First paper from our lab – Ancient deletions strike again and mysterious ways of adaptive forces

We have our first paper from the Buffalo laboratory published at Molecular Biology and Evolution (link here, it is Open Access). The paper describes polymorphic human deletions that are shared with Neandertals or Denisovans. Most of these deletions are not introgressed from ancient hominins, but rather have been lingering around since before Human/Neandertal/Denisovan ancestor. As expected majority of these ancient deletions are evolving under neutral conditions and are yet to be drifted away or got fixed. A small percentage of these deletions, however, may have important functions and the fact that they have not been fixed (or eliminated) in the population may indicate some sort of an adaptive, maintaining force. Thanks to Charlotte Hsu of our press-office, we have a very nice (I am not biased at all) press-release focusing more on the biomedical implications of our observations. The article is also covered in Discovery News with a slightly embarrassing title.

I am really excited about our current work especially within the context of the revitalized idea that complex forms of balancing selection may be more prevalent than previously appreciated in humans.  The recent papers that I listed below all highlight interesting cases where variation has been maintained in functional regions of the genome for extended amounts of evolutionary time. Almost all of these papers hint an immune system connection and raise the “Red-queen” like framework to explain these observations. I believe that there may be a very nice angle into susceptibly to autoimmune system diseases involving these variants. Here are the papers:

Leffler et al. http://bit.ly/1L3lxPS  – The paper that made me think about this issue within the context of structural variants)

Cagliani et al. http://bit.ly/1CG5t0s (This is just published also in MBE along with our paper)

Teixeira et al. http://bit.ly/1yJEAd2 (Always good to read from Aida Andrés)

Overall, based on ongoing work in our laboratory and other excellent work that is being conducted elsewhere, I am now convinced that the adaptive forces acting on structural variants (such as deletions described here) are not straightforward, classical sweeps. Instead more complex adaptive forces may be more relevant here. I guess, this is also true for most single nucleotide variants, as well as exemplified by this paper.

It is a very exciting time for studying evolution of structural variants. We can finally leverage ancient genomes to understand the adaptive forces that shape the still mostly enigmatic deletions and duplications that differentiate our genomes.

– Just realized, PJ et al.  just published a paper on a similar premise. 🙂

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