Ancient human DNA in sub-Saharan Africa lifts veil on prehistory

The first large-scale study of ancient human DNA from sub-Saharan Africa opens a long-awaited window into the identity of prehistoric populations in the region and how they moved around and replaced one another over the past 8,000 years.

Mount Hora in Malawi, where the oldest DNA in the study, from a woman who lived more than 8,000 years ago, 
was obtained [Credit: Jessica C. Thompson/Emory University]

The findings, published Cell by an international research team led by Harvard Medical School, answer several longstanding mysteries and uncover surprising details about sub-Saharan African ancestry—including genetic adaptations for a hunter-gatherer lifestyle and the first glimpses of population distribution before farmers and animal herders swept across the continent about 3,000 years ago.

"The last few thousand years were an incredibly rich and formative period that is key to understanding how populations in Africa got to where they are today," said David Reich, professor of genetics at HMS and a senior associate member of the Broad Institute of MIT and Harvard. "Ancestry during this time period is such an unexplored landscape that everything we learned was new."

Reich shares senior authorship of the study with Ron Pinhasi of the University of Vienna and Johannes Krause of the Max Planck Institute for the Science of Human History and the University of Tübingen in Germany.

"Ancient DNA is the only tool we have for characterizing past genomic diversity. It teaches us things we don't know about history from archaeology and linguistics and can help us better understand present-day populations," said Pontus Skoglund, a postdoctoral researcher in the Reich lab and the study's first author. "We need to ensure we use it for the benefit of all populations around the world, perhaps especially Africa, which contains the greatest human genetic diversity in the world but has been underserved by the genomics community."

Long time coming

Although ancient-DNA research has revealed insights into the population histories of many areas of the world, delving into the deep ancestry of African groups wasn't possible until recently because genetic material degrades too rapidly in warm, humid climates.

Technological advances—including the discovery by Pinhasi and colleagues that DNA persists longer in small, dense ear bones—are now beginning to break the climate barrier. Last year, Reich and colleagues used the new techniques to generate the first genome-wide data from the earliest farmers in the Near East, who lived between 8,000 and 12,000 years ago.

Genomic time-lapse

Almost half of the team's samples came from Malawi, providing a series of genomic snapshots from the same location across thousands of years.

This visual abstract depicts the findings of Skoglund et al. In their paper, the prehistory of African populations is explored 
by genome-wide analysis of 16 human remains providing insight into lineages, admixture, and genomicadaptions 
[Credit: Skoglund et al./Cell 2017]

The time-series divulged the existence of an ancient hunter-gatherer population the researchers hadn't expected.

When agriculture spread in Europe and East Asia, farmers and animal herders expanded into new areas and mixed with the hunter-gatherers who lived there. Present-day populations thus inherited DNA from both groups.

The new study found evidence for similar movement and mixing in other parts of Africa, but after farmers reached Malawi, hunter-gatherers seem to have disappeared without contributing any detectable ancestry to the people who live there today.

"It looks like there was a complete population replacement," said Reich. "We haven't seen clear evidence for an event like this anywhere else."

The Malawi snapshots also helped identify a population that spanned from the southern tip of Africa all the way to the equator about 1,400 years ago before fading away. That mysterious group shared ancestry with today's Khoe-San people in southern Africa and left a few DNA traces in people from a group of islands thousands of miles away, off the coast of Tanzania.

"It's amazing to see these populations in the DNA that don't exist anymore," said Reich. "It's clear that gathering additional DNA samples will teach us much more."

"The Khoe-San are such a genetically distinctive people, it was a surprise to find a closely related ancestor so far north just a couple of thousand years ago," Reich added.

The new study also found that West Africans can trace their lineage back to a human ancestor that may have split off from other African populations even earlier than the Khoe-San.

Missing links

The research similarly shed light on the origins of another unique group, the Hadza people of East Africa.

"They have a distinct appearance, language and genetics, and some people speculated that, like the Khoe-San, they might represent a very early diverging group from other African populations," said Reich. "Our study shows that instead, they're somehow in the middle of everything."

The Hadza, according to genomic comparisons, are today more closely related to non-Africans than to other Africans. The researchers hypothesize that the Hadza are direct descendants of the group that migrated out of Africa, and possibly spread within Africa as well, after about 50,000 years ago.

Another discovery lay in wait in East Africa.

Scientists had predicted the existence of an ancient population based on the observation that present-day people in southern Africa share ancestry with people in the Near East. The 3,000-year-old remains of a young girl in Tanzania provided the missing evidence.

Reich and colleagues suspect that the girl belonged to a herding population that contributed significant ancestry to present-day people from Ethiopia and Somalia down to South Africa. The ancient population was about one-third Eurasian, and the researchers were able to further pinpoint that ancestry to the Levant region.

"With this sample in hand, we can now say more about who these people were," said Skoglund.

The finding put one mystery to rest while raising another: Present-day people in the Horn of Africa have additional Near Eastern ancestry that can't be explained by the group to which the young girl belonged.

Natural selection

Finally, the study took a first step in using ancient DNA to understand genetic adaptation in African populations.

It required "squeezing water out of a stone" because the researchers were working with so few ancient samples, said Reich, but Skoglund was able to identify two regions of the genome that appear to have undergone natural selection in southern Africans.

One adaptation increased protection from ultraviolet radiation, which the researchers propose could be related to life in the Kalahari Desert. The other variant was located on genes related to taste buds, which the researchers point out can help people detect poisons in plants.

The researchers hope that their study encourages more investigation into the diverse genetic landscape of human populations in Africa, both past and present. Reich also said he hopes the work reminds people that African history didn't end 50,000 years ago when groups of humans began migrating into the Near East and beyond.

"The late Stone Age in Africa is like a black hole, research-wise," said Reich. "Ancient DNA can address that gap."

Source: Cell Press [September 21, 2017]

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10,000 year-old DNA proves when fish colonized lakes

DNA in lake sediment forms a natural archive displaying when various fish species colonized lakes after the glacial period. This according to researchers at the Department of Ecology and Environmental Science at Umeå University in a study published in the journal Methods in Ecology and Evolution. Their analyses of the prevalence of whitefish DNA in sediment reveal that the whitefish came to Lake Stora Lögdasjön in Västerbotten already 10,000 years ago, whereas Lake Hotagen in Jämtland had its whitefish only 2,200 years ago.

Lake Whitefish [Credit: Northwest Territories Tourism]

"It's fantastic news that DNA can be stored for so long in lake sediment. Normally, free DNA molecules break down within days, but certain DNA fragments are preserved because they bind to clay particles," says Professor Göran Englund, one of the researchers behind the study.

The DNA molecules in lake sediment are few and hard bound to particles. This resulted in challenging analyses and required development of new methods, both for extracting sufficiently clean DNA and for the statistical analysis of data. For this work, doctoral student Fredrik Olajos and researcher Folmer Bokma's efforts were of particular importance.

