Clues to genetic origins of schizophrenia revealed

A recent study on the origin of schizophrenia, a neurodevelopmental disorder, was recently conducted. Due to the human genetic diversity, as well as the evolutionary and ancestral ties, the Xhosa population of South Africa was used in this study.  They analyzed over 1800 case studies and controls regarding the Xhosa population, with controls for age, gender, and residency. This study was conducted to better understand the origins of schizophrenia, a disorder where many individuals often do not have children. They used whole-exome sequencing on 1,826 individuals (i.e. cases and controls). Many of the genes are involved in organization and function of brain synapses, which is critical to memory.

Overall, when an individual has a severe mutation in an associated gene, it depends on the biology of the gene, mutation of gene function, and secondary events to determine whether the individual develops schizophrenia. The damaging mutation in the associated gene may not afflict the individual that it appears in first, but rather in later generations.


Kailie Batsche

Potluck for 3 March 2020

Link (paper and image): https://science-sciencemag-org.proxygw.wrlc.org/content/sci/367/6477/569.full.pdf

Authors: 

S. Gulsuner, D. J. Stein, E. S. Susser, G. Sibeko, A. Pretorius, T. Walsh, L. Majara,
M. M. Mndini, S. G. Mqulwana, O. A. Ntola, S. Casadei, L. L. Ngqengelele, V. Korchina,
C. van der Merwe, M. Malan, K. M. Fader, M. Feng, E. Willoughby, D. Muzny, A. Baldinger, H. F. Andrews, R. C. Gur, R. A. Gibbs, Z. Zingela, M. Nagdee, R. S. Ramesar, M.-C. King*, J. M. McClellan

Cdh1 and Brain Size -A. Williams 3/3/20 potluck

While looking for genetic causes of microcephaly, a study done by Rodriguez, Sanchez-Moran et al (2019) found a missense mutation p.Asp187Gly in Cdh1/Fzr1) that was determined to be the cause of the microcephaly in a 4 year old patient. The heterozygous mutation was de novo and the authors state that it is "intriguing" that such a simple change had such drastic effects. Experiments on mice showed that this missense mutation causes the loss of function in APC/C (anaphase-promoting complex/cyclosome) which causes impairment of neurogenesis leading to microcephaly. APC/C-Cdh1 is specifically involved in axon growth, synapses, and has been linked to functions involving learning and memory. This study claims that Cdh1 is now a strong candidate for being involved in the evolution of human cortical brain size and expanded intelligence, although this particular study never mentioned whether there were differences in the sequence between modern humans, extinct hominins with available genetic data, and other extant primates. 

-Alexis W. potluck 3/3/20

https://onlinelibrary-wiley-com.proxygw.wrlc.org/doi/full/10.1111/jnc.14835

Multiplex X/Y-PCR Improves SexIdentification in aDNA Analysis

By amplifying the amelogenin gene sex can be determined for individuals that scientists are able to extract aDNA from. This is done because the X-chromosome has markers which are DXS6789 and DXS9898 while males only show one allele. This is important because we can now use this to check for a sampling bias among the anthropologists themselves by checking their sex determination with this technique. This can also be used for children and stillbirths since they are too young to use morphological techniques to sex them.

Potluck post 2/25/2020
Annelise Beer

https://onlinelibrary.wiley.com/doi/full/10.1002/ajpa.10172

Potluck: Investigating mechanisms of brain development through Neanderthal DNA

• Alysson Muotri (UC San Diego) grows brain organoids, or miniature brain models, to study brain development. 
• Research by Philip Gunz (Max Planck Institute) has attempted to triangulate genes involved in the differential brain and skull development in Neanderthals compared to modern humans. One study identified present-day individuals whose cranium was the most 'Neanderthal-like' compared to others, with increased volume of the occipital and lower parietal regions, identified associated gene variants. Two genes stood out that had been characterized in mice, one involved in development of the putamen and another in myelination of the cerebellum. The overall amount of Neanderthal DNA also correlated positively with a more 'Neanderthal-like' skull shape.
• Muotri has now spliced these Neanderthal variants into brain organoids to create 'Neanderoids,' which have a different morphology compared to typical brain organoids. These organoids are capable of sending signals to small robots, enabling them to walk. 
• The researchers are hoping to uncover developmental differences as a result of these variance that may further elucidate cognitive, social and behavioral differences between humans and Neanderthals.

