Convoluted human evolution: Speedy HARs (Introduction)

by David Turell @, Friday, August 12, 2016, 21:27 (465 days ago) @ David Turell

We have DNA areas that are 'human accelerated regions' which developed our special evolution:

"The chimp genome was published in 2005, when I was a postdoc at the University of California, Santa Cruz, and those of 12 other vertebrates followed shortly thereafter. At the same time, computational scientists were busy developing algorithms to scan DNA for similar regions across multiple species. Such sequence conservation suggests that these areas are responsible for critical functions. I took these comparative genomic scans to the next level by writing a computer program to identify DNA sequences that are conserved in other animals but have changed rapidly in humans since we evolved from our common ancestor with chimpanzees. This evolutionary signature predicts a loss or modification of function in humans. My colleagues and I used this two-part pattern to define the fastest-evolving regions of the human genome, known as human accelerated regions (HARs). We published the first 202 HARs in 2006.

"An exciting but daunting pattern emerged: only a handful of HARs were in genes. In fact, we had no idea what the vast majority of these putatively functional and uniquely human DNA sequences did, let alone their role in human evolution. HARs are short—on average just 227 base pairs long, much smaller than a gene. They looked like what we called “junk DNA” at that time and would not have been at the top of anyone's list of genomic regions to study, if not for their compelling conservation across most animals and notable differences in humans. (my bold)

"...the combined list of identified HARs now includes nearly 3,000 genome segments.4 But the original trend still holds; nearly all HARs are outside genes, some quite far away from any gene in the genome.


"Ignoring human DNA for a moment, HAR regions are some of the most conserved sequences in the genomes of mammals. Some of them are nearly identical between chimpanzee and platypus, for example. This close identity suggests that the information encoded in these sequences is critical, and that changes to the sequences will alter their important instructions. This makes the human mutations in HARs truly unexpected.


"Integrating this new information into computational models, my colleagues and I predicted that about 5 percent of HARs function as noncoding RNAs, while most are enhancers that control gene expression during embryonic development.


"Many HARs are located near genes that control fundamental developmental processes,9 so their altered regulatory function could have profound effects on human biology. Supporting this, the human version of one HAR enhancer (ANC516/HARE5) is active earlier in development and in a larger region of the brain compared to the chimp HAR. Human HARE5 increases expression of its target gene, Frizzled 8, affecting the size and development of the brain in mice.


"For example, by comparing a human HAR sequence with the HAR sequence of an archaic hominin, researchers can estimate if the HAR mutated before, after, or during the time period of our common ancestor.12 This approach has revealed that the rate at which HAR mutations emerged was slightly higher before we split from Neanderthals and Denisovans.3,13 As a result, most HAR mutations are millions of years old and shared with these extinct hominins (but not with chimpanzees). (my bold)

" ...we spent the past decade showing that HARs are key regulators of embryonic development. This is a huge step forward from HARs being viewed as bizarre junk DNA of unknown function. Looking ahead to when all of our genomes have been analyzed and tools exist for precise editing of HARs in human cells, it seems possible to figure out what happened when each of these evolutionarily conserved sequences suddenly mutated in humans."

Comment: This is why we are not chimps. Looks like God dabbled here to create us. Note the disappearance of more 'junk DNA'. Very long instructive article so I skipped the supportive research descriptions.

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