"Being able to map the prevalence of DNA in lake sediments is now opening up a new window into history, which lets us see how nature has developed over a long period of time," says Göran Englund. We have already started a project aiming to study how lake ecosystems are affected by historical climate changes. That can provide important clues to a better understanding of how the current global warming will affect ecosystems."

Researchers chose Stora Lögdasjön and Hotagen for the study since they expected the whitefish to have colonized these lakes at different points in time. Stora Lögdasjön was connected to the Baltic Sea when the inland ice melted around 10,000 years ago. The connection was cut off 9,200 years ago when the land uplift created a waterfall, Storforsen, which the whitefish was unable to travel up.

"Our hypothesis was that the whitefish colonized Stora Lögdasjön immediately after the ice-melt, which turned out accurate. Close to Hotagen, on the other side, there was a waterfall that prevented the whitefish from colonizing the lake after the ice melted," says Göran Englund.

Historic, written sources, however, show that whitefish has been found in Hotagen at least since the 18th century. Furthermore, the researchers were able to see that the speciation process that occur in many lakes -- namely that whitefish populations diverge into large-bodied and small-bodied species, had not developed as far in Hotagen.

"Based on this information, we assumed that the whitefish had colonized the lake long after ice-melt, but before the 18th century. It happening already 2,200 years ago was, however, a slight surprise," says Göran Englund.

"Naturally, we can't know for certain how the whitefish spread to Hotagen. Fish-eating animals like the otter, bear, osprey and dipper may have been involved, but the most likely theory is that hunters and fishermen who resided in the area 2,000 years ago played a part. We can see increasing evidence that fish species were introduced to new lakes by the humans that first colonized Scandinavia," concludes Göran Englund.

Source: Umeå Universitet [September 20, 2017]

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Complex life evolved out of the chance coupling of small molecules

Complex life, as we know it, started completely by chance, with small strands of molecules linking up, which eventually would have given them the ability to replicate themselves.

A simple RNA molecule such as this may have been responsible for the evolution 
of complex life as we know it [Credit: Wits University]

In this world, billions of years ago, nothing existed that we would recognise today as living. The world contained only lifeless molecules that formed spontaneously through the natural chemical and physical processes on Earth.

However, the moment that small molecules connected and formed larger molecules with the ability to replicate themselves, life started to evolve.

“Life was a chance event, there is no doubt about that,” says Dr Pierre Durand from the Evolution of Complexity Laboratory in the Evolutionary Studies Institute at Wits University, who led a project to find out how exactly these molecules linked up with each other.

Very simple ribonucleic acid (RNA) molecules (compounds similar to Deoxyribonucleic acid (DNA)) can join other RNA molecules to themselves though a chemical reaction called ligation. The random joining together of different pieces or RNA could give rise to a group of molecules able to produce copies of themselves and so kick start the process of life.

While the process that eventually led to the evolution of life took place over a long period of time, and involved a number of steps, Wits PhD student Nisha Dhar and Durand have uncovered how one of these crucial steps may have occurred.

They have demonstrated how small non-living molecules may have given rise to larger molecules that were capable of reproducing themselves. This path to self-replicating molecules was a key event for life to take hold.

“Something needed to happen for these small molecules to interact and form longer, more complex molecules and that happened completely by chance,” says Durand.

These smaller RNA molecules possessed enzyme activity that allowed ligation, which, in turn allowed them to link up with other small molecules thereby forming larger molecules.

“The small molecules are very promiscuous and can join other pieces to themselves. What was interesting was that these smaller molecules were smaller than we had originally thought,” says Durand.

The smallest molecule that exhibited self-ligation activity was a 40-nucleotide RNA. It also demonstrated the greatest functional flexibility as it was more general in the kinds of substrates it ligated to itself although its catalytic efficiency was the lowest.

“Something needed to happen for molecules to reproduce, and thereby starting life as we know it. That something turned out to be the simple ligation of a set of small molecules, billions of years ago,” says Durand.

The study is published in the journal Royal Society Open Science.

Source: Wits University [September 20, 2017]

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New study switches from genetic to metabolic analysis to reconstitute evolutionary process

A new method for analyzing a living being chemical compositions is tested in Andean plants and attest the genesis of species by means of geographic isolation. Scientists analyzed chemical compounds which express specific biogeographic trends in the evolutionary process, validating a Smithsonian hypothesis on the evolution of the genus Espeletia in the process.

A new method for analyzing a living being chemical compositions is tested in Andean plants and attest the genesis 
of species by means of geographic isolation [Credit: Frederico Padilla]

With 72 species currently identified, Espeletia is a plant genus endemic to the paramo, a moist alpine biome unique to the northern Andes. This genus, which inhabits the world's most diverse high-altitude ecosystem, is considered an outstanding example of adaptive success.

Brazilian scientists investigated over Espeletia's diversity and geographic distribution in the paramo; the result, published in Scientific Reports, suggests that researchers might reconstitute more accurately the whole speciation process making use of a relatively unexplored bias in the study of evolutionary science: metabolomics.

Metabolomics refers to an area of study focusing on the chemical substances synthesized by a living organism -- a byproduct of its metabolism -- which is used to map chemical compounds inherent to a given species. In order to do so, a combination of techniques involving plant extracts, geographic data, and multivariate statistics is required. Studies of this kind are usually based on genomics, DNA marker analysis or morphological comparisons.

Researchers at the University of Sao Paulo's School of Pharmaceutical Sciences -- Ribeirao Preto campus (FCFRP-USP), in Brazil, use metabolic fingerprinting for the first time to explain the evolutionary histories and biogeographic characteristics of Espeletia.

"Basically, we took the chemical compositions of the species of Espeletia and their metabolome and found a correlation with their geographic origins. Species present in the same locations display similar chemical profiles. The same link had already been found using molecular markers but on a larger geographic scale. This shows that the geography of the Andes not only determined the evolution of this plant group, and possibly of other plant groups in the region but also shaped the chemical compositions of these species," said Federico Padilla, one of the authors of the article.

Based on a study supported by Sao Paulo Research Foundation (FAPESP) through regular research grant, the article confirms a hypothesis on the origin and migration routes of Espeletia along the northern Andes proposed by researchers at the US National Museum of Natural History, part of the Smithsonian Institution, in the 1990s, which was hitherto partially supported by molecular markers.

According to this hypothesis, the original stock of Espeletia diversified when the first population of the genus started expanding in two directions from the western part of the Cordillera de Merida, the largest massif in Venezuela. One branch moved along the Venezuelan Andes, while the other moved west and southwest along the Colombian Andes and into northern Ecuador.

"Historically, this kind of analysis has been based on molecular markers. However, genetic analysis is unable to determine specific biogeographic trends with satisfactory precisions in groups that have evolved recently, such as the genus Espeletia, for which it merely identifies two groups, the Venezuelan and Colombian species, " Padilla said.

Metabolites data point evolutionary adaptation

The Smithsonian hypothesis was confirmed by an analysis of the secondary metabolites (i.e., the chemical compounds involved in plants' adaptations to the ecosystem), which pointed to patterns of geographic distributions and chemical diversifications in the Andean paramos.

