1st half review Flashcards
how can genome size change during evolution of single genus
large variation within species– correlation between number of retrotransposons and gene size
How can genomes expand in size?
- amplification of transposons, especially retrotransposons
- polyploidy (recent)
- expansion of other non-coding regions
- large segmental duplications
how can genomes decrease in size?
- recombination that eliminate DNA
- between repeats or between transposons
- more deletions relative to insertions
Draw unequal crossing over BTW LTR retrotransposons
intra and inter element recombination
Effects of genome size
- variation in distance between genes and gene density
- due to TEs
- can vary in different regions of chromosomes
- can vary in species
cellular effects of genome size increases
- nucleus size
- cell size
- duration of cell cycle
- cell differentiation rate
class 2 TEs
DNA elements “cut and paste”
- transposition through DNA intermediate: element excises and reinserts elsewhere in genome
- autonomous or non-autonomous elements
- autonomous - code for transposase
- non-autonomous – don’t code for transposase
- terminal inverted repeats
Class 1 elements
RNA elements: retrotransposons - mRNA intermediate - usually high copy number A) LTR retrotransposons - long terminal repeats in direct orientation - gag and pol coding regions - gag= capside like, pol= RT, protease etc. --Nucleus, RT in cytoplasm, cDNA transport to nucleus B) non-LTR retrotransposons - most common in human genomes - no terminal repeats - LINEs - autonomous -SINEs - non-autonomous --nucleus, priming and RT at target site
Draw DNA, LTR, non-LTR transposons
DRAW
effects of TEs that insert into genes
- insertional mutagenesis
- insert into exon
- insert into enhancer
- insert into repressor - Epigenetic regulation
- antisense downregulation
- - inserts into 3’ region and makes antisense RNA to form dsRNA– rna degraded and downregulated
- epigenetic silencing
- - metalation of transposon to prevent proliferation - Introduction of new information
- TEs bring new enhancers/ repressors
- TEs introduce new splice sites
- TEs bring new promoter or start site - Transduction!
- introduce new exon into gene
- 5’, 3’, or premature polyadenylation
Nested retrotransposons
- transposons often insert into other transposons
- not selected against
- each retrotransposon originated later than DNA flanking it
- can lead to greatly increased distance between genes and to increased genome size
Dating of insertion retroelements
for non-nested
- LTR dating to infer timing
- LTRs same upon insertion, then diverge
- LTR divergence level indicates age of insertion
Families of TEs
- phylogenetic analysis of AUTONOMOUS based on ORFs within TEs
- shows relative TE relatedness
epigenetic silencing of retrotransposons and mechanisms
Transcriptional silencing - methylation of TE promoters - chromatin remodeling Post-transcriptional silencing - sequence specific RNA degradation - double stranded RNA, formed by readthrough transcription from neighboring gene -- inverse of antisense degradation - siRNAs can target TEs for degradation
paleopolyploidy
ancient polyploidy events, more than ~10 mya
- 2R in vertebrates
- multiple rounds during flowering plant evolution
paleopolyploidy in vertebrates
2 rounds, one before emergence of jawless fish, and one after
fish-specific genome duplication
paleopolyploidy
- many genes present in 2 copies in teleost fish but one copy in other vertebrates
- pairs in teleost seem to have originated at the same time
how is paleopolyploidy detected
- find duplicated blocks of genes
- estimate relative ages of blocks using synonymous substitutions (Ks)
- Analyze degree overlap between adjacent blocks;
- if overlap = segmental duplications not polyploidy
Polyploidy if: large duplicated, non-overlapping regions, with genes of similar ages
evolution after paleopolyploidy
- organism returns to diploid state by chromosomal structural changes, (rearrangements and fusions)
- many duplicated genes lost
- duplicated genes that are retained often diverge in expression patterns
- one copy may experience relaxation of purifying selection or occasionally positive selection
- retained duplicated undergo subcellular relocalization
- neo or sub functionalization can occur
evolutionary and ecological significance of polyploidy
- novel phenotypes
- speciation— mechanism of instant speciation
- ecological diversification
- often can colonize new habitats
- new alleles for gene evolution because all genes are duplicated
- major effects on genome evolution
polyploidy in plants
prominent and ongoing in plants
- many crop plants are polyploids
ex. canola, cotton, bread, strawberry
polyploidy in animals
not as common as in plants
- some polyploidy fish, amphibians and insects, but rare in mammals, NOT IN BIRDS
- ancient polyploidy in vertebrate evolution
mechanisms of polyploidy formation
-union of unreduced (2N) gametes: produces tetraploid
- union of one reduced and one unreduced gamete:
= triploid
– usually inviable, ex. seedless watermelon
- experimentally induced by colchicine treatment
– microtubule inhibitor that prevents cell division
polyploidy and gene evolution
- gene loss immediately and over time
- chromosomal rearrangements
- changes in DNA methylation and histone modifications
- neo and sub functionalization
gene expression changes in polyploidy
- up or down regulation of expression compared to parents
- silencing of one or both homeologs
- possible mechanisms include DNA methylation, histone modifications (methylation and deacetylation)
- can be organ specific or in response to stress conditions
types of gene duplications
tandem
segmental
chromosomal
whole genome
tandem duplicates
found in clusters of 2 or more members, usually 2-6/cluster
- sometimes clusters interrupted by non-related gene
- due to recombination effect
- 14-17% of genes in human genome
- (+) correlation with recombination rate
- usually formed by unequal crossing over
- if promoter gene not duplicated – altered gene regulation or pseudogene
- can undergo recombination– concerted evolution
mechanisms for gene duplication
unequal crossing over
retroposition
segmental duplications
1kb to over 200kb
