The human genome is about 3 billion base pairs long, though only about 1-2% of that make up the 20,000-25,000 protein-coding genes that stretch across 23 chromosomes. Despite the staggering amount of genetic material in human cells, a new study has found that only a small fraction of DNA has actually contributed to the evolutionary fitness of humans since our divergence from chimps 6 million years ago. Brad Gulko of Cornell University is lead author on the paper, which was published in Nature Genetics.
“This paper tackles the deep question of how to identify functional non-coding human genomic material controlling human traits and disease,” Gulko said in a press release.
The discovery was made using a computer model which gauged the evolutionary fitness of genes following the human-chimp divergence. Evolutionary fitness is not like physical fitness; it has to do with reproductive fitness. Organisms who are better adapted to their environment are more likely to successfully reproduce and pass along their genes, contributing to the evolution of the species. The computer was able to tease out which genes were able to confer an advantage within populations.
This is not the first time this subject has been probed. Previously, scientists had tried to examine the number of ways the genomes of humans and chimps had split over the last 6 million years. Another way of searching for genes that had been subjected to pressure was to identify the number of DNA variations between humans.
The method used by Gulko’s team integrated both techniques, and then determined the probability that any given gene contributed to the evolutionary fitness of the species. This number was called the 'fitness consequence' (fitCons) score, and was used to determine how biologically significant the gene has been throughout history. This proved to be much more accurate than previous studies.
“What makes our approach unique is the straightforward combination of DNA biochemistry with recent evolutionary pressures," Gulko continued. "Our method allows other scientists not only to use the results, but to readily understand them.”
The fitCons scores tabulated by the computer model suggest that 4.2–7.5% of nucleotides have influenced human fitness in the last 6 million years, though it’s likely that the true number is closer to 5%. The results also suggest that recent events in our evolutionary history likely haven’t made much of an impact on the human genome.
The vast majority of the genome that shaped human evolution was located in regions responsible for regulating the expression of genes. Thirty-five percent were located in the introns of genes, which are areas that do not code for protein. Fifty-two percent of the evolution-driving genome are located in regulatory regions between genes. Only about 9 percent of the significant DNA changes occurred in genes that code for protein, and these genes are shared with other animals.
This shows that though humans create a lot of the same structures as other animals, they are expressed differently and those differences have been crucial to driving human evolution. For instance, humans and chimps both have a similar density of hair follicles on the body, but human hair is much shorter, finer, and lighter than is found on chimps. This could have been to keep humans cooler as they stood upright and began running, a way to reduce parasites, or perhaps even due to sexual selection.
In the future, the researchers believe they could use the computer model to create targeted treatments for a variety of diseases, including ALS, Alzheimer’s, and MS.
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