better understand human evolution. But it might also be an important approach to understand the molecular and cellular mechanisms of human biology [20]. 16 …”