Comparing the human and chimpanzee genomes: Searching for needles in a haystack

Abstract

The chimpanzee genome sequence is a long-awaited milestone, providing opportunities to explore primate evolution and genetic contributions to human physiology and disease. Humans and chimpanzees shared a common ancestor ∼5-7 million years ago (Mya). The difference between the two genomes is actually not ∼1%, but ∼4%-comprising ∼35 million single nucleotide differences and ∼90 Mb of insertions and deletions. The challenge is to identify the many evolutionarily, physiologically, and biomedically important differences scattered throughout these genomes while integrating these data with emerging knowledge about the corresponding "phenomes" and the relevant environmental influences. It is logical to tackle the genetic aspects via both genome-wide analyses and candidate gene studies. Genome-wide surveys could eliminate the majority of genomic sequence differences from consideration, while simultaneously identifying potential targets of opportunity. Meanwhile, candidate gene approaches can be based on such genomic surveys, on genes that may contribute to known differences in phenotypes or disease incidence/severity, or on mutations in the human population that impact unique aspects of the human condition. These two approaches will intersect at many levels and should be considered complementary. We also cite some known genetic differences between humans and great apes, realizing that these likely represent only the tip of the iceberg.Humans (Homo sapiens) and chimpanzees (Pan troglodytes) last shared a common ancestor ∼5-7 million years ago (Mya) (Chen and Li 2001;Brunet et al. 2002). What makes humans different from their closest evolutionary relatives, and how, why, and when did these changes occur? These are fascinating questions, and a major challenge is to explain how genomic differences contributed to this process

How pleiotropic genetics of the musculoskeletal system can inform genomics and phenomics of aging

“…One step to extend the utility of the abundant genome data is to have the phenome much better defined (Varki and Altheide 2005). We propose to outline human biological aging using the musculoskeletal aging phenotypes as an example and a starting point, with further addition of other relevant biomarkers.…”

“…The phenomic approach orients genetic investigation around common biologic pathways leading to disease (Varki and Altheide 2005). There are two main premises of the phenomic approach: first, since relations between phenotypes often reflect a biologic and functional interaction at the gene level, several investigators (Bilder et al 2009) have argued for using phenotypic relations to discern the underlying biology (as exemplified by pleiotropic findings for several pathologies; Helgadottir et al 2007;Saxena et al 2007;Scott et al 2007;McPherson et al 2007).…”

More genes underwent positive selection in chimpanzee evolution than in human evolution

“…are highly similar at the genomic level (1-6), they differ in many morphological, physiological, and behavioral traits (7). Phenotypically, modern humans appear to have changed considerably more than modern chimps from their common ancestors (7)(8)(9)(10).…”

“…Phenotypically, modern humans appear to have changed considerably more than modern chimps from their common ancestors (7)(8)(9)(10). Many of these evolutionary modifications in humans, such as the origins of bipedalism, speech and language, and other high-order cognitive functions, are widely thought to be adaptive (11)(12)(13).…”

The evolution of the Th2 immune responses and its relationships with parasitic diseases and allergy

“…Es difícil establecer con certeza las causas de la aparición de nuevos genes y genotipos; pero, además, en el humano se desconocen todavía las bases genotípicas de la mayoría de los rasgos (52). En términos generales, aceptamos que las variaciones genéticas se dan por azar y como consecuencia de factores tanto del ambiente externo como del intracelular, pero las causas de fenómenos específicos, como la duplicación génica, generadora de diversidad y cada vez mejor explicada en términos operativos, continúan sin conocerse (53).…”