Meiotic Genes Are Enriched in Regions of Reduced Archaic Ancestry

Jégou, Bernard; Sankararaman, Sriram; Rolland, Antoine; Reich, David; Chalmel, Frédéric

doi:10.1093/molbev/msx141

Cited by 43 publications

(38 citation statements)

References 39 publications

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“…In most cases, archaic variants were selected against, with regions of higher selective constraint being depleted in archaic ancestry, particular those that are X-linked or contain testis-expressed and meiotic-related genes. 1,2,16 Some studies have also suggested that Neanderthals had a reduced effective population size, 6,7 owing to a prolonged bottleneck or a deeply structured population. 6,17,18 Natural selection in Neanderthals would thus have been less efficient to purge deleterious mutations, 19,20 a large proportion of which were removed from the genome of modern humans following their admixture with Neanderthals.…”

Section: Introductionmentioning

confidence: 99%

Impact and evolutionary determinants of Neanderthal introgression on transcriptional and post-transcriptional regulation

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Rotival

2019

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Archaic admixture is increasingly recognized as an important source of diversity in modern humans, with Neanderthal haplotypes covering 1-3% of the genome of present-day Eurasians. Recent work has shown that archaic introgression has contributed to human phenotypic diversity, mostly through the regulation of gene expression. Yet, the mechanisms through which archaic variants alter gene expression, and the forces driving the introgression landscape at regulatory regions remain elusive. Here, we explored the impact of archaic introgression on transcriptional and post-transcriptional regulation, focusing on promoters and enhancers across 127 different tissues as well as microRNA-mediated regulation.Although miRNAs themselves harbor few archaic variants, we found that some of these variants may have a strong impact on miRNA-mediated gene regulation. Enhancers were by far the regulatory elements most affected by archaic introgression, with one third of the tissues tested presenting significant enrichments. Specifically, we found strong enrichments of archaic variants in adipose-related tissues and primary T cells, even after accounting for various genomic and evolutionary confounders such as recombination rate and background selection. Interestingly, we identified signatures of adaptive introgression at enhancers of some key regulators of adipogenesis, raising the interesting hypothesis of a possible adaptation of early Eurasians to colder climates. Collectively, this study sheds new light onto the mechanisms through which archaic admixture have impacted gene regulation in Eurasians and, more generally, increases our understanding of the contribution of Neanderthals to the regulation of acquired immunity and adipose homeostasis in modern humans.

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Section: Introductionmentioning

confidence: 99%

Impact and evolutionary determinants of Neanderthal introgression on transcriptional and post-transcriptional regulation

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2019

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“…This is also true for the autosomal regions deficient in both Neanderthal and Denisovan ancestries, which contain a significant enrichment of genes transcribed in meiotic germ cells (Jégou et al, 2017). The phenotypic traits and the type of selective regime acting on them are summarized in Figure 2, and their corresponding genomic regions are listed in Supporting Table. Taking into account that there has been strong selection against archaic introgression among protein-coding genes (Fu et al, 2016;Sankararaman et al, 2016;Vernot & Akey, 2014), functional regions contributing to the uniqueness of some modern human traits could be identified if they are strongly depleted of archaic ancestry .…”

Section: Selection Against Introgressed Regions At the Level Of Genommentioning

confidence: 91%

Evolutionary and Medical Consequences of Archaic Introgression into Modern Human Genomes

Dolgova

Lao

2018

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The demographic history of anatomically modern humans (AMH) involves multiple migration events, population extinctions and genetic adaptations. As genome-wide data from complete genome sequencing becomes increasingly abundant and available even from extinct hominins, new insights of the evolutionary history of our species are discovered.It is currently known that AMH introgressed with archaic hominins once they left the African continent. Current out of African human genomes carry fragments of archaic origin. This review focuses on the fitness consequences of archaic interbreeding in current human populations. We discuss new insights and challenges that researchers face when interpreting the potential impact of introgression on fitness and testing hypotheses about the role of selection within the context of health and disease.Keywords: archaic introgression, fitness, natural selection, Neanderthal, Denisova, anatomically modern humans. Peer-reviewed version available at Genes 2018, 9, 358; doi:10.3390/genes9070358 2 Widespread interbreeding between homininsThe demographic history of anatomically modern humans (AMH) is complex, and involves a large number of migrations, genetic admixtures and introgressions, population extinctions and genetic adaptations, which overlap both in time and in space (see Figure 1). Due to this complexity, the evolutionary history of humankind is still far from being fully understood (Nielsen et al., 2017). During the last 30 years, the most accepted demographic scenario for explaining recent evolution of AMH has been the Out of Africa model (OOA). According to this model, AMH evolved in Africa around 100-200 thousands years ago (kya) in East Africa and migrated to the rest of the world. Classical "pure" OOA assumes that admixture with other archaic populations such as Neanderthals or Denisovans, present at the time of the rise of AMH, either did not occur or was negligible (Lalueza-Fox & Gilbert, 2011). Figure 1. Family tree of the four groups of early humans living in Eurasia 50,000 years ago and the inferred gene flow between the groups due to interbreeding (based on Prüfer et al., 2014;Mondal et al., 2016;Hsieh et al., 2016; Medina-Gomez et al., 2017). The direction and estimated magnitude of inferred gene flow events are shown. Branch lengths and timing of gene flows are not scaled. The dashed line indicates that it is uncertain whether Denisovan gene flow into modern humans in mainland Asia occurred directly or via Oceania. Light violet color indicates introgression events from unknown archaic populations (Ghost).However, genomic studies of ancient DNA have revealed that AMH interbred with other hominid lineages, such as Neanderthals and Denisovans, present in Eurasia up to ∼30,000-50,000 years ago Quach & Quintana-Murci, 2017;Vattathil & Akey, 2015 New studies based on current genetic diversity are suggesting that the events of archaic introgression in AMH did occur out of Africa with other hidden "ghost" archaic populations (Mondal et al., 2016). Furthermore, there i...

