13. Genomics in use Flashcards
Explain what is comparative genomics
Comparative genomics - compare the complete genome sequences of different species - identify unique genes -> infer functional roles
What are the current pojects which will be useful in comparative genomics?
Earth biogenome project - aims to sequence all life on Earth - will be able to compare many species:
- UK initiative - Darwin Tree of Life
- EU initiative - ERGA
Are all genes across human genome equally constraint?
No, some not conserved at all - ex brain size - other under a lot of constraint - measured by evolutionary conservation score phyloP - some human genes even lack evolutionary constraint
What is an example of human genome lacking evolutionary constraint?
Human accelerated regions (HAR) - excess mutations in humans - HARs located under human specific genes - ex: in the brain - cognitive abilities - HARs influence 3D organisation of proteins - enhances regulatory element binding - regulates human specific expression
What are HARs?
Human accelerated region (HAR) - sequences that changed little throughout mammalian evolution, but experienced a burst of changes in humans since divergence from chimpanzees
What is Anthropocene and why is it important?
Anthropocene - human-derived change - since 1950 new functionally and stratigraphically distinct geological epoch - black carbon, inorganic ash, fertilizers, pesticides, artificial radionuclides, increase in CO2, CH4, glibal temperature increase
Did rapid animal extinction begin in Anthropocene?
No, earlier - in holocene but after Homo Sapiens arrived in the Americas 14000 BCE - in XXist century 60% decline in populations - verall decrease in biodiversity
What are the reasons for major loss of biodiversity and population decrease on Earth?
Reasosn for decrease in biodiversity and populations:
- agricultural and urban development
- climate chnage
- poaching
How can genomics help with declining biodiversity and populations?
- Use ancient DNA to learn from what went extinct -
- Study current populations to see which populations need to eb prioritised
=> objective criteria for identification and analysis - identify species under threat - decide on conservation strategy
How can analysing ancient DNA help in conservation?
Can help establish genomic hallmarks of populations that are heading towards extinction - can compare:
- genetic diversity
- inbreeding levels
What are the two types of DNA samples used in sequencing?
- Modern DNA
- Ancient DNA - low quantity, low quality (fragmented), contaminated
What is the story of two mammoths?
Two mammoth aDNA sampels compared - one lived in larger earlier population (Oimyakon), the other in smaller dying isolated population (Wrangel) - comapred their genomes - genomic traces of uncoming extinction:
- lower genetic diversity
- higher inbreeding
What is an example of two populations which genomes can be compared to see the effects of conservation work
Gorillas - Grauer’s and Mountain gorillas experience critical population decline - but Mountain gorillas received conservation efforts (since 1970s?) but Grauer’s didn’t because die outside of their natural environments - compare past and current genomics - museum samples + field samples -> significant loss of genetic diversity in Grauer’s but stable in Mountain which were conserved by human efforts
What is the source of past genomic samples?
Museum animal spcecimens - scrape off DNA from skulls
What has to be considered in applying conservation work?
Need to objectively decide if conservation wrok needed - see genomics, populations + test after events which could influence
What genes experience high rates of mutations before species go extinct?
Increased mutation rates in essential genes - ex:
- immune response
- reproductive processes
Key points about genomics in conservation
Why we should sequence genomes of diverse organisms?
Explain what is metagenomics
Metagenomics - studies genetic material recovered directly from environmental / clinical samples by sequencing - contains genomes of many species
What are the environments where metagenomics can be studied?
Metagenomics studied environments:
- natural
- human-made
- host-associated
What are the benefits of studying metagenomics?
Study metagenomics to:
- understand how complex environments function
- discover new bioactive substances
- recognise changes in environment compositions to identify disease / seasonality / climate change / human-driven change
What are the main goals of metagenomic experiments?
Metagenomics aims to determine:
- what is in the sample - the species
- what are the functions - figure out functional profiles of enzymes, pathways
What is the workflow of a metagenomic experiment?
How is genome mapping performed in metagenomic experiments?
How is relative species abundance estimated in metagenomic experiments?
How is functionality inferred in metagenomic experiments?
What is the network of antimicrobial resistance spread?
Antimicrobial resistance (AMR) is not constraint only in pathogens that concern human health - anitbiotics enter the ecosystem - AMR emerges in random bacterial species => if want to effectively decrease AMR need to tackle all network - otherwise problem won’t be solved
What is the timeline of antibiotic discovery vs resistance emergence?
First antibiotic mass produced in 1950s - penicillin - resistant strains found very quickly - resistance spreads — Sweden introeduced anti-anitbiotic control measures early on because the more you use antibiotics, the higher the resistance
What is used as a past sample of microbial life for genomic analysis?
Microbial fossils - dental calculus - calcified bacterial biofilms - don’t change over time - dental calculus samples taken from musuem specimens -> metagenomic studies identify the bacterial communities of the past -> can screen AMR profiles
What is the workflow for metagenomics from dental calculus?
What was the experimental design to study emergence of AMR in the environment since introduction of antibiotics?
Chose to study Sweden - implemented antibiotic control measures in 80s - chose bear populations to look at dental plaques because they avoid human habitats as much as posssible - perfect for tracing AMR in distant environments - pre-antibiotic era samples for genomic comparison taken from museum bear teeth calculus specimen
Comparing bear teeth calculus metagenomics before and after Swedish control measures on the use of antibiotics
The measure was effective - after it was imposed the observed AMR load was lower -> everything is connected in the environment