 Mackenzie Hepker, 2/25/2019

https://www.nature.com/articles/d41586-019-02210-6

aDNA Analysis Provides Insight into Origins of Pacific Dogs

Previous studies examining the origin of Australian dingoes and Pacific dogs suggest that they dispersed from a common ancestor from South China. In this study, Zhang et al. (2020) analyzed 7000 to 2000 year old mtDNA from dog remains from around the Yangtze and Yellow River basins. They found that their ancient samples belonged to the A1b haplogroup, which occurs at high frequencies in modern-day Australian dingo populations but is rare in Chinese dogs. Because the haplotype is rare in modern Chinese dog populations, the authors suggest a replacement of this haplogroup by the A1a haplogroup, which was not found in the ancient samples. The wide geographic range of a subhaplogroup, A1b2, also has implications for determining human dispersal. Analysis on this haplogroup suggests that humans (and dogs) from mainland China radiated to southeast Asia and Indonesia before reaching eastern Melanesian and Polynesian islands.

Audrey Tjahjadi 

Link to original article: https://academic.oup.com/mbe/advance-article-abstract/doi/10.1093/molbev/msz311/5698279?redirectedFrom=fulltext

Genome Sequence of a 5,310-Year-Old Maize Cob Provides Insights into the Early Stages of Maize Domestication

Something I've always found interesting is how studies on ancient DNA can help complement things we have learned from the archaeological record. Archaeological studies have suggested maize was domesticated around 10,000 to 6,250 years ago in southern Mexico.

In this paper, researchers sequenced the DNA from a 5,310-year-old cob of maize, and discovered it was genetically more similar to modern varieties of domesticated maize than its wild counterpart. This suggests domestication had already progressed substantially. However, there are a number of differences from modern maize, showing that domestication was a gradual process which continued to shape domesticated maize over the millennia.

The map shows distribution of two wild ancestors of domesticated maize, and the Tehuacan Valley, where the maize sample was found.


https://www.sciencedirect.com/science/article/pii/S0960982216311204

Zac Truesdell, potluck, 2/25/2020

SOX2 Gene and Cancer Research

Manjusha Vaidya and Kiminobu Sugaya published a paper in PLOS ONE on Feb 24th that describes a gene that they have linked to cancers such as breast cancer. SOX2 is a gene that is highly expressed in cancer stem cells and can be used to understand cancer formation, progression, and metastasis. They hypothesized that these embryonic stem cell gene expressions made CSCs more resistant to conventional chemo and radiation therapies. But the occurrence of a cancer susceptibility related SOX2-SNP in genomic, cytoplasmic as well as exosomal DNA might be valuable as a general cancer susceptibility marker that is not specifically limited to cancers of breast or gallbladder. Thus the SOX2 gene is an indispensable player in cancer progression and malignancy grade determination giving it great value in patient survival.

Journal Post 2/24/2020
Annelise Beer

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229309

Reconstructing Denisovan Anatomy Using DNA Methylation Maps

In 2019 an Israel-based team sought to tackle the boundary between morphology and molecules using one of the most enigmatic human ancestors: Denisovans. Paradoxically known better from their DNA than from their fossils, this team wanted to see what would happen if they tried to work backwards and reconstruct a hypothetical Denisovan body using deferentially methylated regions of the genome that are linked to specific phenotypic traits. The team tested this method on chimpanzees and Neanderthals with ~85% accuracy, and project what they think a Denisovan would look like. Their results present a Denisovan skull broadly similar to the Neanderthal hypodigm with subtle differences illustrated above, such as a broader cranium, longer tooth row, and more robust jaw than Neanderthals.

Ryan McRae
Potluck 2/25/20
https://www.cell.com/cell/pdf/S0092-8674(19)30954-7.pdf

Emergence of human-adapted Salmonella enterica is linked to the Neolithization process

Emergence of human-adapted Salmonella enterica is linked to the Neolithization process 

Authors: Key et al. 2020 (led by Felix M. Key, Alexander Herbig, and Johannes Krause of the Max Planck Institute for the Science of Human History)

Recently, aDNA analysis identified human-specific bacterial pathogen Salmonella enterica in two skeletons (450 and 800-yr-old), prompting an in-depth genomic study of the pathogen. 

