#molbio

Previously a study identified a list of domestication-associated genes in modern humans by comparing their genome with extinct human species. These genes overlapped with domesticated animals but not with their wild equals. This finding sheds light on the possibility of human domestication.

The self-domestication hypothesis suggests that during evolution, modern humans underwent a self-induced domestication process that anatomically resulted in a lighter built skeleton, a more juvenile look (smaller brow ridges, nasal projections, teeth, and cranial capacity), and a larger brain when compared to their earlier counterparts. In other words, this process encourages selection against aggression and preserves the “cuter” attributes.

One way of explaining the domestication process is the neural crest hypothesis of domestication, which proposes that domestication is attributable to alteration in migration and the mild deficiency of neural crest cells during embryonic development. Neural crest cells (NCC) are responsible for inducing and developing neuroendocrine cells, pigment cells, neurons and glial cells of the sensory, sympathetic and parasympathetic nervous systems, and many skeletal and connective tissue components of the head.

“Neurodevelopmental disease modeling for the study of human evolution” was the unique approach adopted by a recent study that dissects the role of BAZ1B in domestication as well as affirms the neural crest hypothesis.

The study considered a cognitive disorder, namely Williams syndrome (WS). WS shares many similarities with domestication-related modifications. The parallels between the two include decreased aggression, hypersociability, reduced head size, elfin face, pointy ears, small jaw and teeth, short stature, accelerated sexual maturity, etc. Hence, WS is synonymous with hyper-domesticated human phenotype. The syndrome is caused by hemideletion of 28 genes at the 7q11.23 region. BAZ1B (a chromatin regulator) gene plays a crucial role in NCC maintenance and movement; intriguingly, one copy of this gene is missing in individuals with WS.

To evaluate the contribution of BAZ1B in making us “cuter,” i.e., domestication/WS-related facial modifications, neural crest stem cell lines were cultured, and the gene activity was altered in each cell line. The paper concluded impairment in NCC migration and outgrowth upon a decrease in BAZ1B, proving the involvement of BAZ1B in NCC development in humans. Additionally, it was found that the reduced expression of the BAZ1B gene led to distinct facial features (similar to WS), establishing the gene as an essential driver of facial appearance. Thus this paper provided the first experimental evidence for the neural crest hypothesis as an explanation to domestication where BAZ1B is one of the genes driving this process. Furthermore, the knockdown of BAZ1B also affected EDN3, MAGOH, and ZEB2 expressions. These genes are associated with behavioral changes as a result of domestication.

Studies indicate that these genes are also involved in the development of cognitive processes like language or theory of mind. Thus further introspection can bring about a clear picture of the anatomical, behavioral, and physiological alterations resulting from self-domestication in humans.

Reference:

january study challenge—day 15

halfway—did you make any / have you kept up with your new years resolutions?

let’s see:

monthly

finish this study challenge!

doing well so far!

catch up in all my classes

caught up in one of them, need to do the other three but I do have a lot on my plate right now so I’m hoping to get to them asap

finish knitting the hat I started a month ago

haven’t had time to sit down and knit for a few hours yet. I’m hoping I’ll still be able to wear it once I finish 😅

reorganise my room to later have friends over for dinner

I’ve done the kitchen, bathroom, and my desk. need to tackle the main floor now but that’s going to take a While.

start a journal + get into a routine

this one hasn’t been as good yet, though I am going to try to sit down this weekend and write something or other

yearly

work on my physical fitness / be able to do 1 (one) push-up

got a few gym sessions with friends already in the works!

be more involved in my course’s Fachschaft

kicking booty with this one! we’ve got the fachschaftstag on saturday so I’ll be able to put more on my overfilling plate

journal once a week

working on it!

complete two internships that I hopefully find interesting!

currently talking to an advisor about organising something!

get back into sewing

currently have plans to go to the nearby city to check out sewing machines once this semester’s over

Gene drive can be explained as a phenomenon whereby a particular gene via genetic engineering methods biases inheritance in its favour (more than the Mendelian 50:50 inheritance chance) resulting in the gene becoming more prevalent in the population over successive generations. The speed of this process is inversely correlated to the generation time of the organism, eg: it is faster in mosquitoes with a generation time of 2-4 weeks than in whales with generation time of 50 years or more.