"Each kind of marker has advantages and disadvantages," said Professor Fernando Batista da Costa , Padilla's supervisor and a co-author of the article published in Scientific Reports. "Unlike animals, plants can't move in order to adapt to this or that environment. Instead, they produce a vast array of chemical compounds that help them adapt to the place where they grow."

The rugged topography of the Andes makes the paramo a highly fragmented biome, biologically and geographically comparable to an archipelago in which "islands" of open grassland vegetation are separated by dense forests or deep valleys that prevent plant species from communicating with other paramos.

According to the article, this geographic isolation is a particularly influential factor for species with limited seed dispersal and a lack of long-distance pollinators, as is the case for Espeletia.

"We prove that their isolation favored allopatric speciation, meaning speciation occurring in separate regions because of geographic barriers. Darwin proposed this kind of speciation in his evolutionary theory as a result of his observations in the Galapagos Archipelago. He saw there that different islands had different species and that these species were related to each other," Batista da Costa said.

The researchers' analyses of the chemical compositions showed that species of Espeletia in different paramos differ not only genetically and morphologically but also chemically.

"In each paramo, most species accumulate different chemical compounds that may possibly be linked to their adaptation to that particular geographic area," Padilla said. "We demonstrate, using chemical evidence, that allopatric speciation occurred in these paramos and groups of species, as had been proposed in the 1990s."

Application of metabolomics in other areas

According to the researchers, this approach can be used to study practically all of a plant's metabolites at the same time.

"In classical phytochemistry, we studied one plant at a time and usually identified a few chemical substances," Padilla said. "With the new techniques and equipment, such as the liquid chromatography coupled with mass spectrometry that we used, we can now assemble 100 or more plant extracts, analyze them all at the same time, and obtain a data matrix potentially representing more than 1,000 chemical compounds."

The researchers stress that analogous models to that described in the article can be used to obtain metabolic fingerprints for other plants with the aim of analyzing their biogeographic and evolutionary histories.

"This new model can be used in agriculture, or for medicinal plants, or even by the police, for example, to identify the origin of marijuana consumed in a particular region," said Batista.

Source: Fundação de Amparo à Pesquisa do Estado de São Paulo [September 19, 2017]

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Humans no longer have ancient defence mechanism against viruses

Insects and plants have an important ancient defence mechanism that helps them to fight viruses. This is encoded in their DNA. Scientists have long assumed that vertebrates – including humans – also had this same mechanism. But researchers at KU Leuven have found that vertebrates lost this particular asset in the course of their evolution.

Credit: KU Leuven

The possibilities encoded in our DNA are expressed via RNA. Conversely, RNA interference (RNAi) can also suppress the expression of a specific gene. Insects and plants use this RNAi mechanism to defend themselves against viruses, among other things. With a little help, insects and plants can even be made resistant to certain diseases through this RNAi mechanism. Examples include so-called genetically modified crops.

It seems only logical to assume, then, that humans can be protected against specific diseases in a similar way. However, past experiments to this effect have proven to be a challenge. Researchers from the Animal Physiology and Neurobiology unit at KU Leuven have now shown why this is the case.

KU Leuven researcher Niels Wynant studied Argonaute proteins, which play an important role in the RNAi process. “In a first stage, we compared the DNA of more than 40 living organisms from various important animal groups. It’s the first time that such a diverse group was studied. It didn’t take us long to find the Argonaute proteins in these organisms. We also discovered the existence of three distinct types of Argonautes, each with a specific biological role,” Wynant explains.

Credit: KU Leuven

“Two out of these three types are especially important for our research: AGO1 and AGO2. The AGO1 family plays a role in regulating its own gene expression. These proteins help to determine which characteristics encoded in the DNA are actually expressed. The AGO2 family takes care of the defence against viruses. However, we didn’t find these AGO2 proteins in vertebrates."

The researchers also went back in time by examining the DNA of sponges and cnidarians, two ancient animal species. They found AGO2 proteins in the genome of these animals. Given that vertebrates and humans descend from these organisms, their common ancestor must have had the AGO2 type as well. "We suspect that the AGO2 proteins lost importance when vertebrates started developing a secondary immune system in which antibodies, interferons, and T-cells – rather than Argonaute proteins – fight viruses.”

In a second stage, the researchers examined the speed at which the Argonaute proteins evolved over time. “Argonautes that fight viruses have to be able to evolve very quickly because viruses are constantly adapting as well.” says Niels Wynant. "In invertebrates, we noticed that AGO2 proteins indeed evolved much faster than their AGO1 counterparts. We didn’t see this rapidly evolving group in the vertebrates.”

These findings, published in Scientific Reports, explain for the first time why RNAi is more efficient for fighting diseases in insects than in humans.

Author: Tine Danschutter | Source: KU Leuven [September 15, 2017]

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Why we did not evolve to live forever: Unveiling the mystery of why we age

Researchers at the Institute of Molecular Biology (IMB) in Mainz have made a breakthrough in understanding the origin of the ageing process. They have identified that genes belonging to a process called autophagy – one of the cells most critical survival processes – promote health and fitness in young worms but drive the process of ageing later in life.

Researchers have made a breakthrough in understanding the origin of the ageing process [Credit: Pixabay]

This research published in the journal Genes & Development gives some of the first clear evidence for how the ageing process arises as a quirk of evolution. These findings may also have broader implications for the treatment of neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's disease where autophagy is implicated. The researchers show that by promoting longevity through shutting down autophagy in old worms there is a strong improvement in neuronal and subsequent whole body health.

Getting old, it's something that happens to everyone and nearly every species on this planet, but the question is, should it? In a recent publication in the journal Genes & Development titled "Neuronal inhibition of the autophagy nucleation complex extends lifespan in post-reproductive C. elegans,"  the laboratory of Dr. Holger Richly at IMB, has found some of the first genetic evidence that may put this question to rest.

As Charles Darwin explained, natural selection results in the fittest individuals for a given environment surviving to breed and pass on their genes to the next generation. The more fruitful a trait is at promoting reproductive success, the stronger the selection for that trait will be. In theory, this should give rise to individuals with traits which prevent ageing as their genes could be passed on nearly continuously. Thus, despite the obvious facts to the contrary, from the point of evolution ageing should never have happened.

This evolutionary contradiction has been debated and theorised on since the 1800s. It was only in 1953 with his hypothesis of antagonistic pleiotropy (AP) that George C. Williams gave us a rational explanation for how ageing can arise in a population through evolution. Williams proposed that natural selection enriches genes promoting reproductive success but consequently ignores their negative effects on longevity. Importantly, this is only true when those negative effects occur after the onset of reproduction. Essentially, if a gene mutation results in more offspring but shortens life that's fine. This is because there can be more descendants carrying on the parent's genes in a shorter time to compensate.

