What are Genetic Markers? 75,000 Genetic Makers Decoded in southern India and Sri Lanka

Amazing stuff!

"75,000 markers decoded: Genetic roots of ancient Tamils unveiled. Human DNA analysis of samples collected from Keeladi and Adichanallur in Tamil Nadu shows that the inhabitants share close genetic proximity to South Indian, Sri Lankan Tamil, and South Asian ancestries. Keeladi archaeological excavation process."

(965) What are Genetic Markers? 75,000 Genetic Makers Decoded | WION News - YouTube

Massive Ancient-DNA Study Reveals Natural Selection Has Accelerated in Recent Human Evolution

Amazing stuff!

"At a glance

• Applying new analytic methods to nearly 16,000 ancient genomes reveals natural selection has acted on hundreds, not dozens, of genes in West Eurasia over the last 10,000 years.
• More than half of the genes have known links to disease risk and other traits today, although it’s not yet clear what made each gene advantageous in prehistoric contexts.
• The work demonstrates the power of ancient DNA to illuminate human biology and medicine in addition to history.

A massive study of ancient DNA from nearly 16,000 people across more than 10,000 years in West Eurasia reveals that natural selection has shaped modern human genomes far more than previously thought. ...

Combining an unprecedented amount of ancient genomic data with novel computational methods, the new analysis shows instead that directional selection has driven the spread or decline of hundreds of gene variants in West Eurasia since the end of the Ice Age and that selection has actually accelerated since people transitioned from hunting and gathering to farming. ...

Since 2010, when the first genome-wide data was recovered from ancient human remains, ancient-DNA research has expanded understanding of the relationships among people living in different time periods and regions of the world.

But geneticists struggled to realize the technology’s promise to illuminate how natural selection has shaped human genetic variation even over the last 10,000 years, when there is enough well-preserved genetic material to support large-scale studies.

The new study broke through that barrier using two innovations.

First, the Reich Lab spent seven years building a collection of DNA sequences from ancient people living in West Eurasia — what is now Europe and parts of the Middle East — that would be comprehensive enough in size and time span to support the work. ...

The lab collaborated with more than 250 archeologists and anthropologists to report new DNA data from 10,016 ancient individuals from West Eurasia. They added those to another 5,820 published ancient sequences and 6,438 modern ones.

“This single paper doubles the size of the ancient human DNA literature,” ...

The second innovation — and even more important to the success of the study, ...  development of computational methods to isolate the signal of directional selection from other causes of gene frequency changes, such as human migration, population mixing, and random genetic fluctuations that occur in small populations. ..."

From the abstract:

"Ancient DNA has transformed our understanding of population history, but its potential to reveal as much about human evolutionary biology has not been realized because of limited sample sizes and the difficulty of distinguishing sustained rises in allele frequency increasing fitness—directional selection—from shifts due to migrations, population structure, or non-adaptive purifying or stabilizing selection.

Here we present a method for detecting directional selection in ancient DNA time-series data that tests for consistent trends in allele frequency change over time, and apply it to 15,836 West Eurasians (10,016 with new data).

Previous work has shown that classic hard sweeps driving advantageous mutations to fixation have been rare over the broad span of human evolution.

By contrast, in the past ten millennia, we find that many hundreds of alleles have been affected by strong directional selection.

We also document one-standard-deviation changes on the scale of modern variation in combinations of alleles that today predict complex traits. This includes decreases in predicted body fat and schizophrenia, and increases in measures of cognitive performance. These effects were measured in industrialized societies, and it remains unclear how these relate to phenotypes that were adaptive in the past. We estimate selection coefficients at 9.7 million variants, enabling study of how Darwinian forces couple to allelic effects and shape the genetic architecture of complex traits."

Massive Ancient-DNA Study Reveals Natural Selection Has Accelerated in Recent Human Evolution | Harvard Medical School (Caveat: I did not read the entire, long article) "Hundreds of genes selected in West Eurasia since farming began, many linked to health"

Ancient DNA reveals pervasive directional selection across West Eurasia (no public access)

Woolly rhino genome recovered from Ice Age wolf stomach

What a headline! A stomach churner! 😊

"Researchers from the Center for Paleogenetics have managed to analyze the genome from a 14,400-year-old woolly rhinoceros, recovered from a tissue sample found preserved inside the stomach of an ancient wolf.

The study, published in Genome Biology and Evolution, shows that woolly rhinos remained genetically healthy until the end of the last Ice Age. The species therefore probably died out due to a rapid collapse of the population, rather than a slow demographic decline. ..."

From the abstract:

"Using temporarily spaced high-coverage ancient genomes, we can assess population decline prior to extinction. However, finding suitable ancient remains for recovering this type of data is challenging.

Here, we sequenced a high-coverage genome from muscle tissue of a 14,400-year-old woolly rhinoceros (Coelodonta antiquitatis)—a cold-adapted herbivore that went extinct ∼14,000-years ago—found inside a permafrost-preserved wolf's stomach.

We compared genome-wide diversity, inbreeding, genetic load, and population size changes in this sample with two other Late Pleistocene Siberian woolly rhinoceros. We found no evidence of population size decline, nor any genomic erosion, shortly prior to the species' demise. Given the few long homozygous segments, typically indicative of recent inbreeding, we infer a stable population size only a few centuries before extinction.

Thus, the woolly rhinoceros' extinction likely happened rapidly, during the Bølling–Allerød interstadial. This study demonstrates the ability to recover high-quality DNA from unlikely sources to elucidate species' extinction dynamics."

Woolly rhino genome recovered from Ice Age wolf stomach

Genome Shows no Recent Inbreeding in Near-Extinction Woolly Rhinoceros Sample Found in Ancient Wolf's Stomach (open access)

The Tumat-1 wolf puppy. Location: Vienna, Austria. Date: 2018

Fig. 1.Sample locations in northeast Siberia.

