Presentation is loading. Please wait.

Presentation is loading. Please wait.

Molecular Evolution Sylvia Nagl. Relationships between DNA or amino acid sequence 3D structure protein functions Use of this knowledge for prediction.

Similar presentations


Presentation on theme: "Molecular Evolution Sylvia Nagl. Relationships between DNA or amino acid sequence 3D structure protein functions Use of this knowledge for prediction."— Presentation transcript:

1 Molecular Evolution Sylvia Nagl

2 Relationships between DNA or amino acid sequence 3D structure protein functions Use of this knowledge for prediction of function, molecular modelling, and design (e.g., new therapies) Sequence-structure-function paradigm CGCCAGCTGGACGGGCAC ACCATGAGGCTGCTGACC CTCCTGGGCCTTCTG… TDQAAFDTNIVTLTRFVM EQGRKARGTGEMTQLLNS LCTAVKAISTAVRKAGIA HLYGIAGSTNVTGDQVKK LDVLSNDLVINVLKSSFA TCVLVTEEDKNAIIVEPE KRGKYVVCFDPLDGSSNI DCLVSIGTIFGIYRKNST DEPSEKDALQPGRNLVAA GYALYGSATML

3 A novel sequence or structure Prediction based on “similarity” = evolutionary relatedness

4 Evolution as an algorithmic process Random mutation (genotype) “mutate” Selection (phenotype) “select” Differential reproduction “replicate” The term algorithm denotes a certain kind of formal process consisting of simple steps that are executed repetitively in a defined sequential order and will reliably produce a definite kind of result whenever the algorithm is run or ‘instantiated.’ ‘cumulative’

5 Cumulative selection will work on almost anything that can yield similar, but non-identical, copies of itself through some replication process. It depends on a medium that stores information and can be passed on to the next generation - DNA or RNA (virus) in terrestrial life forms. Most genetic mutations are deleterious - proofreading and error correction mechanisms - negative selection Whenever positive selection acts, it can be thought of as selecting DNA with particular phenotypic effects over others with different effects. Advantageous mutations may confer a survival and reproductive advantage on individuals who will then, on average, pass on more copies of their genetic material because they will tend to have a larger number of offspring. Over many generations, the accumulation of small changes can result in the evolution of DNA sequences with new associated phenotypic effects.

6 Genes and gene- related sequences 900Mb Extragenic DNA 2100Mb Single-copy genes Multi-gene families Regulatory sequences Non-coding tandem repeats DNA transposons LTR elements LINEs SINEs Satellite DNA Minisatellites Microsatellites Dispersed Tandemly repeated Coding DNA 90Mb Noncoding DNA 810Mb Pseudogenes Gene fragments Introns, leaders, trailers Unique and low-copy number 1680Mb Repetitive DNA 420Mb Genome- wide interspersed repeats Roadmap of the human genome

7 Multi-gene families: Evolution by gene duplication Gene duplication is the most important mechanism for generating new genes and new biochemical processes. This mechanism has facilitated the evolution of complex organisms: In the genomes of eukaryotes, internal duplications of gene segments have occurred frequently. Many complex genes might have evolved from small primordial genes through internal duplication and subsequent modification. Vertebrate genomes contain many gene families absent in invertebrates. Many gene duplications have occurred in the early evolution of animals (“Biology’s Big Bang”, “Cambrian explosion”, ~570-505 million year ago).

8

9 A duplication may involve a single gene (complete gene duplication) part of a gene (internal or partial gene duplication) part of a chromosome (partial polysomy) an entire chromosome (aneuploidy or polysomy) the whole genome (polyploidy) Types of duplication events

10 Unequal sister chromatid exchange at meiosis Unequal crossing-over at meiosis Gene duplication: Mechanisms

11 Transposition via an RNA intermediate RNAcDNA transcription reverse transcription reintegration DNA transposons transposon replication Gene duplication: Mechanisms

12 Homology: Paralogy, orthology and xenology a ab duplication speciation species 1species 2 abab paralogous orthologous ‘Redundant copy’

13 Random mutation (genotype) “mutate” Selection (phenotype) “select” Differential reproduction “replicate” Duplication – mutation in ‘redundant copy’ – paralogy - new function

14 Complete gene duplication pseudogene (silent) deleterious mutations invariant repeats “tandem arrays” increased gene product Examples: large quantities of specific rRNAs or tRNAs, histone proteins amplified esterase gene in Culex mosquito variant repeats sequence divergence HOX/HOM genes function or regulation may differ Dayhoff (1978): at least 50% identity: gene family >35% identity: homologous (super)family

15 Evolution of Hox and HOM gene clusters by gene duplication mouse Amphioxus Drosophila hypothetical ancestor gene duplication Antennapedia Bithorax

16 Duplicated gene segments often correspond to functional or structural domains. A domain is a well-defined region within a protein that either performs a specific function or constitutes a stable structural unit. Domain duplication is a form of internal duplication. This mechanism may increase number of active sites enable acquisition of a new function by modifying the redundant segment. Domain duplication increases the functional complexity of genes in evolution. Internal gene duplication: Domain duplication

17 Internal repeats in the apolipoprotein genes The structural and functional module: a 22-mer repeat In exon 4 of the genes belonging to this family, this 22-mer is repeated 1 to ~15 times. The presence of many copies lead to the evolution of new functions: apoE now plays a role in neural regeneration, immunoregulation, growth and differentiation, via interactions with low-density lipoprotein receptors and apoE receptors.

18 Gene evolution by domain shuffling 1. Internal duplication Duplication of one or more domains 2. Domain insertion Structural or functional domains are exchanged between proteins or inserted into a protein “Mosaic or chimeric proteins”

19 Examples: Two common domains Kringle domain from plasminogen protein EGF-like domain from coagulation factor X

20 Domain insertion: “Mosaic proteins” Structural modules: plasminogen kringle domain EGF domain fibronectin finger domain vit. K-dependent calcium- binding domain (osteocalcin) tissue plasminogen activator urokinase prothrombin plasminogen Domain origins: trypsin-like serine protease Mosaic proteins fibronectin epidermal growth factor (EGF)


Download ppt "Molecular Evolution Sylvia Nagl. Relationships between DNA or amino acid sequence 3D structure protein functions Use of this knowledge for prediction."

Similar presentations


Ads by Google