Accordingly, over time, these pro-fitness, pro-ageing mutations are actively selected for and the ageing process becomes hard-wired into our DNA. While this theory has been proven mathematically and its implications demonstrated in the real world, actual evidence for genes behaving in such as fashion has been lacking.

This evidence has now arrived according to the co-lead author of the paper Jonathan Byrne, "The evolutionary theory of ageing just explains everything so nicely but it lacked real evidence that it was happening in nature. Evolution becomes blind to the effects of mutations that promote ageing as long as those effects only kick in after reproduction has started. Really, ageing is an evolutionary oversight." Jonathan continues "These AP genes haven't been found before because it's incredibly difficult to work with already old animals, we were the first to figure out how to do this on a large scale." He explains further "From a relatively small screen, we found a surprisingly large number of genes [30] that seem to operate in an antagonistic fashion." Previous studies had found genes that encourage ageing while still being essential for development, but these 30 genes represent some of the first found promoting ageing specifically only in old worms. "Considering we tested only 0.05% of all the genes in a worm this suggests there could be many more of these genes out there to find," says Byrne.

The evidence for ageing driven by evolution was not the only surprise the paper had in store, according to Thomas Wilhelm, the other co-lead author on the paper. "What was most surprising was what processes those genes were involved in." Not content to provide just the missing evidence for a 60-year-old puzzle, Wilhelm and his colleagues went on to describe what a subset of these genes do in C. elegans and how they might be driving the ageing process. "This is where the results really get fascinating," says Dr. Holger Richly, the principal investigator of the study. "We found a series of genes involved in regulating autophagy, which accelerate the ageing process." These results are surprising indeed, the process of autophagy is a critical recycling process in the cell, and is usually required to live a normal full lifetime.

Autophagy is known to become slower with age and the authors of this paper show that it appears to completely deteriorate in older worms. They demonstrate that shutting down key genes in the initiation of the process allows the worms to live longer compared with leaving it running crippled. "This could force us to rethink our ideas about one of the most fundamental processes that exist in a cell," Richly explains. "Autophagy is nearly always thought of as beneficial even if it's barely working. We instead show that there are severe negative consequences when it breaks down and then you are better off bypassing it all together. It's classic AP. In young worms, autophagy is working properly and is essential to reach maturity but after reproduction, it starts to malfunction causing the worms to age,” he continues.

In a final revelation, Richly and his team were able to track the source of the pro longevity signals to a specific tissue, namely the neurons. By inactivating autophagy in the neurons of old worms they were not only able to prolong the worms life but they increased the total health of the worms dramatically. "Imagine reaching the halfway point in your life and getting a drug that leaves you as fit and mobile as someone half your age who you then live longer than, that's what it's like for the worms," says Thomas Wilhelm. "We turn autophagy off only in one tissue and the whole animal gets a boost. The neurons are much healthier in the treated worms and we think this is what keeps the muscles and the rest of the body in good shape. The net result is a 50% extension of life."

While the authors do not yet know the exact mechanism causing the neurons to stay healthier for longer, this finding could have real world implications. "There are many neuronal diseases associated with dysfunctional autophagy such as Alzheimer's, Parkinson's, and Huntington's disease, it is possible that these autophagy genes could represent a good way to help preserve neuronal integrity in these cases," elaborates Thomas Wilhelm. While any such a treatment would be a long way off, assuming such findings could be recapitulated in humans, it does offer a tantalising hope; prevent disease and get younger and healthier while doing it.

Source: Johannes Gutenberg Universitaet Mainz [September 15, 2017]

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Huge genetic diversity among Papuan New Guinean peoples revealed

The first large-scale genetic study of people in Papua New Guinea has shown that different groups within the country are genetically highly different from each other. Scientists at the Wellcome Trust Sanger Institute and their colleagues at the University of Oxford and the Papua New Guinea Institute of Medical Research reveal that the people there have remained genetically independent from Europe and Asia for most of the last 50,000 years, and that people from the country’s isolated highlands region have been completely independent even until the present day.

Traditional Enga cultural show in Wabag, Papua New Guinea 
[Credit: Michal Knitl/Shutterstock]

Reported in the journal Science, the study also gives insights into how the development of agriculture and cultural events such as the Bronze or Iron Age could affect the genetic structure of human societies.

Papua New Guinea is a country in the southwestern Pacific with some of the earliest archaeological evidence of human existence outside Africa. Largely free from Western influence and with fascinating cultural diversity, it has been of enormous interest to anthropologists and other scientists seeking to understand human cultures and evolution.

Male Huli tribe member in Tari area of Papua New Guinea in traditional clothes and face paint 
[Credit: Amy Nichole Harris/Shutterstock]

With approximately 850 domestic languages, which account for over 10 per cent of the world’s total, Papua New Guinea is the most linguistically diverse country in the world. To discover if the linguistic and cultural diversity was echoed in the genetic structure of the population, researchers studied the genomes of 381 Papuan New Guinean people from 85 different language groups within the country.

The researchers looked at more than a million genetic positions in the genome of each individual, and compared them to investigate genetic similarities and differences. They found that groups of people speaking different languages were surprisingly genetically distinct from each other.

Woman of a Papuan tribe in traditional clothes and coloring in New Guinea Island 
[Credit: Byelikova Oksana/Shutterstock]

Anders Bergström, the first author on the paper from the Wellcome Trust Sanger Institute, said: "This is the first large-scale study of genetic diversity and population history in Papua New Guinea. Our study revealed that the genetic differences between groups of people there are generally very strong, often much stronger even than between major populations within all of Europe or all of East Asia."

Professor Stephen J. Oppenheimer, second author of the paper from the Wellcome Trust Centre for Human Genetics, University of Oxford, said: "We found a striking difference between the groups of people who live in the mountainous highlands and those in the lowlands, with genetic separation dating back 10,000-20,000 years between the two. This makes sense culturally, as the highland groups historically have kept to themselves, but such a strong genetic barrier between otherwise geographically close groups is still very unusual and fascinating."

Locations of people studied from Papua New Guinea. Each language group is represented by a circle; the area indicates
 the number of genotyped individuals, and the color indicates the top-level language phylum. The study found that 
people speaking different languages were strongly genetically distinct from each other 
[Credit: Science doi: 10.1126/science.aan3842]

Human evolution in Europe and Asia has been greatly influenced by the development of agriculture around 10,000 years ago. When small bands of hunter-gatherers settled into villages and started farming, they expanded and over time gave rise to more genetically homogenous (similar) societies. However, despite the independent development of agriculture in Papua New Guinea at about the same time, the same process of homogenization did not occur here. This may indicate that other historical processes in Europe and Asia, such as the later Bronze and Iron Ages, were the key events that shaped the current genetic structure of those populations.

Dr Chris Tyler-Smith, corresponding author on the paper from the Wellcome Trust Sanger Institute, said: "Using genetics, we were able to see that people on the island of New Guinea evolved independently from rest of the world for much of the last 50,000 years. This study allows us to glimpse a different version of human evolution from that in Europe and Asia, one in which there was agriculture but no later Bronze Age or Iron Age. Papua New Guinea might show the genetic, cultural and linguistic diversity that many settled human societies would have had before these technological transformations."