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“…Two biological explanations have been proposed to explain the dynamics of purifying selection on archaic human tracts. Two studies [22,26] found enrichments for testis-expressed and meiotic genes in regions of low Neanderthal ancestry, as well as significantly lower Neanderthal ancestry in the X-chromosome than in the autosomes. Similar observations have been reported for regions of low Denisovan ancestry as well [23] .…”

Section: Admixture and Purifying Selectionmentioning

confidence: 99%

Something old, something borrowed: Admixture and adaptation in human evolution

Dannemann

Racimo

2018

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Almost a decade ago, the sequencing of ancient DNA from archaic humans -Neanderthals and Denisovans -revealed that modern and archaic humans interbred at least twice during the Pleistocene. The field of human paleogenomics has now turned its attention towards understanding the nature of this genetic legacy in the gene pool of present-day humans. What exactly did modern humans obtain from interbreeding with Neanderthals and Denisovans? Were introgressed genetic material beneficial, neutral or maladaptive? Can differences in phenotypes among present-day human populations be explained by archaic human introgression? These questions are of prime importance for our understanding of recent human evolution, but will require careful computational modeling and extensive functional assays before they can be answered in full. Here, we review the recent literature characterizing introgressed DNA and the likely biological consequences for their modern human carriers. We focus particularly on archaic human haplotypes that were beneficial to modern humans as they expanded across the globe, and on ways to understand how populations harboring these haplotypes evolved over time. Genome-wide patterns of archaic admixtureIn 2010, the first sequenced Neanderthal genome provided evidence for gene flow from Neanderthals into the ancestors of present-day non-Africans, around 50,000-60,000 years ago [1][2][3] . Since then, archaic human genomes have yielded ever more insightful discoveries. A few years later, a high coverage genome sequence from a Neanderthal found in the Altai mountains allowed researchers to pin down the proportion of Neanderthal ancestry in non-Africans to be ~2% [4] . In 2017, a second high coverage genome sequence from a Neanderthal in Croatia showed that this individual was more closely related to the introgressing Neanderthal population than the Altai Neanderthal, allowing researchers to detect even slightly higher levels of Neanderthal DNA [5] . In 2018, low-coverage genomes of five additional Neanderthals living between 39,000 and 47,000 years ago allowed a first glimpse at population structure in Neanderthals and showed indications of population turnover in late Neanderthal history [6] . But admixture between different human groups has not been limited to modern humans and Neanderthals. The genome sequence of a previously unknown group, the Denisovans (a sister group to Neanderthals), also contributed to the genomes of present-day people in Oceania, and, to a lower extent, to mainland East and South Asians [7][8][9][10][11][12] . Further admixture episodes have also been suggested, including gene flow from an unsampled "super-archaic" human group into Denisovans [4] , from eastern Neanderthals into Denisovans [4] and from modern humans into Neanderthals [13] (Figure 1). While the signals of shared ancestry between modern and archaic human groups are quite evident, the exact processes by which introgression occurred remain unclear. For example, higher levels of Neanderthal ancestry have been observed in...

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Meiotic Genes Are Enriched in Regions of Reduced Archaic Ancestry

Cited by 43 publications

References 39 publications

Impact and evolutionary determinants of Neanderthal introgression on transcriptional and post-transcriptional regulation

Impact and evolutionary determinants of Neanderthal introgression on transcriptional and post-transcriptional regulation

Evolutionary and Medical Consequences of Archaic Introgression into Modern Human Genomes

Something old, something borrowed: Admixture and adaptation in human evolution

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