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traject
03-07-2019, 02:21 PM
The first study to empirically test the 'AMH Self Domestication Hypothesis' just came out as a preprint and the results validate the hypothesis with a comparison to archiac hominins. For those unfamiliar with the hypothesis, it asserts that craniofacial changes in anatomically modern humans compared to archaic hominins are the result of the same domestication phenomenon causes similar anatomically changes in domesticated species like dogs or foxes. In fact, given these anatomical changes have been shown by Soviet studies to occur when reduced reactive aggression is selected for, this implies that AMH faced selection for reduced reactive aggression as well. For detailed reference, Richard Wrangham's book The Goodness Paradox (https://www.amazon.com/Goodness-Paradox-Relationship-Violence-Evolution-ebook/dp/B07CRDPM14) compellingly argues for this hypothesis.

In particular, neural crest formation appears to be implicated in the domestication process and it is specifically the gene BAZ1B that the preprint 7q11.23 Syndromes Reveal BAZ1B as a Master Regulator of the Modern Human Face and Validate the Self-Domestication Hypothesis (https://www.biorxiv.org/content/10.1101/570036v1) analyzes.

Abstract:

Symmetrical 7q11.23 dosage alterations cause craniofacial and cognitive/behavioral phenotypes that provide a privileged entry point into the evolution of the modern human face and (pro-) sociality. We undertook a functional dissection of chromatin remodeler BAZ1B in neural crest stem cells (NCSCs) from a uniquely informative cohort of typical and atypical patients harboring 7q11.23 Copy Number Variants (CNVs). Our results reveal a key contribution of BAZ1B to NCSC in vitro induction and migration, coupled with a crucial involvement in neural crest (NC)-specific transcriptional circuits and distal regulation. By intersecting our experimental data with new paleogenetic analyses comparing modern and archaic humans, we uncover a modern-specific enrichment for regulatory changes both in BAZ1B and its experimentally defined downstream targets, thereby providing the first empirical validation of the self-domestication hypothesis and positioning BAZ1B as a master regulator of the modern human face.

Relevant archaic results:

Intersection with paleogenomic datasets uncovers a key evolutionary role for BAZ1B
Mild NC deficits have been put forth as a unifying explanatory framework for the defining features of the so-called domestication syndrome, with BAZ1B listed among the putative underlying genes due to its previously reported role in the NC of model organisms(3, 7, 8). The recent observation that its expression is impacted by domestication-related mobile element insertion (MEI) methylation in gray wolves (9)further supported its role in domestication, offering an intriguing parallel to the paleogenomic results that had detected BAZ1B within the regions of the modern genome reflective of selective sweeps and found it enriched for putatively regulatory mutations in AMHs (12). These convergent lines of enticing evidence notwithstanding, neither the neurocristopathic basis of domestication nor its extension to the evolution of the modern human lineage (i.e., self-domestication) have been empirically tested, hence keeping also BAZ1B-based domestication hypotheses to the theoretical ambit.

Having defined the molecular circuits through which BAZ1B shapes the modern human face, we set out to validate the self-domestication hypothesis and its neurocristopathic basis, carrying out a systematic integrative analysis of the overlaps between our empirically defined BAZ1B dosage-sensitive genes (blue Venn in Fig. 4B ) and a combination of uniquely informative datasets highlighting differences between modern humans and archaics (Neanderthals/Denisovans) and between wild/domesticated pairs of four paradigmatic species (1, 10–12)(represented in Fig. 4A by skulls illustrating the more ‘gracile’ and ‘juvenile’ profile in AMH/dog relative to Neanderthal/wolf visible in the overall shape of the neurocranium, reduced proganthism, browridges and nasal projections). Specifically, as shown in Fig. 4B, these datasets include: i) genes associated with signals of positive selection in the modern branch compared to archaic lineages(purple Venn) (10, 11); ii) genes harboring (nearly) fixed mutations in moderns vs archaics (pink Venn); and iii) genes associated with signals of positive selection in the four paradigmatic domesticated species dog, cat, cattle and horse (1)(orange Venn), to reveal statistically significant overlaps between them and genes associated with signals of positive selection in the modern branch compared to archaic lineages. In turn, the list of genes harboring (nearly) fixed mutations in moderns vs archaics contains three classes: i) genes harboring high frequency changes (12)ii) genes harboring missense mutations (red barplot) and iii) genes enriched for mutations in regulatory regions (green barplot) (data based on (12)) (Fig. 4C). As shown in the barplots, the obviously very limited number of high-quality coverage archaic genomes available results in a much higher number of nearly fixed changes identified in archaics (left/negative side of the plot) versus modern humans (right side) (Fig. 4C), setting a comparatively much higher threshold for the identification of nearly fixed modern changes.

These analyses are visualized in Fig. 4D (and detailed in Tables S1-15) through a matrix that intersects all BAZ1B dosage-dependent genes (partitioned in the two categories of directly and inversely correlated, and ordered across the full range of biological significance and regulatory proximity, from simply differentially expressed genes to bona fide direct targets) with the evolutionary changes underlying domestication and self-domestication, yielding the following key insights (color coded for degree of overlap and marked for significance in hypergeometric tests). First, the most significant pattern obtains at the intersection with the top 10% genes showing an excess of (nearly) fixed mutations in the regulatory regions of modern humans compared to archaics, across both directly and inversely BAZ1B level-dependent genes (Tables S1-14). Importantly, this same category of nearly fixed modern regulatory changes is also the only one that returns a statistically significant overlap with the most stringent core of BAZ1B dosage dependent targets (ie. DEGs whose enhancers are both directly bound by BAZ1B and differentially marked upon its decrease), demonstrating that BAZ1B directly controls, in an exquisitely dosage-dependent manner, this particularly relevant set of genes that underwent regulatory changes in human evolution. Second, the overall strongest overlaps map to the class of genes that are inversely correlated to BAZB levels, which we found to be strongly and specifically enriched for head morphogenesis and NC categories (Fig. 2C), thereby confirming craniofacial morphogenesis as the key domain of functionally relevant overlap between BAZ1B dosage and (self-)domestication changes relevant to the evolution of AMHs. Third, despite the spuriously inflated number of apparently fixed mutations in archaics (12), the overall extent of overlap between genes impacted by BAZ1B dosage and our modern and archaic sets does not reveal significantly more hits for archaics. In fact, globally we found consistently more overlapping genes between the BAZ1B targets and the modern human data, and even no statistically significant overlap for any list of the archaic-specific mutations when crossed against BAZ1B level-directly correlated genes. Finally, the (lower) midface emerges as a particularly salient area of functionally relevant overlap (as illustrated in Fig. 4E and detailed in Table S15), given the specific genes that our analysis unearthed: i) COL11A1, one of the few craniofacial genes highlighted across domestication studies (dog, house sparrow, pig breed) and which lies in a region of the human genome that resisted archaic introgression (10), is associated with Marshall syndrome and was also highlighted in a recent study on regulatory changes that shaped the modern human facial and vocal anatomy (60); ii) XYLT1, one of the 5 genes (along with ACAN, SOX9, COL2A1, and NFIX) that affect lower and midfacial protrusion and are among the top differentially methylated genes compared to archaics (Table S15); and iii) NFIB, which belongs to the same gene family as NFIX and shares some of its functions.

Judith
03-15-2019, 04:52 PM
I don’t understand the biochemistry but the anthropology conclusion of self domestication seems very credible!

Looking at today’s world we need still further reductions in aggressive behaviour.