Using human teeth from Eurasian Neolithic until the Middle Age, researchers analyzed 2,739 ancient metagenomes using DNA extracted from the dental pulp chamber (~6,500-yr-old). 

They found eight ancient Salmonella genomes, found within the AESB and contained the human-adapted serovar Paratyphi C. During the transition from a nomadic lifestyle to that of farming, roughly ~10,000ka, humans lived in close proximity to domestic animals and their waste. During this time human-adapted pathogens, like Salmonella enterica were able to emerge, allowing for the evolution of the S. enterica pathogen to occur over thousands of years, linking it to human culture. 

One of the ways that we are able to study ancient pathogens is through skeletal indicators and fossil evidence. With pathogens like Salmonella, there are no skeletal lesions or physical indicator for archaeologists to find. By using recent advances in ancient DNA, researchers are now able to conduct paleogenomic studies on clinically relevant pathogens and study human diseases in a new light. 

Kailie Batsche

Potluck for 25 February 2020

Citation: Key, F.M., Posth, C., Esquivel-Gomez, L.R. et al. Emergence of human-adapted Salmonella enterica is linked to the Neolithization process. Nat Ecol Evol (2020). https://doi-org.proxygw.wrlc.org/10.1038/s41559-020-1106-9

Link to article: https://www-nature-com.proxygw.wrlc.org/articles/s41559-020-1106-9

Image: https://www.sciencemag.org/news/2020/02/farming-gave-us-salmonella-ancient-dna-suggests

Using aDNA to track archaic STI’s!

The Role of aDNA in Understanding

the Coevolutionary Patterns of Human Sexually Transmitted Infections

Clinical and historical pathogen genomes have been sequenced to perform phylogenetic analyses on sexually transmitted infections to better understand the coevolutionary relationships between host and pathogen. In this paper, HPV and human ectoparasites were specifically examined. The use of environmental DNA coupled with ancient DNA was considered due to the low amounts of diverse ancient DNA material available. Ancient DNA has changed our view of human evolution and we should continue to study the coevolution of hominins and pathogens. 

https://www.ncbi.nlm.nih.gov/m/pubmed/29941858/

Kristin Carline potluck contribution 2/24/20

Neanderthal-Denisovan ancestors interbred with a distantly related hominin

X, Y, N, D, and S label Africa, Europe, Neanderthal,
Denisovan, and superarchaic pop.

In the past few years since the Denisovan reference genome was published, numerous studies have been conducted on their relationship to modern humans and Neanderthals. Rogers et al., 2020 presents evidence of interbreeding between the ancestors of Neanderthals and Denisovans, who interbred with an older Eurasian “superarchaic” population. This population is thought to have separated from other humans over 2 million years ago and could have been as large as 20 to 50 thousand individuals. Rogers et al. argue that the Neanderthal and archaic population had separated over 1.2 million years prior to the interbreeding event. They also suggest that there were two divided subpopulations within the larger archaic population, who each independently interbred with either 1) Neanderthals or 2) Denisovans.

Joshua Porter - 02/24/2020 Potluck

https://advances.sciencemag.org/content/6/8/eaay5483.abstract

Ancient DNA puts a face on the mysterious Denisovans, extinct cousins of Neanderthals

Today, the only Homo species walking on earth is us, Homo sapiens. In comparison, the late pleistocene could be imagined as the world of Homo where several hominin species were living at the same time. The one that sparks the most curiosity would most certainly be the Denisovans. Known only through genetic data and a few fossil fragments, how Denisovans look like remains mainly a mystery. However, many scientists are still itching to find out the morphology of this mysterious human species. 

Ancient DNA might be able to help ease this itch until more fossil evidence is discovered. Using a method based on epigenetics, researchers were able to compose the face of a Denisovans girl. In the process of DNA methylation, cytosine degrades overtime and researchers were successful in creating a methylation "map" using ancient DNA. They then compared the signals they retrieved from this map with modern human phenotype data and created the composite in the picture above. 

This research sheds new lights to the morphology of the cold-adapted Denisovans. However, as we know that even early Homo sapiens had various morphs, it is important to remember that phenotypic data derived from individual DNA might not be representative to the entire species. 