Source: Wellcome Trust Sanger Institute [September 14, 2017]

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New study contradicts assumption that true frogs diversified as they expanded their range around globe

Evolutionary biologists long have supposed that when species colonize new geographic regions they often develop new traits and adaptations to deal with their fresh surroundings. They branch from their ancestors and multiply in numbers of species.

Ranidae family are most diverse frog group in the world, found on all the world's continents except Antarctica 
[Credit: Chan Kin Onn]

Apparently, this isn't the story of "true frogs." The frog family scientists call Ranidae are found nearly everywhere in the world, and their family includes familiar amphibians like the American Bullfrog and the European common frog.

New research from the University of Kansas appearing in Royal Society Biology Letters shows, in contrast to expectations, "the rapid global range expansion of true frogs was not associated with increased net-diversification."

"First, we had to identify where these true frogs came from and when they started their dispersal all over the world," said lead author Chan Kin Onn, a doctoral student at KU's Biodiversity Institute. "We found a distinct pattern. The origin of these frogs was Indochina -- on the map today, it's most of mainland Asia, including Thailand, Vietnam, Cambodia and Burma. True frogs dispersed throughout every continent except Antarctica from there. That's not a new idea. But we found that a lot of this dispersal happened during a short period of time -- it was during the late Eocene, about 40 million years ago. That hadn't really been identified, until now."

Next, Chan and co-author Rafe Brown, curator-in-charge of the KU Biodiversity Institute's Herpetology Division, looked to see if this rapid dispersal of true frogs worldwide triggered a matching eruption of speciation.

To establish the actual timing of true frogs' diversification, Chan and Brown performed phylogenetic analysis of 402 genetic 
samples obtained from an online database called GenBank. These samples represented 292 of the known 380 true 
frog species in the world [Credit: Rafe Brown]

"That was our expectation," Chan said. "We thought they'd take off into all this new habitat and resources, with no competition -- and boom, you'd have a lot of new species. But we found the exact opposite was true. In most of the groups, nothing happened. There was no increase in speciation. In one of the groups, diversification significantly slowed down. That was the reverse of what was expected."

To establish the actual timing of true frogs' diversification, Chan and Brown performed phylogenetic analysis of 402 genetic samples obtained from an online database called GenBank. These samples represented 292 of the known 380 true frog species in the world.

"We mined all of these sequences and combined them into a giant analysis of the whole family," Chain said. "It is to my knowledge the most comprehensive Ranidae phylogenetic analysis ever performed that included most of the representative species from the family."

Chan and Brown focused on four genes that would help to establish the family tree of true frogs.

"It's a genealogical pedigree of specimens, a family tree of species," Chan said. "Normally, you think of family tree as everyone in one family and how the various people are related. But this is more expanded where we look at how species are related to each other, so you can trace ancestry back in time."

The researchers concluded true frogs didn't become one of the most biodiverse frog family due to dispersing 
into new ranges, or due to filling a gap created by a catastrophic die-off. Rather, the rich diversity of species 
in the Ranidae family comes from millions of years' worth of continual evolution influenced by 
a host of different environs [Credit: University of Kansas]

After completing the phylogenetic analysis, the KU researchers used several frog fossils to "time calibrate" the history of the frogs' global dispersal.

"We use fossil frogs because we can accurately date the fossils," Chan said. "We know we found the fossil in a certain rock deposit, and we know with confidence how old the deposit is, so then we can estimate the age of the fossil."

After Chan and Brown deduced similarities between fossilized true frogs as reported by paleontologists and contemporary true frogs, they placed fossils into groups of closely related species, which scientists call genera.

"Using data from paleontological studies, we can loosely place a fossil where in the phylogeny it belongs and can put a time stamp on that point," Chan said. "That's where calibration happens, each fossil is sort of like an anchor point. You can imagine with a really big phylogeny, the more anchor points or calibration points the better your time estimate."

Through this process, the KU researchers concluded true frogs didn't become one of the most biodiverse frog families due to dispersing into new ranges, or due to filling a gap created by a catastrophic die-off (such as the Eocene-Oligocene Extinction Event that triggered widespread extinctions from marine invertebrates to mammals in Asia and Europe).

Rather, the rich diversity of species in the Ranidae family comes from millions of years' worth of continual evolution influenced by a host of different environs.

"Our conclusion is kind of anticlimactic, but it's cool because it goes against expectations," Chan said. "We show the reason for species richness was just a really steady accumulation of species through time -- there wasn't a big event that caused this family to diversify like crazy."

Source: University of Kansas [September 13, 2017]

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Scientists create alternate evolutionary histories in a test tube

Scientists at the University of Chicago studied a massive set of genetic variants of an ancient protein, discovering a myriad of other ways that evolution could have turned out, and revealing a central role for chance in evolutionary history.

University of Chicago graduate student Tyler Starr holds a vial of yeast cells engineered with a library of proteins 
comprising millions of possible evolutionary paths from our ancient ancestor to its modern function 
[Credit: Matt Wood, University of Chicago]

The study, published this week in Nature by UChicago graduate student Tyler Starr and Prof. Joseph Thornton, is the first to subject reconstructed ancestral proteins to deep mutational scanning—a state-of-the-art technique for characterizing massive libraries of protein variants. The authors’ strategy allowed them to compare the path that evolution actually took in the deep past to the millions of alternative routes that could have been taken, but were not.

Starting with a resurrected version of an ancient protein that evolved a new function some 500 million years ago—a function critical to human biology today—the researchers synthesized a massive library of genetic variants and used deep mutational scanning to analyze their functions. They found more than 800 different ways that the protein could have evolved to carry out the new function as well, or better than, the one that evolved historically.

The researchers showed that chance mutations early in the protein’s history played a key role in determining which ones could occur later. As a result, the specific outcome of evolution depended critically on the way a serial chain of chance events unfolded.

“By comparing what happened in history to all the other paths that could have produced the same result, we saw how idiosyncratic evolution is,” said Tyler Starr, a graduate student in biochemistry and molecular biology, who performed the paper’s experiments. “People often assume that everything in biology is perfectly adapted for its function. We found that what evolved was just one possibility out of many that were just as good, or even better, functionally than what we happened to end up with today.”

Molecular time travel

Over the last 15 years, Thornton, senior author on the new study and a professor in ecology and evolution and human genetics, led research that pioneered “molecular time travel” using ancestral protein reconstruction. In 2013, his team resurrected and analyzed the functions of the ancestors of a family of proteins called steroid hormone receptors, which mediate the effects of hormones like testosterone and estrogen on sexual reproduction, development, physiology and cancer. The body’s various receptors recognize different hormones and, in turn, activate the expression of different target genes, which they accomplish by binding specifically to DNA sequences called response elements near those targets.

