Biology subjects

Enard, D.

Publications and source records attributed to Enard, D..

22 records · Page 2Linked to original sources

bioRxiv2019

Viruses rule over adaptation in conserved human proteins

Adaptive evolution often involves fast-evolving proteins, and the fastest-evolving proteins in primates include antiviral proteins engaged in an arms race with viruses 1-3. Even though fast-evolving antiviral proteins are the most studied cases of primate host adaptation against viruses, viruses predominantly interact with host proteins that are broadly conserved between distant species in order to complete their replication cycle 4. Broadly conserved proteins are generally viewed as playing a negligible role in adaptive evolution. Here, we used a dataset of ~4,500 human proteins known to physically interact with viruses (VIPs for Virus-Interacting Proteins), to test the involvement of broadly conserved proteins in adaptive evolution against viruses. We found that VIPs conserved between animals and fungi have experienced not only high rates of adaption, but also strong adaptive events. Broadly conserved proteins that do not interact with viruses experienced very little adaptation. As a result, the arms race with viruses explains more than 75% of adaptation in the most phylogenetically conserved subset of the human proteome. Our results imply that broadly conserved proteins have played a significant role in adaptation, and that viruses were likely one of very few selective pressures that were able to force the conserved, central pillars of host cellular functions to adapt during evolution.

evolutionary biology↗

bioRxiv2018

Exploiting selection at linked sites to infer the rate and strength of adaptation

Genomic data encodes past evolutionary events and has the potential to reveal the strength, rate, and biological drivers of adaptation. However, robust estimation of adaptation rate () and adaptation strength remains a challenging problem because evolutionary processes such as demography, linkage, and non-neutral polymorphism can confound inference. Here, we exploit the influence of background selection to reduce the fixation rate of weakly-beneficial alleles to jointly infer the strength and rate of adaptation. We develop a novel MK-based method (ABC-MK) to infer adaptation rate and strength, and estimate = 0.135 in human protein-coding sequences, 72% of which is contributed by weakly adaptive variants. We show that in this adaptation regime is reduced {approx} 25% by linkage genome-wide. Moreover, we show that virus-interacting proteins (VIPs) undergo adaptation that is both stronger and nearly twice as frequent as the genome average ( = 0.224, 56% due to strongly-beneficial alleles). Our results suggest that while most adaptation in human proteins is weakly-beneficial, adaptation to viruses is often strongly-beneficial. Our method provides a robust framework for estimating adaptation rate and strength across species.

evolutionary biology↗

bioRxiv2017

RNA viruses drove adaptive introgressions between Neanderthals and modern humans

Neanderthals and modern humans came in contact with each other and interbred at least twice in the past 100,000 years. Such contact and interbreeding likely led both to the transmission of viruses novel to either species and to the exchange of adaptive alleles that provided resistance against the same viruses. Here, we show that viruses were responsible for dozens of adaptive introgressions between Neanderthals and modern humans. We identify RNA viruses--specifically lentiviruses and orthomyxoviruses--as likely drivers of introgressions from Neanderthals to Europeans. Our results imply that many introgressions between Neanderthals and modern humans were adaptive, and that host genetic variation can be used to understand ancient viral epidemics, potentially providing important insights regarding current and future epidemics.\n\nOne Sentence SummaryOnce out of Africa, modern humans inherited from Neanderthals dozens of genes already adapted against viruses present in their new environment.

evolutionary biology↗

bioRxiv2016

Pervasive adaptation in Plasmodium-interacting proteins in mammals

The protozoan genus Plasmodium causes malaria in dozens of mammal species, including humans, non-human primates, rodents, and bats. In humans, Plasmodium infections have caused hundreds of millions of documented deaths, imposing strong selection on certain populations and driving the emergence of several resistance alleles. Over the deep timescale of mammalian evolution, however, little is known about host adaptation to Plasmodium. In this work, we expand the collection of known Plasmodium-interacting-proteins (PIPs) in mammalian hosts from ~10 to 410, by manually curating thousands of scientific abstracts. We use comparative tests of adaptation to show that PIPs have experienced >3 times more positive selection than similar mammalian proteins, consistent with Plasmodium as a major and long-standing selective pressure. PIP adaptation is strongly linked to gene expression in the blood, liver, and lung, all of which are clinically relevant tissues in Plasmodium infection. Interestingly, we find that PIPs with immune functions are especially enriched for additional interactions with viruses or bacteria, which together drive a 3.7-fold excess of adaptation. These pleiotropic interactions with unrelated pathogens, along with pressure from other Plasmodium-like Apicomplexan parasites, may help explain the PIP adaptation we observe in all clades of the mammalian tree. As a case study, we also show that alpha-spectrin, the major membrane component of mammalian red blood cells, has experienced accelerated adaptation in domains known to interact specifically with Plasmodium proteins. Similar interactions with Plasmodium-like parasites appear to have driven substantial adaptation in hundreds of host proteins throughout mammalian evolution.

evolutionary biology↗