This idea is mostly being explored as a potentially durable and cost effective strategy for controlling the transmission of deadly vector-borne diseases that effect millions of people worldwide such as malaria, dengue, Zika virus, or to eliminate herbicide or pesticide resistance. Eg: The Cas9 mediated gene drive led by Gantz et. al. in the mosquito population by introgression of parasite-resistance genes, thereby modifying the ability of the vector to transmit the pathogen.

Though the dangers of this technology cannot be overlooked. One of the ideas was a suggestion to use CRISPR gene editing technology to avert extinction of endangered wildlife by spreading a fertility reducing gene in the other animals competing against them for resources. This with time turned from an innovative idea to a perilious one, as demonstrated in a CRISPR-Cas9 gene drive targetted at genes that control the differentiation of the two sexes of the Anopheles gambiae mosquitoes. Leaving the males unaffected it decreased the fertility of the female mosquitoes. The gene rapidly spread reaching 100% prevalence within 7-11 generation to the point of total population collapse despite various Cas9-resistant genes arising in each generation.

With just a few of these engineered organisms our ecosystem could be altered, irrevocably.

References: 1) Gantz, V. M., Jasinskiene, N., Tatarenkova, O., Fazekas, A., Macias, V. M., Bier, E., & James, A. A. (2015). Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi. Proceedings of the National Academy of Sciences, 112(49), E6736. https://doi.org/10.1073/pnas.1521077112

2) Kyrou, K., Hammond, A., Galizi, R. et al. A CRISPR–Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes. Nat Biotechnol 36, 1062–1066 (2018). https://doi.org/10.1038/nbt.4245

3) Emerson, C., James, S., Littler, K., & Randazzo, F. (Fil). (2017). Principles for gene drive research. Science, 358(6367), 1135. https://doi.org/10.1126/science.aap9026

It is a long standing dogma that genes which code for essential functions tend to be conserved over the course of evolution. In a recent study, this was contradicted with the fact that some new genes had swiftly become crucial because they regulated heterochromatin (which is one of the fastest evolving part of the DNA, therefore, the genes that regulate it have to adapt quickly to keep up).

The researchers focused on the Nicknack ZAD-ZNF gene, which is an evolutionarily young gene in Drosophila species. Nicknack encodes a heterochromatin-localizing protein.

To see how quickly Nicknack might have taken over an essential function, the researchers replaced the Nicknack gene in D. melanogaster with the Nicknack gene in its closest evolutionary relative, D. simulans. They expected that the swap of an essential gene would have no effect as it would be conserved and hence similar in both species. But they found that the divergent D. simulans Nicknack protein could only localize to D. melanogaster heterochromatin and rescue viability of female but not the male fruit fly.

Reason: The swap adversely affected the males, with their abundance of heterochromatin in the Y chromosome. Rendering the D. simulans Nicknack gene incapable of handling the load of large quantity of evolutionary diverse heterochromatin.

Conclusion: D. melanogaster had rapidly evolved it's own version of Nicknack gene (despite being an essential gene) to prevent it from becoming obsolete.

How does the 2 m DNA fit into a nucleus of 10-15 μm diameter? The answer lies in DNA packaging.

To better understand the chromatin compaction levels, read our new infodump!

Click on the link below!!

https://sites.google.com/view/bobthebiotechquer/molecular-biology/dna-packaging

https://sites.google.com/view/bobthebiotechquer/molecular-biology/dna-topology

DNA topology is an essential property of the cell and is regulated by Topoisomerases for its proper functioning.

To learn more about Topology and the enzymes, read our new infodump!

Click the link in our bio and go to 'Molecular Biology'.

Reference:

Ahmad, M., Xue, Y.,et.al. (2016). RNA topoisomerase is prevalent in all domains of life and associates with polyribosomes in animals. Nucleic acids research, 44(13), 6335–6349. https://doi.org/10.1093/nar/gkw508