Thornton’s group inferred the genetic sequences of ancient receptor proteins by statistically working their way back down the tree of life from a database of hundreds of present-day receptor sequences. They synthesized genes corresponding to these ancient proteins, expressed them in the lab and measured their functions.

They found that the ancestor of the family behaved like an estrogen receptor—recognizing only estrogens and binding to estrogen response elements—but during one specific interval of history, they evolved into a descendant group capable of recognizing other steroid hormones and binding to a new class of response elements. The researchers found that three key mutations before the emergence of vertebrate animals caused the ancestral receptor to evolve its ability to bind to the new target sequences.

That work set the stage for the current study. Knowing precisely how evolution played out in the past, Thornton’s group asked: Was this the only evolutionary path to evolving the new function? Was it the most effective one, or the easiest to achieve? Or was it simply one of many possibilities?

Alternate histories

Starr began working on the project during his first year as a graduate student, developing the technique to assess massive numbers of variants of the ancestral receptor for their ability to bind the new response element. First, he engineered strains of yeast in which the ancestral or new response elements drive expression of a fluorescent reporter gene. He then synthesized a library of ancestral proteins containing all possible combinations of amino acids at the four key sites in the receptor that recognize DNA—160,000 in all, comprising all possible evolutionary paths that this critical part of the protein could have followed—and introduced this library into the engineered yeast. He sorted hundreds of millions of yeast cells by their fluorescence using a laser-driven device, and then used high-throughput sequencing to associate each receptor variant with its ability to carry out the ancestral function and the new function.

Most of the variants failed to function at all, and some maintained the ancestral function. But Starr found 828 new versions of the protein that could carry out the new function as well, or better than, the one that evolved during history. Remarkably, evolution could have accessed many of these even more easily than the historical “solution,” but it happened not to, apparently wandering around the space of possible mutations until it arrived at the version of the protein in our bodies today.

“We all share the same gene sequence for this protein, so it might seem like evolutionary destiny, as if we’ve arrived at the best possible version. But there are hundreds of other directions that evolution could just as well have taken,” Thornton said. “There’s nothing special about the history that happened, except that a few chance steps brought us to this singular chance outcome.”

Thornton said that deep mutational scanning will be a powerful tool for evolutionary biologists, geneticists and biochemists, and he looks forward to using the approach on successive ancestors at different points in history to see how the set of possible outcomes changed through time.

“We have a molecular time machine to go back to the past, and once we’re there, we can simultaneously follow every alternate history that could possibly have played out,” Thornton said. “It’s a molecular version of every evolutionary biologist’s dream.”

Author: Matt Wood | Source: University of Chicago Medical Center [September 13, 2017]

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Back from the dead: how to revive a lost species

Scientists from around the world are hoping to return a lost species of giant tortoise to one of the world-famous Galápagos islands.

In 2008 the researchers found tortoises with the distinctive saddleback shells such as the adult tortoise, right, 
on Isabela Island in the Galápagos [Credit: Luciano Beheregaray, Flinders University]

The discovery of DNA links or ‘high ancestry’ to extinct Floreana species of giant tortoise means the mega-herbivore could one day be returned to the island for repatriation via a captive-breeding program – perhaps within the next five years.

Professor Luciano Beheregaray, Head of the Molecular Ecology Group at Flinders University, says the conservation effort will be a major milestone in jump-starting the recovery of the Foreana Island’s exotic ecosystem which critically depends on the mega herbivore.

The exciting discovery, outlined in Scientific Reports, describes how the discovery was made after an international expedition to a remote volcano on Isabela Island in the Galápagos found many giant tortoises with high ancestry from the extinct Floreana Island tortoise (Chelonoidis elephantopus).

Giant tortoises were transported by helicopter and then ship from the volcano’s slopes to the Galápagos National Park Breeding Center on the central island of Santa Cruz.

DNA analyses used by the experts from the US, Belgium, Ecuador, Greece, Italy and Australia, then assigned the ancestry of the relocated tortoises using reference databases containing data from all extant and extinct species of Galápagos giant tortoises.

The 23 relocated tortoises found to have high ancestry to the extinct Floreana species are now being used in a genetically-informed captive breeding program that aims to repatriate this species to Floreana Island.

“Our discovery and the captive breeding program raises the possibility that the extinct Floreana species could be revived,” says  ARC Future Fellow Professor Beheregaray, from Flinders University’s College of Science and Engineering (Biological Sciences).

Charles Darwin wrote about the harvesting of the species of tortoise found only on Floreana Island, which was exterminated within 15 years of his visit to the Galápagos in 1835.

Tortoises were removed from Floreana more than two centuries ago by mariners looking for food.

However, in 2008 the researchers found tortoises with the distinctive saddleback shells on Isabela, an island where native species have dome-shaped shells (see photo).

Several DNA-based analyses were then used to show that these animals were descendants of the Floreana species.

The latest study’s coordinator Adalgisa Caccone, from Yale University, says it was ironical that the haphazard translocations by mariners killing tortoises for food some 200 years ago has now created the unique opportunity to revive this lost species today.

As a result of that discovery, the Galápagos National Park, together with the Galápagos Conservancy, carried out an ambitious, logistically complex, and strenuous expedition in late 2015 to find and relocate genetic relatives of the extinct species of tortoise and to launch a breeding program aimed at restoring them to their native island.

“That expedition was a success,” says Professor Beheregaray.

Species are being lost at an unprecedented rate due to human-driven environmental changes. The cases in which species declared extinct can be revived are rare.

The geneticists are now working together with the Galápagos National Park and the Galápagos Conservancy to implement a monitored breeding program with the animals relocated from Isabela Island.

This program will strive to preserve in future generations the diversity of the breeders and to maximise the Floreana species’ genomic representation in their offspring.

The current plan is to release young tortoises on the island within five years.

Source: Flinders University [September 13, 2017]

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Explosion in number of known life forms

A remarkable effort from University of Queensland researchers has helped increase the number of known genomes by almost 10 per cent.

A total of 7280 bacterial and 623 archaeal genomes were obtained [Credit: iStock]

UQ School of Chemistry and Molecular Biosciences ARC Future Fellow Professor Gene Tyson said researchers obtained 7280 bacterial and 623 archaeal genomes (genetic materials from microorganisms) from environmental samples.

That represents an almost 10 per cent increase on the 80,000 genomes currently in genome repositories.

"The real value of these genomes is that many are evolutionarily distinct from previously recovered genomes," said Professor Tyson, Deputy Director of the Australian Centre for Ecogenomics (ACE).

"They increase the evolutionary diversity spanned by both bacterial and archaeal genome trees by over 30 per cent, and are the first representatives within 17 bacterial and three archaeal phyla."

Professor Tyson said much microbial diversity remained to be discovered, with the majority of microbes seen under the microscope not being amendable to being grown under laboratory conditions.

"Less than one per cent can be cultured, due to challenging factors including slow growth rates, fastidious growth requirements, and the need to cross-feed off other species," he said.

