Genetics And Evolution Lecture 4

Front 1

1) The nobel prize in physiology or medicine, 2004? Who won, and what did they do and discover?

2) What are psuedogenes?

Back 1

1) Richard Axel and Linda Buck published a fundamental paper in 1991,describing this very large family of genes for odour receptors.

This represents about 3% of our total number of genes - all in thesame gene family.

There are 906 gene sequences that code for olfactory receptors inthe human genome that could bind to an estimated 10,000 odourmolecules.

Every single olfactory receptor cell expresses one and only one geneof all the genes that code for olfactory receptor molecules.

Homologues of these genes have been found in yeast and other fungi(where the may also recognise odour molecules), but the genefamilies in vertebrates are much bigger.

80% of human olfactorygenes appear in clusters

2) Pseudogene - an inactivated & non-functional copy of agene

Front 2

1) Three pathways of acquisition of new genes by duplication events?

Back 2

1) If genes with very similar functions are located next to each-other in the genome sequence then this suggests gene duplication. Gene duplication means that we can rapidly build up genes over evolutionary time and develop clusters.

-A gene duplicates and there can be a selective pressure on both of the genes, if this happens then the genes stay similar.

- If there is only a selective pressure on one of the genes then either one copy degrades (may become a psuedogene)- or- one copy acquires a new function- this leads to gene families.

Front 3

1) What are homologous genes? Orthologous genes? Paralogous genes?

Back 3

1) Homologous genes - genes that share a commonevolutionary ancestor

Orthologous genes - homologous genes located in thegenomes of different organisms

Paralogous genes - two or more homologous geneslocated in the same genome

Front 4

1) Why is gene duplication important? Evolution of the globin gene superfamily in humans? In mammalian Beta-globin? Human alpha and beta- globin gene clusters?

Back 4

1) Ancestral globin 800 Mya. 5 groups in the super family: Neuroglobin, Cytoglobin, and Myoglobin (the more ancient genes, are on separate chromosomes), the alpha-globins have 3 genes and are all on chromosome 16, and Beta-globins have 5 genes and are all on chromosome 11.

Evolution of mammalian Beta-globin genes involved many duplications, inactivations, fusions, conversions etc. There was a triplication of the genes in goats. Different evolutionary outcomes occur in different species. Evolution in some gene families might appear dynamic.

Human alpha- and beta- globin gene clusters, this gene family is small compared to the same family in other mammals. Both gene clusters contain genes expressed at differentdevelopmental stages (and contain at least one pseudogene).

Front 5

1) How does gene duplication occur?

2) What happens after a gene has been duplicated?

Back 5

1) Unequal crossing-over- so one cell receives two copies of one gene, one from the other non-sister chromatid.

Unequal sister chromatid exchange, an extra gene acquired by the other sister chromatid on the same chromosome.

2) Once there is more than one copy of a gene - sequence changescan occur in the extra copies. Each structural domain within a protein is an individual unit in apolypeptide chain & is coded for in continuous series of nucleotides. Additional genes can be created by domain duplicationduplication of segments within a gene.

Front 6

1) Domain shuffling?

Back 6

1) Domain shuffling is a phenomenon where the gene segments coding for functional domains are shuffled between different genes during evolution. The boundaries between different domains may or may not correspond to the intron-exon boundaries of the encoding gene. In fact, in certain cases a single domain is encoded by more than one exon, whereas an exon contains a number of functional domains.

Front 7

1) Domain shuffling in TPA?

Back 7

1) Domain shuffling in the tissue plasminogen activator (TPA). TPA is required for the breakdown of blood clots response in vertebrates(it is also used in clinical medicine to treat strokes).

The most likely explanation is that domain shuffling hasoccurred in the tissue plasminogen activator (TPA) gene, buthow this happened exactly is unclear.

Domain shuffling has lead to the evolution of a moresophisticated mechanism for breakdown blood clots inhumans. TPA has 4 exons & 4 structual domains: A finger module from fibronectin (binds fibrin in clots to activate TPA), A growth factor domain (stimulates cell proliferation), two kringle structures (binds to fibrin clots).

This indicates that there may be an advantage to shufflingdomains in this way.

Further research is required to identify a mechanism

Front 8

1) Whole duplications?

2) Examples? How did Saccharomyces evolve to become a good brewer?

Back 8

1) Generate extra copies of every gene (but no new genes). Increases the potential for new genes. Sequence of extra genes can begin to change withoutwithout modifying the function of the original gene.

Is there any evidence for this?Yes - Large, duplicated sets of genes in the same orderhave been identified in many organisms (recombinationevents may have moved some of the genes to newpositions over time).

2) Humans can induce whole gene duplications in crops.

Many sets of duplicated genes have beenfound in S. cerevisiae, ~800 gene pair,s376 gene pairs occur in 55 duplicated sets(set = at least 3 genes in the same order). Where did these extra genes come from?

Kluyveromcyces lactis shares a common ancestor with S. cerevisiae that lived100 million years ago (MYa). K. lactis and S. cerevisiae do not have the same gene pairsThis is because 10% of S. cerevisiae genes are likely to be derived from awhole genome duplication event (about 100 MYa).

In S. cerevisiae a whole genome duplication event occurred prior tothe duplication of the ADH gene. The extra copies of the ADH gene allows new functions of the ADHenzyme to evolve. In S. cerevisiae ADH catalyses the conversion of acetaldehyde toethanol. This enables S. cerevisiae to accumulate ethanol. This means S. cerevisiae can be used in fermentation and brewing.

Saccharomyces can survive for longer as can continue to exist for longer as can use ethanol as substrate.