A Molecular Investigation of Human Self-Domestication

Did humans tame themselves? One hypothesis put forward to explain humans’ high degree of sociality and engagement in cooperation is the neural crest domestication syndrome (NCDS), which states that traits associated with domestication are linked to a reduction of neural crest cells during development. The author of this review, A Molecular Investigation of Human Self-Domestication, discusses the experiments done by Zanella et al., which uncover the potential link between domestication in humans and Williams-Beuren syndrome (WBS), a disorder characterized by reduction of facial bone size and hypersociality.

Individuals with WBS have a 1.8Mb hemizygous deletion of 7q.ll.23, which includes the loss of BAZ1B, a gene that influences neural crest cell migration and craniofacial development. Zanella et al. found that when AMH genomes are compared to those of archaic hominins, including Denisovans and Neanderthals, AMHs have fixed mutations in the BAZ1B gene that likely result in some loss of function. Presumably, a decrease in BAZ1B expression would lead to reduction in facial bone size, a trait that is observed in the more gracile AMHs as well as other domesticated species. Taken together, these data suggest that a reduction of BAZ1B expression could have played a role in domestication and craniofacial phenotypes in AMHs.

Facial Phenotype Resulting from a Reduction in BAZ1B Expression

Left face shows craniofacial characteristics of AMH with WBS

Right face shows craniofacial characteristics of typical AMH

Link to Papers: https://www.cell.com/trends/genetics/fulltext/S0168-9525(20)30004-4

                         https://advances.sciencemag.org/content/5/12/eaaw7908

Elaine Miller – Trends in Genetics Post 1

Imprint of Assortative Mating on the Human Genome

My husband is short and so am I. Sometimes, an individual will pick a partner that resembles him/herself in various traits (assortative mating). The authors of this paper, Imprint of Assortative Mating on the Human Genome, apply a novel method to detect assortative mating in the human genome. They determined genetic predictors of various traits from SNPs on even-numbered and odd-numbered chromosomes and then computed the correlation between the predictors on the even-numbered chromosomes and odd-numbered chromosomes (θ). The authors present genetic evidence that humans engage in assortative mating for at least two traits: height and level of education.

Correlations between Mates for Genetic Predictors of Height & Level of Education

The authors reasoned that after many generations of assortative mating, the population would reach an equilibrium in which r_m = ~2θ.

x-axis – estimate of θ, measurement of assortative mating in parental generation

y-axis – estimate of r_m, measurement of assortative mating in current generation

Link to Paper: https://www.nature.com/articles/s41562-018-0476-3

Elaine Miller - Potluck 2/4/2020

Genomic Analysis in the Age of Human Genome Sequencing - Potluck 2/4/20

Tuuli Lappalainen, Alexandra J. Scott, Margot Brandt, and Ira M. Hall

March 21, 2019

The authors systematically explain the advances in genome sequencing over the years, highlighting the millions of whole human genomes we will soon have sequenced, while warning geneticists, clinicians, and the public that there are still many limitations to genome sequencing and its link to clinical efforts. While WGS studies are common, many iterations with high coverage must be done in order to separate mutations from sequencing errors. About 8.5% of the genome is difficult to sequence due to indels and high-copy repeats that easily cause misalignments and sequencing errors. This is important clinically since there have been multi-copy genes identified in these regions that have detrimental affects on individuals with mutations or varying amount of copies. A similar problem with sequencing structural variants (SVs) is noted, with a high percentage of sequencing error while accounting for 4-12% of high-impact coding alleles despite only making up 0.2% of total variants. High-read sequencing is still expensive and has a high error rate of up to 10% but there has been some promising progress towards methods that will increase the read length and decrease the cost as well as the error rate. The authors also warn against assumptions made about comparisons with the reference genome, stating that local ancestry estimates are more accurate for individuals whose genome sequence more closely matches the reference genome than those who do not. In the future, the authors hope that methodology will advance with functional annotation being able to identify developmental and environmental effects on cell type and regulatory elements. The authors state that we have made much progress in genome sequencing over the years but we still have a long way to go in making the methods cheaper, more widely used across the globe, error-free, and inclusive.

-Alexis Williams, Potluck 2/4/20

Link: https://doi.org/10.1016/j.cell.2019.02.032

https://www-sciencedirect-com.proxygw.wrlc.org/science/article/pii/S0092867419302156

Week 3: The Human Genome - Africans carry surprising amount of Neanderthal DNA

As members of Homo sapiens spread from Africa into Eurasia some 70,000 years ago, they met and mingled with Neanderthals. Researchers knew that later back-migrations of Europeans had introduced a bit of Neanderthal DNA into African populations, but previous work suggested it was a just a smidgen. In contrast, modern Europeans and East Asians apparently inherited about 2% of their DNA from Neanderthals

Previous efforts simply assumed that Africans largely lacked Neanderthal DNA. The researchers found that African individuals on average had significantly more Neanderthal DNA than previously thought—about 17 megabases (Mb) worth, or 0.3% of their genome. They also found signs that a handful of Neanderthal genes may have been selected for after they entered Africans’ genomes, including genes that boost immune function and protect against ultraviolet radiation.