However, recent advances in sequencing technology and computational techniques allowed microbial genomes to be recovered directly from environmental samples, bypassing the need for laboratory cultivation.

"The approximately 8000 genomes recovered move us closer to a comprehensive genomic representation of the microbial world, but also show that much remains to be discovered," he said.

ACE co-researcher Dr Donovan Parks said for the first time, science had the required tools to make substantial inroads into the vast diversity of phylogenetic and metabolic life.

"We anticipate that processing of environmental samples deposited in other public repositories will add tens of thousands of additional microbial genomes to the tree of life," he said.

"Numerous studies have been reported during the completion of this research which have dozens or hundreds of evolutionarily diverse genomes from varying environments.

"The tools for obtaining genomes from environmental samples are continually improving and we expect that reprocessing the samples considered in this study will result in the recovery of additional genomes."

"Constructing a comprehensive genomic repository of microbial diversity lays the foundation for furthering our understanding of the role of microorganisms in critical biogeochemical and industrial processes."

The study was published in Nature Microbiology.

Source: University of Queensland [September 12, 2017]

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When ancient fossil DNA isn't available, ancient glycans may help trace human evolution

Ancient DNA recovered from fossils is a valuable tool to study evolution and anthropology. Yet ancient fossil DNA from earlier geological ages has not been found yet in any part of Africa, where it's destroyed by extreme heat and humidity. In a potential first step at overcoming this hurdle, researchers at University of California San Diego School of Medicine and Turkana Basin Institute in Kenya have discovered a new kind of glycan -- a type of sugar chain -- that survives even in a 4 million-year-old animal fossil from Kenya, under conditions where ancient DNA does not.

Partial upper jaw of Australopithecus anamensis, a primitive hominin, recovered from the bone bed 
excavated at the Allia Bay site [Credit: Meave Leakey, PhD]

While ancient fossils from hominins (human ancestors and extinct relatives) are not yet available for glycan analysis, this proof-of-concept study, published in Proceedings of the National Academy of Sciences, may set the stage for unprecedented explorations of human origins and diet.

"In recent decades, many new hominin fossils were discovered and considered to be the ancestors of humans," said Ajit Varki, MD, Distinguished Professor of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine. "But it's not possible that all gave rise to modern humans -- it's more likely that there were many human-like species over time, only one from which we descended. This new type of glycan we found may give us a better way to investigate which lineage is ours, as well as answer many other questions about our evolution, and our propensity to consume red meat."

Glycans are complex sugar chains on the surfaces of all cells. They mediate interaction between cells and the environment, and often serve as docking sites for pathogens. For millions of years, the common ancestors of humans and other apes shared a particular glycan known as Neu5Gc. Then, for reasons possibly linked to a malarial parasite that exploited Neu5Gc as a means to establish infection, a mutation that probably occurred between 2 and 3 million years ago inactivated the human gene encoding the enzyme that makes the molecule. The loss of Neu5Gc amounted to a radical molecular makeover of human ancestral cell surfaces and might have created a fertility barrier that expedited the divergence of the lineage leading to humans.

Today, chimpanzees and most other mammals still produce Neu5Gc. In contrast, only trace amounts can be detected in human blood and tissue -- not because we make Neu5Gc, but, according to a previous study by Varki's team, because we accumulate the glycan when eating Neu5Gc rich red meat. Humans mount an immune response to this non-native Neu5Gc, possibly aggravating diseases such as cancer.

In their latest study, Varki and team found that, as part of its natural breakdown, a signature part of Neu5Gc is also incorporated into chondroitin sulfate (CS), an abundant component in bone. They detected this newly discovered molecule, called Gc-CS, in a variety of mammalian samples, including easily detectable amounts in chimpanzee bones and mouse tissues.

Like Neu5Gc, they found that human cells and serum have only trace amounts of Gc-CS -- again, likely from red meat consumption. The researchers backed up that assumption with the finding that mice engineered to lack Neu5Gc and Gc-Cs (similar to humans) had detectable Gc-CS only when fed Neu5Gc-containing chow.

Excavation of the bone bed at the Allia Bay site, East Turkana, in 1996. A cross section of the bone bed 
can be seen passing diagonally from the center of the image to the right hand corner. This is the site 
where researchers collected a 4-million-year-old bovid fossil that contained Gc-CS 
[Credit: Meave Leakey, PhD]

Curious to see how stable and long-lasting Gc-CS might be, Varki bought a relatively inexpensive 50,000-year-old cave bear fossil at a public fossil show and took it back to the lab. Despite its age, the fossil indeed contained Gc-CS.

That's when Varki turned to a long-time collaborator -- paleoanthropologist and famed fossil hunter Meave Leakey, PhD, of Turkana Basin Institute of Kenya and Stony Brook University. Knowing that researchers need to make a very strong case before they are given precious ancient hominin fossil samples, even for DNA analysis, Leakey recommended that the researchers first prove their method by detecting Gc-CS in even older animal fossils. To that end, with the permission of the National Museums of Kenya, she gave them a fragment of a 4-million-year-old fossil from a buffalo-like animal recovered in the excavation of a bone bed at Allia Bay, in the Turkana Basin of northern Kenya. Hominin fossils were also recovered from the same horizon in this bone bed.

Varki and team were still able to recover Gc-CS in these much older fossils. If they eventually find Gc-Cs in ancient hominin fossils as well, the researchers say it could open up all kinds of interesting possibilities.

"Once we've refined our technique to the point that we need smaller sample amounts and are able to obtain ancient hominin fossils from Africa, we may eventually be able to classify them into two groups -- those that have Gc-CS and those that do not. Those that lack the molecule would mostly likely belong to the lineage that led to modern humans," said Varki, who is also adjunct professor at the Salk Institute for Biological Studies and co-director of the UC San Diego/Salk Center for Academic Research and Training in Anthropogeny (CARTA).

In a parallel line of inquiry, Varki hopes Gc-CS detection will also reveal the point in evolution when humans began consuming large amounts of red meat.

"It's possible we'll one day find three groups of hominin fossils -- those with Gc-CS before the human lineage branched off, those without Gc-CS in our direct lineage, and then more recent fossils in which trace amounts of Gc-CS began to reappear when our ancestors began eating red meat," Varki said. "Or maybe our ancestors lost Gc-CS more gradually, or only after we began eating red meat. It will be interesting to see, and we can begin asking these questions now that we know we can reliably find Gc-CS in ancient fossils in Africa."

Leakey is also hopeful about the role Gc-CS could play in the future, as an alternative to current approaches.

"Because DNA rapidly degrades in the tropics, genetic studies are not possible in fossils of human ancestors older than only a few thousand years," she said. "Therefore such ancient glycan studies have the potential to provide a new and important method for the investigation of human origins."

Author: Heather Buschman | Source: University of California - San Diego [September 11, 2017]

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A woman warrior from the Viking army in Birka

War was not an activity exclusive to males in the Viking world. A new study conducted by researchers at Stockholm and Uppsala Universities shows that women could be found in the higher ranks at the battlefield.

