Sister grouping of chimpanzees and humans as revealed by genome-wide phylogenetic analysis of brain gene expression profiles

Abstract

Gene expression profiles from the anterior cingulate cortex (ACC) of human, chimpanzee, gorilla, and macaque samples provide clues about genetic regulatory changes in human and other catarrhine primate brains. The ACC, a cerebral neocortical region, has humanspecific histological features. Physiologically, an individual's ACC displays increased activity during that individual's performance of cognitive tasks. Of Ϸ45,000 probe sets on microarray chips representing transcripts of all or most human genes, Ϸ16,000 were commonly detected in human ACC samples and comparable numbers, 14,000 -15,000, in gorilla and chimpanzee ACC samples. Phylogenetic results obtained from gene expression profiles contradict the traditional expectation that the non-human African apes (i.e., chimpanzee and gorilla) should be more like each other than either should be like humans. Instead, the chimpanzee ACC profiles are more like the human than like the gorilla; these profiles demonstrate that chimpanzees are the sister group of humans. Moreover, for those unambiguous expression changes mapping to important biological processes and molecular functions that statistically are significantly represented in the data, the chimpanzee clade shows at least as much apparent regulatory evolution as does the human clade. Among important changes in the ancestry of both humans and chimpanzees, but to a greater extent in humans, are the up-regulated expression profiles of aerobic energy metabolism genes and neuronal functionrelated genes, suggesting that increased neuronal activity required increased supplies of energy. T raditionally, humans are presumed to have superior cognitive abilities and, thereby, to be very different from other animals. This presumed superiority lies in the supposed uniqueness of such human abilities as producing cultural artifacts and engaging in language and symbolic thought. Recent work, however, shows that chimpanzees, who are the sister group of humans (1-6), engage in culture (7), use tools (8-10), and display rudimentary forms of language (11-13). Moreover, with regard to DNA changes that alter proteins and are favored by natural selection, chimpanzees diverge about as much from the most recent common human-chimpanzee ancestor as do humans (1,14). Here, by estimating the relative abundance of transcribed messages of different expressed genes, we examine in humans and several other catarrhine primates gene expression profiles in an important cerebral region involved in cognition, the anterior cingulate cortex (ACC).The ACC is typically viewed as a bridge between paleocortex and neocortex but is actually part of the neocortex (15). Histologically, the ACC shows human-specific features. For example, clusters of spindle cell pyramidal neurons occur in the ACC of humans, lesser numbers in bonobo and common chimpanzees, lesser yet in gorillas, least in orangutans, and not at all in other primates and other mammals. Moreover, the spindle cells in humans are more than twice as large as in common and bonobo chimpanzees and three...

Differences in genetic and environmental influences on the human cerebral cortex associated with development during childhood and adolescence

“…An alternate, albeit related, explanation would be that regions with low genetic variance have greater functional constraints on their determinants of cortical thickness, such that genetic mutations influencing these regions will typically be eliminated quickly from the population through purifying selection. Comparative genomic experiments have shown that a subset of neurally-expressed genes have evolved more rapidly in humans than in other primates [Chimpanzee Sequencing and Analysis Consortium, 2005;Dorus et al, 2004;Khaitovich et al, 2005]; both gene expression changes and protein sequence modification have accelerated in humans relative to nonhuman primates [Caceres et al, 2003;Enard et al, 2002;Gu and Gu, 2003;Hsieh et al, 2003;Uddin et al, 2004]. The findings of increased genetic variance in evolutionarily recent structures may represent a remnant of these rapid neurogenetic changes that accompanied our divergence from other primates.…”

Evaluating the role of natural selection in the evolution of gene regulation

“…Some studies found a high rate of expression changes in the brain along the human lineage (Enard et al, 2002;Gu and Gu, 2003;Khaitovich et al, 2005a, b), while other studies found little or no evidence of an accelerated rate (Hsieh et al, 2003;Uddin et al, 2004;Gilad et al, 2006a, b). The reasons for these differences may be technical or methodological and have been discussed elsewhere (Gilad et al, 2006a, b).…”

Genomic signatures of diet-related shifts during human origins

“…For example, the differential expression of genes related to aerobic energy metabolism has only been found in studies examining expression in brain regions between species [67,69,91]. To get a more complete picture of the important functional shifts in gene expression between tissues and species, future studies will need to examine more tissues throughout the body.…”

“…(b) Evidence for changes in energy transport In brain tissues, there is a consistent pattern of changes in expression of genes critical to aerobic energy metabolism [67,69,71,91]. This includes categories such as oxidative phosphorylation, electron transport and other nuclearencoded genes that function in the mitochondria.…”