Ancient DNA puts a face on the mysterious Denisovans, extinct cousins of Neanderthals

https://www.sciencemag.org/news/2019/09/ancient-dna-puts-face-mysterious-denisovans-extinct-cousins-neanderthals

Monica Cheung– Feb 24th, 2020

Potluck: Identifying and Interpreting Apparent Neanderthal Ancestry in African Individuals

As we all know, prior to the introduction of this study, admixture was only thought to be found in non-African ancestry with at least 2% of derived Neanderthal genes found in European populations while Oceanic populations having an additional 2%-4% of ancestry attributed to the Denisovans. Previous approaches, such as S*(Plagnol and Wall, 2006; Vernot and Akey, 2014), CRF (Sankar-araman et al., 2014), diCal-admix (Steinru ̈cken et al., 2018),and HMM (Skov et al., 2018), used an ‘‘unadmixed’’ modern reference panel of an African population as a c control for false positives resulting in masking the Neanderthal introgressed sequence in African populations. How this study differs is that the contributors applied a method called IBDmix (Identity by descent) to exclude the African reference panel used in prior studies from collected genotypes from Eurasia, African and American populations using only an Archaic reference genome to then calculate the amount of probability at a variant site in modern individuals. 

Results show that samples from North African populations show an average of 17Mb of Neanderthal sequence and 1.2Mb Denisovan sequences in African individuals. With significant overlap of Neanderthal identified sequencing Africans populations show a sharing of more than 94% of the Neanderthal sequence between non-African populations. Two demographic models were tested to determine if a signal could be detected by an IBDmix, i.e. Neanderthal sequence via hybridity, migrating back to Africa or an early pre out of Africa dispersal. Yields show that both pre-OOA human-to-Neanderthal gene flow and elevated historic back migration contribute to the signal of Neanderthal ancestry detected in Africans.

Overall, 38 non-Africa-specific-high-freguency-haplotypes and 13 African- specific high frequency haplotypes were recorded. The 13 African-specific high-frequency Neanderthal haplotypes we identified show enrichment for genes involved in immunological function (e.g., IL22RA1 and IFNLR1) and ultraviolet-radiation sensitivity (e.g., DDB1 and IL22RA1)

Article

Warrenkevin Henderson

Ancient DNA reveals twenty million years of aquatic life in beavers

This study used ancient mitochondrial DNA from the extinct giant beaver, Castoroides ohioensis, to determine the phylogenetic relationship between extinct beavers and the two extant species of beaver. They also wanted to determine if the aquatic lifestyle and unique ability to alter their environment in beavers originated with their common ancestor or evolved independently. The results suggest giant beavers are a sister taxa with both extant beaver species. Additionally, because both the giant beaver and extant species exhibited behaviors such as woodcutting and environmental engineering, as well as their aquatic lifestyle, the authors conclude the most parsimonious explanation is that these behaviors originated with their common ancestor, approximately 20 million years ago. This date also correlates with the disappearance of terrestrial beavers from the fossil record.

Rachel Nelson, 3/3/19 Potluck
https://www.researchgate.net/profile/Axel_Barlow/publication/339018423_Ancient_DNA_reveals_twenty_million_years_of_aquatic_life_in_beavers/links/5e394caaa6fdccd96584aaf0/Ancient-DNA-reveals-twenty-million-years-of-aquatic-life-in-beavers.pdf

Ancient DNA of the Extinct Jamaican Monkey Xenothrix Reveals Extreme Insular Change within a Morphologically Conservative Radiation

The four endemic platyrrhine species of the Caribbean have been long extinct but questions remain about their phylogenetic relationships to one another and extant primate species. The authors of Ancient DNA of the Extinct Jamaican Monkey Xenothrix Reveals Extreme Insular Change within a Morphologically Conservative Radiation extracted aDNA from the Jamaican monkey Xenothrix mcgregori to help resolve these questions. They found that this species belongs to the Callicebinae (titi monkey) clade and diverged from its sister taxa, Cheracebus, approximately 11ma. Interestingly, Xenothrix mcgregori has a suite of derived traits but Callicebinae is known for being a morphologically conserved group. Furthermore, the authors found that there were at least two primate colonization events in the Caribbean.

