Gene Duplication

Paralogs

* copies that coalesce at a duplication event

Duplication event

* type of mutation in which one or more copies of a DNA segment is produced
* arises from %%unequal crossing over%% during %%meiosis%% between %%misaligned homologous chromosomes%%

Orthologs

* coalesce at a ^^speciation^^ event

Another diagram of speciation and duplication events

* first duplication occurs
* ^^speciation^^ event into A and B
* red and blue in each species

when duplication occurs assume…

* assume through multiple generations that the single duplication event which would have occurred in a single individual gets PASSED on and now everybody in that entire population has that duplication event
* and now everyone in the population has 2 copies 2 loci

during speciation event…

* lineage gets split into two different groups (A and B) (represented by tubes)

since everyone got both copies from duplication event …

* both of these species lineages (A and B) will inherit both copies (blue and red)

same colors are…

* orthologs

different colors are…

* paralogs

Draw diagram with


1. duplication event
2. speciation event for both copies (2)
3. duplication event for one of the copies
4. 2 speciation event

Real world example of speciation and duplication event like the graph represented:

* split in ancestral globin gene
* in some species (a vertebrate) there was duplication and one of them became primitive for of %%HEMOGLOBIN%% and the other %%MYOGLOBIN%% (550 million years ago)
* Another duplication event occurs in hemoglobin
* @@B-hemoglobin@@
* @@a-hemoglobin@@
* we need both types to produce the oxygen carrying molecules in blood

disentangle the diagram

* name each line
* m(A), m(C), m(B) → myoglobin in species A, B, and C
* h(A)
* α(C), α(B)
* β(C), β(B)
* remove the species (tubes)
* move all colors away from each other (still attached to the tree)

Duplication tree for ancestral myoglobin like molecule

Getting rid of speciation events from original disentangled diagram

* only keep one branch per color
* doesn’t matter which branches are removed

Why do we get rid of speciation events?

* strip away the noise
* tens of thousands of vertebrate species since first globins evolved
* looking only at duplication

Hagfish example

* lineage that ==never== had a ==duplication event== in the hemoglobin
* no alpha or beta hemoglobin
* red line only

jawed fish and land vertebrates have …

distinct alpha and beta globin genes

Why did B-globin gene go through additional duplication events

* evolution of %%fetal hemoglobins%% in mammals
* fetal hemoglobin: makes the hemoglobin in fetus have a %%greater affinity for oxygen%%
* fetus gets %%97-98%%% of oxygen
* %%selective advantage%%: grows faster (and possibly larger)

Expression of human hemoglobin genes as a function of developmental age

* alpha hemoglobin gets developed early on when the fetus starts to develop the circulatory system and gets express all throughout life
* %%gamma%% is main fetal hemoglobin
* while fetus is gestating and the embryo is gestating it produces gamma version of the beta hemoglobin
* gamma has HIGHER affinity for oxygen
* Once baby is born there is a ^^switch^^
* ==stops== expressing ==gamma== type of beta hemoglobin
* %%starts%% expressing regular %%beta%% hemoglobin

Why does there have to be a switch from gamma type beta hemoglobin to beta hemoglobin being expressed after being born

\*switching works exactly the same way in males and females

* when females became pregnant, if they still use gamma there ==won’t be any advantage== for fetus having a higher affinity for oxygen

HOW does gamma type beta being expressed switch to beta hemoglobin being expressed

change in transcription factors

* shuts down transcription of gamma type of beta hemoglobin
* up-regulates the transcription of regular beta hemoglobin

Partial pressure (O2) and percent Hb saturation graph

pseudogenes

Pseudogenes are **nonfunctional segments** of DNA that ***resemble functional*** genes.

if an organisms has a gene, the gene has been retained because

it has some positive function value

Why is the most efficient way for new functions to evolve through gene duplication and NOT pleiotropy

* Pleiotropy: a single gene having multiple functions by influencing more than one trait
* evolution of new functions still highly constrained, as it allows new function to work well, it degrades original function

Exon shuffling

* once there are two or more copies recombination can occur (exon shuffling)
* thus, you can start making combinations amongst the one different duplicated genes
* further allows you to potentially produce new function

what happens to one locus after gene duplication

1. turns into pseudogene
2. Both copies retain OG function
3. one copy evolves new function


1. neofunctionalization
4. the copies optimize different original, pleiotropic functions


1. subfunctionalization

probability of new function is actually…

quite low

* lose function, because mutation is not a directed process

How could both copies retain original function after going through gene duplication

* especially when a lot of gene product is needed
* you need a LOT of ribosomes to make all those different proteins collectively
* if selection favors OG functions

Ribosomal RNA genes are a case of

lots and lots of DNA duplication

Repeated gene duplication can lead to

gene clusters on the same chromosome

what can produce gene families

* chromosomal breakage and re-anealing

what ARE gene families

gene clusters occurring on two or more chromosomes

Some important gene families

* hemoglobin family \~10 genes
* Olfactory receptor family (\~900 genes; over 60% pseudogenes in humans)
* Immunoglobulin family (\~800 genes)

How did cells evolve to create chemical mechanisms to protect themselves as O2 levels increased

* prokaryotic globin binds and “detoxifies” oxygen present in cell’s environment

globin gene duplication and divergence diagram