Wednesday, April 22, 2015

Ominous news for the neutral theory nearly every week now

Ominous news for the neutral theory nearly every week now: Nature paper Nature paper yesterday found endogenous retrovirus (ERV) to be functional. We have a paper last week in Genomics providing experimental evidence for essentially no neutral SNPs "Collective effects of SNPs on transgenerational inheritance in Caenorhabditis elegans and budding yeast.", which provides more evidence for the conclusion we published last year "Scoring the collective effects of SNPs: associations of minor alleles with complex traits in model organisms.

Human endogenous retrovirus (HERV) proviruses comprise a significant part of the human genome, with approximately 98,000 ERV elements and fragments making up nearly 8%. One family, termed HERV-K (HML2), makes up less than 1% of HERV elements but is one of the most studied. 

The paper found HERV-K to be fully functional. By inference via good common sense, the whole ERV class should also be functional, which just needs time and effort to be found out. This inference for the ERV kind sequence is exactly like we consider the protein kind to be all functional. Despite the fact that the functions of probably ~80% of human proteins remain unknown but no one doubts that they have a function because we do know some proteins have functions. So, if one type of ERV has functions, which happens to be the most studied, should it not to be the null hypothesis that all ERVs have functions?

The popgen and molecular evolution field today, mostly made up of people who rarely do any bench work on DNA functions, still considers ~90% of human genome to be neutral junks. But how interesting and dramatic, a big chunk of these junks were turned into gold overnight by one paper!! More interesting and dramatic findings of the same kind are sure to come over and over again within the next two years until all popgen researchers abandon their neutral bandwagon and join their bench colleagues who are nearly all on the functional train since long time ago. 

Abstract of the paper:

Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells
• Edward J. Grow, et al
Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections, and comprise nearly 8% of the human genome1. The most recently acquired human ERV is HERVK(HML-2), which repeatedly infected the primate lineage both before and after the divergence of the human and chimpanzee common ancestor2, 3. Unlike most other human ERVs, HERVK retained multiple copies of intact open reading frames encoding retroviral proteins4. However, HERVK is transcriptionally silenced by the host, with the exception of in certain pathological contexts such as germ-cell tumours, melanoma or human immunodeficiency virus (HIV) infection5, 6, 7. Here we demonstrate that DNA hypomethylation at long terminal repeat elements representing the most recent genomic integrations, together with transactivation by OCT4 (also known as POU5F1), synergistically facilitate HERVK expression. Consequently, HERVK is transcribed during normal human embryogenesis, beginning with embryonic genome activation at the eight-cell stage, continuing through the emergence of epiblast cells in preimplantation blastocysts, and ceasing during human embryonic stem cell derivation from blastocyst outgrowths. Remarkably, we detected HERVK viral-like particles and Gag proteins in human blastocysts, indicating that early human development proceeds in the presence of retroviral products. We further show that overexpression of one such product, the HERVK accessory protein Rec, in a pluripotent cell line is sufficient to increase IFITM1 levels on the cell surface and inhibit viral infection, suggesting at least one mechanism through which HERVK can induce viral restriction pathways in early embryonic cells. Moreover, Rec directly binds a subset of cellular RNAs and modulates their ribosome occupancy, indicating that complex interactions between retroviral proteins and host factors can fine-tune pathways of early human development.

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