Monday, January 28, 2013

Between Us and the Monkeys

In 2012 the genome of the last great ape—the bonobo—was published by a team led by the Max Planck Institute for Evolutionary Anthropology in Leipzig. (1) Together with the chimpanzees, the bonobos are the closest living relatives of humans. The chimpanzee and the bonobo genomes differ from the human genome by about 1.3%. The chimpanzee and bonobo genomes differ by about 0.4% from each other.

The 'junk' difference
In 2011 researchers at the Georgia Institute of Technology (2) determined that the differences between human and chimpanzee genomes were primarily not in the protein-coding genes but in the DNA between genes. These “transposable elements were once considered ‘junk DNA’ with little or no function. Now it appears that they may be one of the major reasons why we are so different from chimpanzees.”

Activity Patterns
On November 6, 2012, Dr. Gilad reported to the American Society of Human Genetics that up to 40% of the differences in the expression or activity patters of genes between humans, chimpanzees and rhesus monkeys can be explained by DNA regulatory mechanisms that determine whether and when genes are transcribed into messenger RNA and translated into proteins. Furthermore, the process involving histones (proteins that control the three-dimensional folding of DNA and gene expression) also differs significantly between the three species.

Transcription Factors
One of the regulatory proteins controlling gene expression is a class of DNA-binding proteins called “transcription factors.” In a recent study, (3) a team with the Lawrence Berkeley National Laboratory and the University of California Berkeley is one of the first to describe on a molecular level how one of these transcription factors (TFIID) functions. The TFIID molecule can exist between two states. If it combines with another TF molecule, its state changes and it is now able to bind to DNA at a specific point, thus controlling gene expression.

Gene Regulation
It has become clear after the sequencing of an ever-growing list of organisms that the complexity of an organism is not related to the number of genes it has—especially since it has become difficult to even determine what a gene is and how it can be counted—but to the complexity of gene regulation. “Although the number of protein coding genes has remained fairly constant throughout metazoan evolution, the number of regulatory DNA elements has increased dramatically,” says Eva Nogales, a biophysicist who led the Berkeley team.

Elementary Building Blocks
In the recent ENCODE studies, it was shown that 80% of the human genome, most of which was previously known as “junk” DNA, is actually involved in some biological role, most likely controlling gene expression. Although differences in protein coding genes exist between species, it is evident that the majority of differences lie in the epigenetic areas of the genome controlling gene regulation and the order and degree of gene expression. Much like a Lego set, evolution seems to have used the same pieces in different combinations as much as possible before having to create something totally new.

1. Prufer, Kay, et al., Nature, 2012; DOI: 10.1038/nature11128
2. Polavarapu, Nalini, et al., Mobile DNA, 2011; 2: 13 DOI 10.1186/1759-8753-2-13
3. Cianfrocco Michael, et al., Cell, 2013; 152 (1-2): 120 DOI: 10:1016/j.cell.2012.12.005