- 5% of human genome, on all chromosomes
- duplicative transpositions of small portions of a chromosome
- common in pericentromeric and subtelomeric regions
- identified by computational methods and by fluorescent in situ hybridization
dispersed duplications
generated by retroposition or DNA transposition after gene formation
retroposed duplications
generated by retroposition
some have regulatory elements some become pseudogenes
fates of duplicated genes
- one copy lost or looses function/expression
- pseudogene - both copies retain original function
- can be redundant - one copy gains new function
- neofunctionalization
- expression pattern: regulatory neofunctionalization - subfunctionalization
pseudogenes
common in eukaryote genomes
- derived from functional genes but nonfunctional
-rapid rate of substitutions/ INDELs
- evolve neutrally
- useful for evaluating neutral substitution rate
- eventually deleted or sequence becomes unrecognizable
Features:
- lack of transcription or premature stop codon
- or INDEL that disrupts reading frame
- incorrect splicing
types of selection acting on duplicated genes
positive (KA/KS >1)
- selection promotes fixation of advantageous alleles
- increased sequence divergence
- example pathogen receptors
purifying selection (KA/KS <1)
- selection prevents fixation of deleterious allele
- results in LESS sequence divergence
- ka/ks close to 0= strong
- close to 1=weak or relaxed purifying selection
Chloroplast genomes and phylogenetics
entire genomes are sequenced
- illumina sequencing
- DNA is being tagged and sequenced simultaneously = Barcoding— cost effective
- disadvantage- only half lineage so wont represent original phylogeny
non-functional gene transfer to nucleus
Mitochondria/chloroplast gene transfer to nucleus
- integrates but non-functional
- happens frequently
- gene fragment, single gene, multi-gene region
- many mito and chloroplast pseudogenes in the nuclear genome
functional gene transfer to nucleus
integrated and functional gene that creates product or RNA
- In plants BUT NOT animals
- transfer often occurs by RNA intermediate
- proven by no introns
- direct DNA wouldn’t have correct aa sequence due to c to u RNA editing
- needs to acquire RNA targeting sequence
- from other genes or de novo
- needs regulatory elements for nucleus expression
- Original mito or chloroplast copy is still expressed until nuclear copy becomes functional
plant vs animal mitochondrial genomes
- size
- -Plants: wide range, around 400kb
- animals: 14-17kb
- number of genes
- P: up to 40 protein coding
- -A: 13 protein coding
- gene order in the circular genome
- -P: not conserved
- -A: conserved
- introns
- -P: many
- -A: NONE
- intergenic regions
- -P: large
- -A: little
- rate of nucleotide substitutions
- -P: very low
- -A: very high
Heteroplasmy
some mitochondrial genomes in a cell are normal and some are mutant
- need a threshold to cause disease
Cyto-nuclear interactions
cross-talk btw mitochondrial gene expression and nuclear gene expression so complexes can form
mitochondria do not encode Transcription factors
- some TF regulate both mito and nuclear genes
- some TF regulate other TF that regulate mito genes
- also: TFA–> TFB –> Mitochondrial genes
and TFA–> nuclear encoded mitochondrial genes
codon usage bias
certain codon preferentially used to code for aa
- varies by organism
- can select against nucleotide changes at silent sites
- not all silent sites are neutral evolving
origin of new genes
gene duplication
- retro-position
- exon shuffling
- integration of transposable elements
- gene fusion
- gene fission
- de novo
- horizontal or lateral gene transfer
- change in subcellular localizations
Why is animal mtDNA a desirable molecule for phylogenetic studies
- maternally inheritance
- no recombination
- conserved and less conserved regions
- high mutation rates to compare individuals in a population and within species
why do mtDNA being multi-copy per cell facilitate phylogenetic studies
- multiple copies makes amplification easier
- lack of recombination makes tracing lineages easier
- – universal primers
How is maternal transmission of mtDNA accomplished
male mtDNA in sperm destroyed
- pre and post fertilization
Hydrophobicity of Mitochondrial proteins
hypothesis: long hydrophobic proteins with hydrophobic TMDs are targets for ER by binding SRP
alternate hyp: hydrophobic segments of mt proteins prevent import across the mitochondrial membrane
what can be inferred from ancestral expression pattern and function
neofunctionalization or sub-functionalization
how to evaluate rates of sequence evolution
rates of non-synomous to synomous genes (Ka/Ks ratios)
- higher ratio = positive selection
- less than one= purifying
How can genes undergo neofunctionalization
- mutations in amino acid sequences or structural changes in sequences (INDELs)
if regulatory neofunctionalization - with or without changes in function of protein coding genes
short term consequences of polyploidy
gene silencing + loss of redundant genes/sequences
- chromosome exchanges resulting in loss or doubling in sequences + genome wide rewiring
- subfunctionalization or neofunctionalization
Biased fractionalization
the non-random or biased loss of ancestral genes following allopolyploidy
- more loss from one sister genome compared to other
genome dominance in context of polyploidy
genome wide homology expression bias
- 2 subgroups - more genes from one group expressed than other = genome dominance of expressed subgroup
how can small RNAs and TEs affect expression levels of homeologs and result in one homeolog having lower expression
can silence one homeolog as they are silenced by epigenetic modifications, when insert next to a gene can silence that gene
- density of TEs is higher in regions adjacent to homologs that exhibit lower expression
how does selection and genetic drift act on distribution of TEs
strong deleterious rapidly removed
- no effect on function/fitness - may reach fixation
TE balance btw expression and repression
expression should be sufficient to promote amplification but not so much that leads to fitness disadvantage for host
how can TEs add exons to genes
transduction (addition of exons)
- cryptic splice sites which can cause alternative splicing
