Population genomics: Description, history, research applications, mathematical models, future developments

1. Population genomics is the large scale comparison of DNA
sequences of populations.
• Population genomics studies genome wide effects to
improve our understanding of microevolution so that we
may learn the phylogenetic history and demography of
a population.
Dr. Shiny C Thomas, Department of Biosciences, ADBU

2. History
• Population genomics has been of interest to scientists
since Darwin.
• Some of the first methods used for studying genetic
variability at multiple loci included gel electrophoresis
and restriction enzyme mapping.
• Advancements in sequencing and computer storage and
power have allowed for the study of hundreds of
thousands of loci from populations.

3. Research Applications
• In the study of S. pombe (more commonly known as
fission yeast), a popular model organism, population
genomics has been used to understand the reason for
the phenotypic variation within a species.
• However, since the genetic variation within this species
was previously poorly understood due to technological
restrictions, population genomics allows us to learn
about the species' genetic differences.

4. In the human population,
• population genomics has been used to study the genetic
change since humans began to migrate away from Africa
approximately 50,000 -100,000 years ago.
• It has been shown that not only were genes related to
fertility and reproduction highly selected for, but also
that the further humans moved away from Africa, the
greater the presence of lactase.

5. A 2007 study done by Begun et al.
• compared the whole genome sequence of multiple lines of
Drosophila simulans to the assembly of D. melanogaster
and D. yakuba.
• This was done by aligning DNA from whole genome
shotgun sequences of D. simulans to a standard reference
sequence before carrying out whole genome analysis of
polymorphism and divergence.
• This revealed a large number of proteins that had
experienced directional selection.
• They discovered previously unknown, large scale
fluctuations in both polymorphism and divergence along
chromosome arms.

6. • They found that the X chromosome had faster divergence
and significantly less polymorphism than previously
expected.
• They also found regions of the genome (e.g. UTRs) that
signalled adaptive evolution.

7. In 2014 Jacquot et al.
• studied the diversification and epidemiology of endemic
bacterial pathogens by using the Borrelia burgdorferi
species complex (the bacteria responsible for Lyme
disease) as a model.
• They also wished to compare the genetic structure
between B. burgdorferi and the closely related species B.
garinii and B. afzelii.
• They began by sequencing samples from a culture and
then mapping the raw read onto reference sequences.

8. • SNP based and phylogenetic analyses were used on both
intraspecific and interspecific levels.
• When looking at the degree of genetic isolation, they
found that intraspecific recombination rate was ~50
times higher than the interspecific rate.

9. Moore et al conducted a study in 2014
• in which a group of Atlantic Salmon populations which
were previously analyzed with traditional population
genetic analyses (microsatellites, SNP array genotyping,
BAYESCAN) to place them into defined conservational
units.
• This genomic assessment mostly agreed with previous
results, but did identify more differences between
regionally and genetically discrete groups, suggesting
there were potentially even greater number of
conservation units of salmon in those regions.

10. • These results verified the usefulness of genome wide
analysis in order to improve the accuracy of future
designation of conservation units.
Mathematical Models
Understanding and analyzing the vast data that comes from
population genomics studies requires various
mathematical models.
• One method of analyzing this vast data is through QTL
mapping.
• QTL mapping has been used to help find the genes that
are responsible for adaptive phenotypes.

11. • To quantify the genetic diversity within a population a
value known as the fixation index, or FST is used.
• When used with Tajima's D, FST has been used to show
how selection acts upon a population.
• The McDonald Kreitman test (or MK test) is also
favored when looking for selection because it is not as
sensitive to changes in a species' demography that would
throw off other selection tests

12. Future Developments
Most developments within population genomics have to do
with increases in the sequencing technology.
For example,
• restriction site associated DNA sequencing, or RADSeq is
a relatively new technology that sequences at a lower
complexity and delivers higher resolution at a
reasonable cost.
• Highthroughput sequencing technologies are also a
rapidly growing field that allows for more information to
be gathered on genomic divergence during speciation.

13. • Highthroughput sequencing is also very useful for SNP
detection, which plays a key role in personalized
medicine.
• Another relatively new approach is reduced
representation library (RRL) sequencing which discovers
and genotypes SNPs and also doesn't require reference
genomes.
Ref: Personal genomics
Population groups in biomedicine