Lecture 16 Evolution of human genome

Question 1

Human population. When do we start counting?

Answer 1

About 117 billions modern humans have existed
-Currently 8 billion people, 7% of the total who have ever live

Question 2

What makes us human?

Answer 2

*Changes in the skeleton and mode of locomotion
*Increase brain size
*Smaller, fewer and less specialized teeth
*Stereoscopic vision
*Grasping hand with opposable thumb

*Physiology
*Behaviour
*Naked skin
*Parental care

*Opposable thumb
*Brain
*Social nature
*Language

Our genome

Question 3

What is a Genome?

Answer 3

*An organism’s complete set of DNA, including all its genes
*Contains all the info to build and maintain an organism
*It includes both genes and non-coding sequences of DNA/RNA

“Genomeistheentirecollectionofgenesandallother functional and non-functional DNA sequences in an organism in a haploid set of chromosomes”

Question 4

Structural genes:

Answer 4

DNA segments that code for
some specific RNAs or proteins.(mRNAs, tRNAs, snRNAs, scRNAs)

Question 5

Functional sequences

Answer 5

Regulatory sequences:occur as regulatory elements (initiation,promoter,operatorsites,etc.)

Question 6

Non-Functional sequences

Answer 6

Introns and repetitive sequences. Needed for coding, regulation and replication of DNA. Much higher than functional sequences

Question 7

Human Genome Project

Answer 7

International scientific project to identify and map all the genes from both a physical and a functional standpoint

thought in 1984launched in 1990 *complete on April 2003 (3b USD)

Sequenced only euchromatic regions (92.1% of the genome). Heterochromatic regions -centromeres and telomeres-were not sequenced

Question 8

Whole genome sequencing How much does it cost?

Answer 8

based on moor’s Law it has exponentially decreased as technology has improved

• it originally cost $100 million and currently costs a couple 100 dollars

Question 9

New technologies for sequencing

Answer 9

High-throughput sequencing technologies:
*Pyrosequencing
*Illumina dye sequencing
*SMRT sequencing

They all used the shotgun technique approach(via genome fragmentation

Question 10

Human genome

Answer 10

Nuclear DNA -23 pairs chromosomes

*Small mitochondrial DNA

3 billion bp- 24,000 genes

17,000 bp-38 genes

Human genome has 3.2 billions bpGenes differ in size
*Dystrophin gene has 2.4 Mbp
*Chromosome 1 has 3168 genes (biggest)

*Chromosome Y has 344 (smallest)
*Chromosome 2 has something weird.. We expected to have more than 100,000 genes…..We have 24,000

Gene are scattered, separated by non-coding DNA.This DNA was called “junk DNA”- About HALF of our genome is non-coding !

“Junk DNA” plays an important role:
*Providing evolutionary material to work on
*Controlling the genes’ activity
*Long non-coding RNA, MicroRNA
*Acting as switches for genes in the body

Question 11

Comparative genomics

Answer 11

Once realised the importance of genomic, scientists started to look into other organism

Question 12

How many genomes do we have?

Answer 12

How many genomes do we have?Earth BioGenomeProjectstarted in November 2018, aiming to sequence all genomes of known eukaryotic species (1.5M)in 10 years

Question 13

HapMap Project

Answer 13

Goal to compare genetic sequences of different individuals➔Genetic variants -single-nucleotide polymorphisms (SNPs)

We can then find:
*Our genetic common denominator
*A better response to individual drug treatment

Question 14

How genes can affect us

Answer 14

They affect our chances of having:
*several common illnesses
*heart disease
*asthma and diabetes but so do many other factors, such as diet and lifestyle

Question 15

Benefit of Genomics

Answer 15

Precision medicine

*Causes, diagnosis and treatment of disease
*Early detection of rare diseases *Predicted tests
*Tests for common cancers and heart disease
*Developing targeted medicines