Time-Calibrated Phylogeny of Several Platyrrhine Genera including Xenothrix

Link to Paper: https://www.pnas.org/content/115/50/12769

Elaine Miller – Potluck 2/25/2020

Neanderthal diet and disease inferred from ancient DNA in dental calculus - A. Williams potluck 2/25/20

After analyzing the shotgun-sequencing from the dental calculus of five Neanderthals from Spy, Belgium and El Sidron, Spain, the authors claim that populations of Neanderthals had vastly different diets that varied depending on their environment. Contrary to what was previously thought, only the Spy samples returned strong evidence of Neanderthals consuming large portions of meat. The El Sidron samples only contained sequences of plants and mushrooms. 

Incredibly, one of the Neanderthal calculus samples returned the oldest commensal draft microbial genome sequenced to date at 48,000 years and was given its own subspecies designation: Methanobrevibacter oralis neandertalensis. The authors claim that the Neanderthal with both a dental abscess and evidence of living with a pathogen that causes acute diarrhea showed evidence of self-medication by consuming large amounts of poplar, which contains salicyclic acid (active ingredient in Aspirin) and sequences from Penicillium.   

https://www.nature.com/articles/nature21674

Using ancient DNA to look at biodiversity and human behaviour

This article from PNAS gives an interesting application of ancient DNA sequencing, but looking at the biodiversity of animals bones at historic settlement in New Zealand. The authors can begin to understand the animals that were inhabiting New Zealand at the time as well, which animals were being hunted and if transportation of animals bones meat and products was occurring. The use of Ancient DNA here is an ideal way to get more human behavioural data, whilst simultaneously validating and improving the information we get from the fossil record.


Link to paper: https://www.pnas.org/content/115/30/7771.short

Jack Richardson

Molecular Anthropology and Race

This paper briefly discusses the history and the racist agenda of some scientists in the past that tried to find differences in races by a blood test. Even used this biased data to go so far as to say that on the human evolutionary tree Europeans are distinct from the Afro-Asian branch. This launched other scientists to search for the truth about their race in relation to their molecular data using mtDNA. This research has found that there is more variation in the African samples than other populations. They bring up a good point near the end because scientists are trying to find the origin of species and a dispersal pattern. While people widely accept that animals such as rats originate in the same place and disperse from there but the same is not widely accepted for humans. But now we have all this molecular data that points to our African origin and how we are related but people still see people as separate "races" even though it is a cultural construct. 

(I felt that this paper was a really good summary of the papers we read this week)

https://nyaspubs.onlinelibrary.wiley.com/doi/full/10.1111/j.1749-6632.2000.tb05580.x

Potluck Post 2/18/2020

Annelise Beer 

Humans and chimps more genetically similar than mice and rats

While reading a review on the genomic comparisons of brain evolution (get ready!), one line jumped out at me from the introduction:

"Genetically, humans are close to other apes: the genetic distance between humans and chimpanzees or bonobos is on the order of 1–5% (depending on the types of genetic divergence considered) and reflects the recent divergence of the species. By comparison, the difference between the common mouse and rat species, Mus musculus and Rattus norvegicus, respectively, ranges from 20% to 50%."

- M. Somel, X. Liu and P. Khaitovich (from 'Human brain evolution: transcripts, metabolites and their regulators,' Nature Reviews Neuroscience, 2004).

The authors indicate that the common mouse and rat have a ~10x greater genetic difference between their genomes than do humans and chimpanzees/bonobos. While I'm not an expert on mice or rats (or chimpanzees or humans), intuitively, humans vs. chimpanzees/bonobos exhibit more significant differences in terms of morphology, ecology and behavior than do mice vs. rats.

What, then, do the greater differences between mice vs. rats compared to humans vs. chimpanzees indicate about the evolutionary context of the mouse/rat divergence?  Compared to other rodents, rats have many rat-specific segments of repeats; the mouse genome has a particular deletion of a gene possessed by other rodents, including rats. When similar ecological niches are ultimately occupied and behavioral/functional repertoires expressed by the two species, are these genetic differences evidence of a bottleneck or founder effect in a common ancestral population? Are the similarities given such genetic differences evidence of convergent evolution between the two lineages? How can these be teased apart?

Further reading:
Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC, Burch PE, Okwuonu G. Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature. 2004 Apr 1;428(6982):493.
https://www.nature.com/articles/nature02426

Cooper GM, Brudno M, Stone EA, Dubchak I, Batzoglou S, Sidow A. Characterization of evolutionary rates and constraints in three mammalian genomes. Genome research. 2004 Apr 1;14(4):539-48.
https://genome.cshlp.org/content/14/4/539.full

Mackenzie Hepker