NDLI: Computing how we became human

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Computing how we became human

Content Provider	ACM Digital Library
Author	Haussler, David
Abstract	With our ability to sequence entire genomes, we have for the first time the opportunity to compare the genomes of present day species, and deduce the trajectories by which they diversified from a common ancestral genome. For example, starting with a small shrew-like ancestor in the Cretaceous period about 100 million years ago, the different species of placental mammals radiated outward, creating a stunning diversity of forms from whales to armadillos to humans. From the genomes of present-day species, it is possible to computationally reconstruct what most of the DNA bases in the genome of the common ancestor of placental mammals must have looked like, and deduce most of the changes that lead to humans. In so doing, we discover how Darwinian evolution has shaped us at the molecular level. Because most random mutations to functionally important regions of DNA reduce fitness, these changes usually disappear over time, in a process known as negative selection. From its unusually high conservation between species, it is immediately evident that at least 5% of the human genome has been under negative selection during most of mammalian evolution, and is hence likely to be functionally important. Protein-coding genes and structural RNA genes stand out among the negatively selected regions because of their distinctive pattern of restricted DNA base substitutions, insertions and deletions. However, most of the DNA under negative selection in mammalian genomes, and indeed in vertebrate genomes in general, does not appear to be part of protein-coding or structural RNA genes, and shares no sequence similarity with any DNA in the genomes of invertebrates. Experimental evidence suggests that many of these unclassified vertebrate-conserved DNA elements serve to regulate genes involved in embryonic development. A significant amount of this material appears to have been put into place by the movement of transposons, mobile DNA elements that are derived from ancient viruses, the remnants of which constitute at least half of our genome. This provides new evidence for older theories of McClintock and later Britten and Davidson that mobile DNA elements played a significant role in the evolution of plant and animal gene regulatory networks. Overlaid on the background of negative selection, we occasionally see a short segment of DNA that has changed rapidly in a particular lineage, suggesting possible positive selection for a modified function in that lineage. The most dramatic example of this in the last 5 million years of human evolution occurs in a previously unstudied RNA gene expressed in the developing cerebral cortex, known as Human Accelerated Region 1 (HAR1). This gene is turned on only in a select set of neurons, during the time in fetal development when these neurons orchestrate the formation of the substantially larger cortex of the human brain. It will be many years before the biology of such examples is fully understood, but right now we relish the opportunity to get a first peek at the molecular tinkering that transmuted our animal ancestors into humans.
Starting Page	639
Ending Page	640
Page Count	2
File Format	PDF
ISBN	9781605580470
DOI	10.1145/1374376.1374468
Language	English
Publisher	Association for Computing Machinery (ACM)
Publisher Date	2008-05-17
Publisher Place	New York
Access Restriction	Subscribed
Subject Keyword	Transposons Selection Mammalian evolution Genomes
Content Type	Text
Resource Type	Article

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