The best fit model for where Africans got all this Neanderthal DNA suggests about half of it came when Europeans—who had Neanderthal DNA from previous matings—migrated back to Africa in the past 20,000 years. The model suggests the rest of the DNA shared by Africans and the Altai Neanderthal might not be Neanderthal at all: Instead, it may be DNA from early modern humans that was simply retained in both Africans and Eurasians—and was picked up by Neanderthals, perhaps when moderns made a failed migration from Africa to the Middle East more than 100,000 years ago.

ONLINE ARTICLE
LITERATURE

Warrenkevin

Adding Diversity to the Human Genome: GenomeAsia 100K Project

Genomic datasets have been criticized for lack of diversity due to an overabundance of European samples compared to non-European samples. The GenomeAsia 100K project was established to help expand current knowledge of genetic diversity, especially as it pertains to Asian populations. The pilot project aims to produce and analyze a dataset of whole genome sequences for 1,739 individuals across 64 different countries. Sampled individuals came from countries such as India, South Korea, Pakistan, Malaysia, and the Philippines, with particular emphasis on populations that have been relatively underrepresented in other projects.

Population genetics studies using this dataset have determined subpopulation split times as well as analyzed differing degrees of Denisovan admixture within south and southeast Asian populations. In the medical field, research suggests that the dataset has promising potential for expanding current knowledge of variants causing genetic-related diseases. For example, 2 unique variants were identified in PMS2--a gene coding for a protein involved in DNA repair--that may link to a higher predisposition for developing cancer. Continued contributions from the GenomeAsia 100K project will hopefully improve our efforts to understand more about human genetic diversity and ability of genomics to inform social, historical, and medical questions.

Audrey Tjahjadi

Link to the original article: https://www.nature.com/articles/s41586-019-1793-z.pdf
Link to the project website: https://genomeasia100k.org/

Epigenetics found in Single-Cell Archaea, not just Eukaryotes

By Maria Groussis

In a study by the University of Nebraska-Lincoln, epigenetics was found in single-celled archaea, meaning that they are not only present in eukaryotes as previously thought. Evidence of epigenetics was found in Sulfolobus solfataricus, a sulfur-eating species that live in the boiling, acidic springs of Yellowstone National Park. Through previous studies where they increased levels of acidity through the years, scientist developed three independent and genetically different strains. These super acid-resistant derived strains were named Crenarchaeota (SARC) and they showed a resistance 178 times greater than that of their Yellowstone ancestors. This heritable acid-resistance trait was believed to be resulted from a mutation, but this later was proven to be a false assumption. By sequencing the genomes of the three strains of SARC (SARC-C, SARC-O, and SARC-I) and comparing it to the parental genome the mutations were found. SARC-C had 5 mutations and SARC-O had 29, while SARC-I had none. This implies SARC-I must have a different non-mutation mechanism. The scientists then disrupted proteins that are thought to control the expression of resistant-relevant genes and left no change in the DNA. This immediately stopped the resistance in future generations. Therefore, it can be concluded that SARC-I has an epigenetic-like mechanism.

This new evidence of Archaea having epigenetics indicates that it is not as relatively ‘new’ thing to the Earth. It also raises the question whether the shared common ancestor of Archaea and Eukaryotes had this mechanism, or did each evolve epigenetics independently through coevolution. This also raises the question if epigenetics is the reason why no known archaea cause disease or are antibiotic like bacteria. This finding could accelerate the study of epigenetics in Humans. The differentiation of eukaryotic cells and the occurrences of cancer makes it difficult to study in eukaryotes, but the simplicity of archaea and the structural similarity to eukaryotes make it easier to study. Using archaea to study epigenetics is also faster and cheaper. This may finally help scientists determine how to reverse epigenetics and learn how to switch it on and off.

https://www.eurekalert.org/pub_releases/2018-12/uon-nit113018.php

https://news.unl.edu/newsrooms/today/article/not-in-the-dna-evolution-sans-mutation-discovered-in-single-celled-archaea/

http://www.pnas.org/content/115/48/12271.full

According to an article titled "Coffee or Tea? The Answer Might Be In Your Genes" written by Nicola Davis, a genetic predisposition to perceiving the bitterness of particular substances is key in our selection of beverages. This study involves two sets of data. The first study shows that particular genetic variants are linked to the strength of perception of different tastes: one specific variant was associated with slightly higher ratings of bitterness for caffeine and another to great bitterness for quinine and a third to greater bitterness for a drug known as propylthiouracil, or prop. The team found people with a greater genetic predisposition to perceiving the bitterness of caffeine drank a little more coffee but an increase perception of the bitterness of quinine and prop were linked to a small reduction in coffee drinking. The team also found that greater perception of the bitterness of prop was linked to a lower chance of being a heavy drinker of alcohol. Their findings also lead to the conclusion that people who prefer to drink tea, drink it as it contains a lower concentration of bitter substances meaning that it might prove more acceptable than coffee to those with a heightened perception of bitterness. It has also been reported that the preference towards tea can be seen as a consequence of abstaining from coffee because our genes might have made coffee a little bitter for our palates to handle.

Nana Evison