Human brain evolution: From gene discovery to phenotype discovery

Abstract

The rise of comparative genomics and related technologies has added important new dimensions to the study of human evolution. Our knowledge of the genes that underwent expression changes or were targets of positive selection in human evolution is rapidly increasing, as is our knowledge of gene duplications, translocations, and deletions. It is now clear that the genetic differences between humans and chimpanzees are far more extensive than previously thought; their genomes are not 98% or 99% identical. Despite the rapid growth in our understanding of the evolution of the human genome, our understanding of the relationship between genetic changes and phenotypic changes is tenuous. This is true even for the most intensively studied gene, FOXP2, which underwent positive selection in the human terminal lineage and is thought to have played an important role in the evolution of human speech and language. In part, the difficulty of connecting genes to phenotypes reflects our generally poor knowledge of human phenotypic specializations, as well as the difficulty of interpreting the consequences of genetic changes in species that are not amenable to invasive research. On the positive side, investigations of FOXP2, along with genomewide surveys of gene-expression changes and selection-driven sequence changes, offer the opportunity for "phenotype discovery," providing clues to human phenotypic specializations that were previously unsuspected. What is more, at least some of the specializations that have been proposed are amenable to testing with noninvasive experimental techniques appropriate for the study of humans and apes.primate | hominid | phylogeny T he ability to sequence the whole genome of a species, along with other advances in molecular biology and in bioinformatics, have ushered in a remarkable new era of human evolutionary studies. We might reasonably expect that these developments have advanced our understanding of the evolution of the human brain and its functional capacities. Here, I will argue that this is the case, although the path connecting genes to phenotypes is not as straight as one might suppose. Comparative Genetic and Molecular BackgroundTo appreciate how far we have come in this field, and what we have yet to accomplish, it is useful to note where we were in the late 1990s, just before the comparative genomics revolution. What were scientists' expectations about the kinds of molecular changes that occurred in human evolution? What was the nature of the phenotypic changes that they expected to explain or illuminate with comparative molecular studies?It has long been understood that the evolution of biological features that do not fossilize, including molecules, can be reconstructed by comparing appropriately chosen species. Human specializations are, by definition, features of the human species that evolved in our lineage after it separated from the lineage leading to chimpanzees and bonobos, our closest relatives. A claim about human specializations requires comparing the human species to its si...

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