This is the blog for GW students taking Human Evolutionary Genetics. This site is for posting interesting tidbits on: the patterns and processes of human genetic variation;human origins and migration; molecular adaptations to environment, lifestyle and disease; ancient and forensic DNA analyses; and genealogical reconstructions.

GWHEG figure

GWHEG figure

Thursday, January 21, 2021

Genetic variants from Neanderthals associated with increased (and decreased!?) risk of severe covid


Headlines like this one in the Daily Mail last week seem to contractive headlines from last summer... 

Both studies examined whether genetic variants shared with Neanderthals are associated with an increased risk of covid infection and severity.  And it seems some loci are... with others are associated with a decreased risk. These contradictory results aren't really that surprising as many different genetic factors (and environmental factors) are likely to influence risk.

Note: the study gaining press this month has not yet been published as a peer-reviewed article, but the early study was published in Nature last year.

-posted by Brenda Bradley

Tuesday, January 19, 2021

Dire Wolves were real -- and their genome has been sequenced!


An article in the New York Times last week summarizes results from the first genomic sequencing of dire wolves, recently published in Nature.

The most interesting findings are: (1) they are not as previously assumed a sister species of wolves, but instead represent a deep - now extinct - canid lineage; and (2) unlike other candids, they didn't seem to interbreed with other taxa... which might have contributed to their extinction?

No dragon genomes yet.

Thursday, April 30, 2020

The somatic mutation landscape of the human body

In this paper, scientists used transcriptome data from over 7,500 tissue samples and 36 tissue types to create a catalog of human somatic mutations. Their catalog contains over 280,000 mutations in total and illustrates a number of tissue-specific mutations.

"Tissues that have more mutations than expected from sequencing depth include those most often exposed to environmental mutagens or with a high cellular turnover like the skin, lung, blood, esophagus mucosa, spleen, liver, and small intestine (Fig. 2a). On the other end of the spectrum are those with low environmental exposure or low cellular turnover such as the brain, adrenal gland, prostate, and several types of muscle—heart, esophagus muscularis, and skeletal muscle."

They also found age was correlated with mutation levels across most tissues. Blood showed the highest association with age and sun-exposed skin had the most significant association with C>T mutations commonly associated with UV radiation. They also found higher levels of mutations in female breast tissue compared to men.

Importantly, they also observed that cancer mutations are enriched in non-diseased tissues, which leads them to say these genes are evolving under positive selection and these mutations increased cellular proliferation even before cancer is observed.

Zac Truesdell - Journal update - Genome Biology - 5

The Deep Genome Project

Mice are often used as an organism to study human disease, due to the high number of orthologous genes. Genomic studies over the decades have been able to computationally predict and annotate a large number of genes. However, according to the authors, "more than 75 to 80% of the computationally annotated ~ 20,000 genes in the human genome have not had variation in them tied to any specific phenotype."

To fill in this gap between genotype and phenotype, the authors call for the establishment of an ambitious "Deep Genome Project" to sort of be the spiritual successor to the Human Genome Project (which, as we learned in class, still left a lot of biological questions unanswered).

"The implementation of a Deep Genome Project—to deliver the functional biological annotation of all human orthologous genomic elements in mice—is an essential and executable strategy to transform our understanding of genetic and genomic variation in human health and disease that will catalyze delivery of the promised benefits of genomic medicine to children and adults around the world."

Zac Truesdell - Journal update - Genome Biology - 4

Longitudinal survey of microbiome associated with particulate matter in a megacity

Smog and particulate matter in the air can have major health impacts. Often, we only think about how the chemical compounds of air pollution effect us, but particulate matter also serves as an environment for bacteria to thrive. This study examines the composition of the airborne bacterial community in Beijing over a 6 month period.

Overall, the bacterial community was relatively similar at both high and low particulate matter size. However, it seems that when the air is heavily polluted, larger particulate matter allows for higher levels of bacteria. If I'm understanding the paper correctly, basically the larger particulate matter sizes give more surface area for the bacteria, and also allow interactions between the bacteria species, such as horizontal gene transfer.

So, next time you take a breath of fresh city air, remember it has bacteria from human, dog, and mouse feces floating around in it.

Zac Truesdell - Journal update - Genome Biology - 3

Functional consequences of archaic introgression and their impact on fitness

In this paper, the authors discuss the positive and negative effects on fitness caused by admixture with Neanderthals and Denisovans.

The lower frequency of archaic ancestry on the X chromosome and near testis-expressed genes suggests that first-generation hybrids had high levels of infertility. Additionally, loci associated with neurological and psychiatric disorders have higher levels of archaic haplotypes, suggesting deleterious effects of archaic admixture.

Some results of archaic admixture were positive--including genes associated with skin pigmentation and metabolism. These alleles would have allowed ancient humans to adapt to different climatic regions more rapidly. Some Neanderthal alleles related to immune function have also led to positive adaptations in humans.

Zac Truesdell - Journal update - Genome Biology - 2

CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma

I think I forgot to post a potluck article during the CRISPR discussion week, so here is something interesting.

Long non-coding RNAs (lncRNA) have highly-specific expression in different cell types, giving them potential to be used for targeting specific types of cancer. However, very few lncRNAs have been studied or tested for these purposes yet.

Researchers in this paper used CRISPR interference to screen lncRNA loci on human glioblastoma cells. In class we talked about how CRISPR can be used to edit genomes, but it seems it can also be used to screen for gene function.

Through this method, they identified a number of lncRNA Glioma Radiation Sensitizers (lncGRS). Targeting of lncGRS inhibit growth of glioma cells (brain tumors), but not normal brain cells.

Zac Truesdell - CRISPR potluck/Journal update - Genome Biology