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A parsimonious neutral model suggests Neanderthal replacement was determined by migration and random species drift.

ABSTRACT: Most hypotheses in the heated debate about the Neanderthals' replacement by modern humans highlight the role of environmental pressures or attribute the Neanderthals' demise to competition with modern humans, who occupied the same ecological niche. The latter assume that modern humans benefited from some selective advantage over Neanderthals, which led to the their extinction. Here we show that a scenario of migration and selectively neutral species drift predicts the Neanderthals' replacement. Our model offers a parsimonious alternative to those that invoke external factors or selective advantage, and represents a null hypothesis for assessing such alternatives. For a wide range of parameters, this hypothesis cannot be rejected. Moreover, we suggest that although selection and environmental factors may or may not have played a role in the inter-species dynamics of Neanderthals and modern humans, the eventual replacement of the Neanderthals was determined by the repeated migration of modern humans from Africa into Eurasia.

SUBMITTER: Kolodny O

PROVIDER: S-EPMC5717005 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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A parsimonious neutral model suggests Neanderthal replacement was determined by migration and random species drift.

Kolodny Oren O Feldman Marcus W MW

Nature communications 20171031 1

Most hypotheses in the heated debate about the Neanderthals' replacement by modern humans highlight the role of environmental pressures or attribute the Neanderthals' demise to competition with modern humans, who occupied the same ecological niche. The latter assume that modern humans benefited from some selective advantage over Neanderthals, which led to the their extinction. Here we show that a scenario of migration and selectively neutral species drift predicts the Neanderthals' replacement. ...[more]

PMID: 29089499

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Project description:Unspecific peroxygenase (UPO) is a highly promiscuous biocatalyst, and its selective mono(per)oxygenase activity makes it useful for many synthetic chemistry applications. Among the broad repertory of library creation methods for directed enzyme evolution, genetic drift allows neutral mutations to be accumulated gradually within a polymorphic network of variants. In this study, we conducted a campaign of genetic drift with UPO in Saccharomyces cerevisiae, so that neutral mutations were simply added and recombined in vivo With low mutational loading and an activity threshold of 45% of the parent's native function, mutant libraries enriched in folded active UPO variants were generated. After only eight rounds of genetic drift and DNA shuffling, we identified an ensemble of 25 neutrally evolved variants with changes in peroxidative and peroxygenative activities, kinetic thermostability, and enhanced tolerance to organic solvents. With an average of 4.6 substitutions introduced per clone, neutral mutations covered approximately 10% of the protein sequence. Accordingly, this study opens new avenues for UPO design by bringing together neutral genetic drift and DNA recombination in vivoIMPORTANCE Fungal peroxygenases resemble the peroxide shunt pathway of cytochrome P450 monoxygenases, performing selective oxyfunctionalizations of unactivated C-H bonds in a broad range of organic compounds. In this study, we combined neutral genetic drift and in vivo DNA shuffling to generate highly functional peroxygenase mutant libraries. The panel of neutrally evolved peroxygenases showed different activity profiles for peroxygenative substrates and improved stability with respect to temperature and the presence of organic cosolvents, making the enzymes valuable blueprints for emerging evolution campaigns. This association of DNA recombination and neutral drift is paving the way for future work in peroxygenase engineering and, from a more general perspective, to any other enzyme system heterologously expressed in S. cerevisiae.

Dataset Information

A parsimonious neutral model suggests Neanderthal replacement was determined by migration and random species drift.

Publications

A parsimonious neutral model suggests Neanderthal replacement was determined by migration and random species drift.

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