Illustration by Evald Hansen based on the original plan of the grave by excavator Hjalmar Stolpe, 
published in 1889 [Credit: Uppsala University]

Charlotte Hedenstierna-Jonson, who led the study, explains: "What we have studied was not a Valkyrie from the sagas but a real life military leader, that happens to be a woman".

The study was conducted on one of the most iconic graves from the Viking Age. It holds the remains of a warrior surrounded by weapons, including a sword, armour-piercing arrows, and two horses. There were also a full set of gaming pieces and a gaming board. "The gaming set indicates that she was an officer", says Charlotte, "someone who worked with tactics and strategy and could lead troops in battle". The warrior was buried in the Viking town of Birka during the mid-10th century. Isotope analyses confirm an itinerant life style, well in tune with the martial society that dominated 8th to 10th century northern Europe.

Anna Kjellstrom, who also participated in the study, has taken an interest in the burial previously. "The morphology of some skeletal traits strongly suggests that she was a woman, but this has been the type specimen for a Viking warrior for over a century why we needed to confirm the sex in any way we could."

The drawing is a reconstruction of how the grave with the woman originally may have looked. 
The illustration is made by Þórhallur Þráinsson [Credit: © Neil Price]

And this is why the archaeologists turned to genetics, to retrieve a molecular sex identification based on X and Y chromosomes. Such analyses can be quite useful according to Maja Krezwinska: "Using ancient DNA for sex identification is useful when working with children for example, but can also help to resolve controversial cases such as this one". Maja was thus able to confirm the morphological sex identification with the presence of X chromosomes but the lack of a Y chromosome.

Jan Stora, who holds the senior position on this study, reflects over the history of the material: "This burial was excavated in the 1880ies and has served as a model of a professional Viking warrior ever since. Especially, the grave-goods cemented an interpretation for over a century". It was just assumed she was a man through all these years. "The utilization of new techniques, methods, but also renewed critical perspectives, again, shows the research potential and scientific value of our museum collections".

The findings are published in American Journal of Physical Anthropology.

Source: Stockholm University [September 08, 2017]

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Why it's difficult to predict evolutionary fate of a new trait

The phrase "survival of the fittest" makes the principle of evolution by natural selection easy to understand—individuals with a trait that adapts them well to their circumstances are more likely to pass that trait along. But as a new study explains, multiple factors make predicting the fate of a trait fiendishly difficult.

The fitness of a genetic trait (an allele) may vary over time, rather than remain constant. In this simple model, 
populations with two different alleles (black or yellow) see-saw between advantage and disadvantage 
as their relative fitness changes over time (blue line below) [Credit: Weinreich et. al.]

Not only would improved predictive models help scientists better model how evolution works, but also they could aid in efforts to prevent infectious diseases. Every year, for example, vaccine makers, epidemiologists and physicians strive to predict where diseases such as influenza, Zika, HIV and Ebola may be headed next.

Fundamentally, the problem is that a trait conveyed by a gene variant, or allele, may be advantageous for one or a few generations, but provide no advantage or become a liability when circumstances change, said senior author Daniel Weinreich, a professor of ecology and evolutionary biology at Brown University. But most theoretical models of population genetics assume that fitness remains constant.

"We are articulating a number of different biological contexts in which the fitness of an allele might change over its 'lifetime' or lineage" in a population," Weinreich said. "We are convinced that the other contexts, where it is constant, are the exceptions, not the rule."

The new study in the Annual Review of Ecology, Evolution and Systematics provides an overview of what complicates predictive models and how scientists are trying to make progress, for the benefit of public health, among other areas.

"Infectious diseases experience constantly varying selective pressures as they spread within and between hosts and encounter drugs and host immune responses," said lead author Christopher Graves, who earned his Ph.D. from Brown and is now a researcher at Bayer. "Understanding how evolution proceeds in scenarios of highly variable selective pressures will increase our ability to predict drug resistance and disease outbreaks and ultimately lead to the creation and deployment of more clever drug and vaccine strategies."

Fitness can be fickle

Perhaps the most obvious way that the fitness of a trait can vary is that the environment can change, not only over time but also over space. Consider the population of a species of weed in a vacant lot. Some might carry an allele that helps them thrive in a hot sun and others might have an allele that conveys a relative advantage in cool shade. Not only could weather patterns change dramatically over timescales ranging from days to years, but also new buildings might go up or get torn down around the lot, creating new patches of shade or sun. A model projecting the fate of each allele becomes much more complicated along multiple dimensions.

Another dimension that can vary is the "social" life of alleles. Alleles that result in "cheating" are abundant in nature, but they are most effective when they are rare. Once everyone is cheating, it might no longer be an advantage, so the trait over time can become a victim of its own success. Moreover, genetic predispositions to cooperation doesn't just roll over. The paper cites cases in which "policing" behaviors have evolved, such as insects that preserve the supremacy of the queen by destroying the "selfishly" laid eggs of mere workers, or genes that produce a tumor-suppressing immune capacity to destroy cancer cells because they are growing too fast.

Conditions can even vary within a lineage because one allele might emerge that affects another. Weinreich has studied this in the emergence of antibiotic resistance in bacteria. He found that four mutations of a particular enzyme sometimes increased drug resistance and sometimes didn't, depending on what other mutations were present or absent.

Even more complications

That any of these circumstances can change over time adds yet another layer of complexity, Weinreich said, because the rate at which circumstances change matters. When circumstances change faster than the organism's rate of reproduction—for instance sunny or cloudy weather patterns that come and go over a few days—the sun- or shade-loving weeds each experience only minor influences on their reproductive success. But if circumstances vary more slowly—for instance a large new building shades the entire lot for decades—the sunny allele carriers could vanish from the lot and the shady allele will fully displace the other type. In this case, the sun-loving weeds may have gone extinct by the time the building is torn down again.

Indeed, Weinreich said, many models for predicting the fate of alleles have overlooked the possibility that traits can go completely extinct.

Meanwhile, the rate of environmental change is very similar to the rate at which natural selection acts, the math becomes especially tricky.

Pressing for progress

In their search for solutions, population geneticists have employed new approaches, Weinreich and Graves wrote. Among the most exciting, Weinreich said, are those in which they join forces with and borrow techniques from ecology and epidemiology—two fields in which modeling dynamic and complex change is central. This summer, for example, has featured a workshop, "Eco-Evolutionary Dynamics in Nature and the Lab" at the University of California at Santa Barbara's Kavli Institute for Theoretical Physics, that is dedicated to exploring such intersections.

Weinreich said he plans to delve deeper into the complexities of changes in fitness deriving from varying rates of change in social (e.g. cheaters), genetic (e.g. competing alleles) or environmental (e.g., weather) parameters.

"The overlap between ecological and evolutionary processes—that those two things speak to each other very intimately in a way that's been overlooked in many models—is the way forward," Weinreich said. "That's what's needed to make critical improvements to models."

Author: David Orenstein | Source: Brown University [September 08, 2017]

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