Origins of THC, CBD and CBC in cannabis revealed by resurrecting extinct ancestral enzymes active millions of years ago

Amazing stuff! Reconstructing extinct enzymes could have wide ranging applications in the future.

"... Researchers ... have experimentally demonstrated for the first time how cannabis acquired the ability to produce these cannabinoids. In the process, they also developed enzymes that show promise for the biotechnological production of cannabinoids for medicinal applications. ...

the researchers reconstructed extinct enzymes that were active millions of years ago in ancestors of the cannabis plant. In cannabis, enzymes play a key role in the production of cannabinoids—bioactive compounds with, among other things, medicinal potential. ..."

"... The researchers used a technique known as ancestral sequence reconstruction. Based on DNA from modern plants, this method makes it possible to infer what enzymes looked like millions of years ago. These ‘ancestral enzymes’ were then resurrected in the laboratory and experimentally tested. The study provides the first experimental evidence that the biosynthesis of cannabinoids such as THC originated within a relatively recent ancestor of cannabis and subsequently became increasingly refined. ..."

From the abstract:

"Cannabinoids, such as tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA) and cannabichromenic acid (CBCA), are bioactive and medicinally relevant compounds found in the cannabis plant (Cannabis sativa L.).

These three compounds are synthesised from a single precursor, cannabigerolic acid (CBGA), through regioselective reactions catalysed by different cannabinoid oxidocyclase enzymes. Despite the importance of cannabinoid oxidocyclases for determining cannabis chemotype and properties, the functional evolution and molecular mechanism of this enzyme family remain poorly understood.

To address this gap, we combined ancestral sequence reconstruction and heterologous expression to resurrect and functionally characterise three ancestral cannabinoid oxidocyclases.

Results showed that the ability to metabolise CBGA originated in a recent ancestor of cannabis and that early cannabinoid oxidocyclases were promiscuous enzymes producing all three THCA, CBDA and CBCA.

Gene duplication and diversification later facilitated enzyme sub functionalisation, leading to extant, highly-specialised THCA and CBDA synthases.

Through rational engineering of these ancestors, we designed hybrid enzymes which allowed identifying key amino acid mutations underlying the functional evolution of cannabinoid oxidocyclases.

Ancestral and hybrid enzymes also displayed unique activities and proved to be easier to produce heterologously than their extant counterparts.

Overall, this study contributes to understanding the origin, evolution and molecular mechanism of cannabinoid oxidocyclases, which opens new perspectives for breeding, biotechnological and medicinal applications."

Origins of THC, CBD and CBC in cannabis revealed

Origins of THC, CBD and CBC in cannabis revealed (original news release) "Where do the well-known cannabis compounds THC, CBD and CBC come from? Researchers ... have experimentally demonstrated for the first time how cannabis acquired the ability to produce these cannabinoids. In the process, they also developed enzymes that show promise for the biotechnological production of cannabinoids for medicinal applications."

Resurrected Ancestral Cannabis Enzymes Unveil the Origin and Functional Evolution of Cannabinoid Synthases (open access)

Fig. 5 Major modifications in the substrate binding region of ancestral and hybrid cannabinoid oxidocyclases.

Pre-Neolithic hunter-gatherer DNA may explain why some people live to 100 years or more

Amazing stuff! So it is not olive oil and mediterranean cuisine? Just kidding!

"... A new study ... found that Italian centenarians carry a higher proportion of genetic material from Western Hunter-Gatherers (WHG) compared to the general population. ..."

From the abstract:

"The genetics of human longevity has been primarily studied using classical methods developed in genome-wide association studies.

With the recent advances in paleogenomics, it is now possible to investigate to what extent ancient population ancestries contribute to complex traits.

In this study, we explored the role of ancient genetic components in human longevity by focusing on the Italian Peninsula, whose genetic heritage includes several past genetic ancestries that have contributed to the current European genetic make-up.

We analyzed genome-wide data of 333 Italian centenarians and 690 geographically matched healthy controls, and compared their genetic composition to 103 ancient genomes representative of the main past European population ancestries.

Our findings indicate that Italian centenarians have a higher genetic affinity with Western Hunter-Gatherer (WHG)-related ancestry compared to controls, according to PCA and f4-statistics.

Logistic regression models based on supervised admixture revealed a significant association between higher WHG ancestry and the centenarian status.

Additionally, residual-based predictive analysis showed that centenarians exhibit a significantly higher WHG contribution independent of the genetic structuring of the general Italian population.

By painting the chromosomes of modern Italians, we also showed a significantly higher number of WHG alleles at pro-longevity SNPs.

In the present study, we demonstrate the contribution of ancient genetic components to the longevity phenotype. In particular, we showed a greater contribution from Western Hunter-Gatherer-related ancestry to Italian centenarians, thus suggesting that this pre-Neolithic genetic component, which has been linked to population shifts occurring within Europe after the Last Glacial Maximum, could be beneficial for longevity today."

Ancient hunter-gatherer DNA may explain why some people live to 100 years or more

Western Hunter-Gatherer genetic ancestry contributes to human longevity in the Italian population (open access)

Fig. 2 Results of the PCA projection analysis.
A Scatterplot with genetic components of 333 CENT, 690 ITA, and selected ancient individuals from the four basal ancient ancestral groups (47 WHG, 14 Iran_N/CHG, 26 Turkey_N, and 16 Yamnaya_EBA) projected onto the modern Euro-Mediterranean reference space.
B Boxplots displaying the distribution of Euclidean distances between CENT or ITA individuals and the centroid of each of the four considered ancestral groups