Examples-to treat specific types of cancer cells (HER2
-positive breast cancer cells)
-using tumour marker testing to help diagnose cancer

Other benefits
*Studying human evolution
*Comparing genomics
*Identification of mutations linked to cancer
*Design medication and more accurate prediction of their effects
*Forensic applied sciences

Question 16

Synthetic biology and bioengineering

Answer 16

*Seeks to create new biological parts
*Redesign systems that are already found in natural

Question 17

Animal Evolutionary Genomics

Answer 17

The evolution of animal genome helps us identify how:
*changes in genomes affected changes in phenotypes
*the evolutionary processes that led to genome change

Increase in complexity ≠ increase in genome size
We found that:
*Less diversity within animals in terms of gene number and other genome features than expected
*No correlations complexity-genome size!

Question 18

The C-paradox

Answer 18

The C-paradox
‘C-value’ is a way of measuring the amount of haploid DNA content per nucleus (1 picogram= 1 gigabase)

No correlation between complexity and genome size
*similar species can have quite different genome sizes
*genes and regulatory sequences evolve slowly and conservatively
*genome size can change rapidly on evolutionary timescales

Explanation can be found in the ‘non-functional’ DNA, but Natural selection wouldn’t tolerate junk…

Question 19

Selfish DNA elements

Answer 19

Mechanism that creates large amounts of junk DNA faster than natural selection deletes it.

It refers to those sequences of DNA which
1.Spread by forming additional copies of them self within the genome
2.Makes no specific contribution to the reproductive success of its host organism
3.Can be neutral and/or deleterious to the carrier organism

Question 20

Transposome

Answer 20

Transposomeelement Aluhas a million copies and accounts for about 10% of our genome.

*45% of our genome relics of TEs (80% in corn)
*Evidence of interspecies lateral gene transfer

Question 21

T haplotype allele in mice: genes can be selfish

Answer 21

T locus in mice affect tail length and viability in males

*TT = normal long tail

*tt= short tail, sterile ➔Damaging for individual, Natural Selection should get rid of it.

*Tt = short tail, 90% of sperm contain the t allele➔Disables sperm which doesn’t contain itself

Question 22

Mechanisms of genome evolution

Answer 22

Chromosomesets or parts

Accidents in meiosis can lead to one or more extra sets of chromosomes (polyploidy)

Duplications and inversions resultfrom mistakes during meiotic recombination

Chromosome can break, fuse, and so on.

Diploid parent (2n) -> polyploid offspring (4n)

Question 23

Alterations of Chromosome’s structure

Answer 23

Humans have 23 pairs of chromosomes

Chimpanzees have 24pairs

Following the divergence of humans and chimpanzees from a common ancestor, two ancestral chromosomes fused in the human line

*Origin, duplication, loss of genes
*Coding sequence: site insertion, deletion and substitution
*Modifications of regulatory regions
*Horizontal gene transfer
*Modification of local repeats (including satellite DNA, tandem repeats)

Question 24

Genotype and Phenotype

Answer 24

Not all changes in genomes result in changes in phenotypes!

*What is the phenotypic impact of particular genomic differences?
*What phenotypes are evolutionarily accessible?

Human and the gene ‘X’

Question 25

Are we still evolving?

Answer 25

For a species to have a new trait that affect the population:

*New mutation arise
*Spread into the population
*Change in allele frequencies

What has changed since 30,000 years ago?
-Larger and denser populations: contagious diseases rapidly spread
-Massive pandemics
-Marked change in diet: vegetarian and cereal grain-dependent, milk
-New adaptation to new environment
-Greater genetic diversity make adaptations more likel

Question 26

Specific recent adaptations

Answer 26

*Alleles that confer lactose tolerance
*High altitude adaptations (Tibet, Ethiopia, Andes)
*Metabolism of fat-rich diet (Inuit)

Micro-evolution: change in gene frequency -YES
Macro-evolution: formation of species -NO