Download lecture 11

Comparative Genomics and
New Evolutionary Biology
10/01/2008
The Genomic Clock
¾ Evolutionary rates of protein families are too different to
support the classic molecular clock concept.
¾ The distributions of the mutation rate among orthologs in two
distant genomes are similar after normalization, suggesting the
existence of a possible genomic clock, which changes linearly
with time.
¾ Thus the evolutionary rate of different sets of orthologs may
differ, the genome-wide distribution remains largely invariant in
shape. Before normalization
After normalization
The major transitions in evolution: a
comparative genomic perspective
¾ There are several transitions during the history of life
1
2
3
4
5
6
7
8
Replicating molecules
to Populations of molecules in
compartments Chromosomes
Independent replicators to Chromosomes
(probably RNA)
RNA as both genes and to DNA as genes, proteins as
enzymes
enzymes
Prokaryotes
to Eukaryotes
Asexual clones
to Sexual populations — evolution
of sex
Protists
to Multicellular organisms —
animals, plants, fungi; evolution
of multicellularity
Solitary individuals
to Colonies with non-reproductive
castes
Primate societies
to Human societies with language,
enabling memes
The Major Transitions in Evolution by John Maynard Smith and Eörs Szathmáry (Oxford University Press, 1995).
The Major transitions in evolution: a comparative
genomic perspective
¾ Comparative genome analyses have provide us a more
concrete understanding of these important transitions, such as
1. From the pure RNA world to RNA-protein life forms;
2. From RNA to DNA as the substance of heredity;
3. From the prokaryotic cell to the eukaryotic cell .
The Last Universal Common Ancestor (LUCA)
and its reconstruction
¾ The molecular evidences of the existence of LUCA: all life
forms
1. share many homologous proteins, in particular, for
information processing (transcription and translation);
2. use almost the same set of genetic code to translate
stored information in their genome into protein;
3. have similar macromolecular assemblies such RNA
polymerase, ribosome and membrane.
The Last Universal Common Ancestor (LUCA)
and its reconstruction
¾ The existence of LUCA has nothing to do with the ideas of the
origin of life, it can be compatible with the panspermia,
exogenesis, multiple origin of life or a primordial pre-LUCA;
¾ One goal of comparative genomics is
1. to derive the rules that have governed gene duplication,
divergence of gene function, gene loss and HGT to shape the
distinct gene repertoire of each major lineage;
2. to use this rules to reconstruct the ancestral genomes that
existed at different stages of evolution including LUCA.
What genes would LUCA have ?
¾ Naively, we might think LUCA contains all the essential genes
shared by the extant genomes, thus reconstruction of the
genome of LUCA become trial by finding all the universal genes.
¾ However, this does not work in its simplest form, because only
65 COGs are universal, and an estimated minimal genome
contains a few hundred genes.
¾ Thus, the universal set of genes are definitely a part of the
LUCA genome, but it should also contain other genes that are
not universally present the modern genomes owing to:
1. parasites and some free-living heterotrophs undergo
substantial gene loss;
2. extensive non-orthologous gene displacement for essential
genes, which also makes reconstruction more difficult.
What genes would LUCA have ?
¾ LUCA must be a chemoautotroph resembling its modern
chemoautotroph, and contained the central metabolic as well as
anabolic pathways and membrane.
¾ All the exiting organisms have similar transcriptional and
translational system suggesting that the LUCA had similar
transcriptional and translational system.
¾ However, some main components of DNA replication systems
in archaea-eukaryotes and bacterial are different. There are
many explanations for this discrepancy:
1. They are too divergent to detect the homology; however
structure analyses refuted this:
archaee-eukarytic primases have palm-like domain,
the bacterial versions have a TOPRIM domain.
What genes would LUCA have ?
2. Existence of two distinct DNA replication systems involves
non-orthologous gene displacement or differential gene loss.
Archaeal-eukaryotic
DNA replication
Archaeal-eukaryotic
Bacterial
DNA replication
DNA replication
Non-orthologous
gene displacement
DNA replication 1
DNA replication 2
DNA replication 1 DNA replication 2
Differential gene loss
What genes would LUCA have ?
¾ However, it’s difficult to make sense to displace the well
developed multi-domain DNA replication complex;
¾ No organism having two DNA replication systems has ever
been found, this also imply that LUCA had a more complicated
DNA replication machinery than its modern descendents.
Archaeal-eukaryotic
DNA replication
Archaeal-eukaryotic
Bacterial
DNA replication
DNA replication
Non-orthologous
gene displacement
DNA replication 1
DNA replication 2
DNA replication 1 DNA replication 2
Differential gene loss
A proposed retrovirus-like genome of LUCA
¾ Instead of containing a DNA-based genome, LUCA might has a
RNA segment-based genome.
A proposed retrovirus-like genome of LUCA
¾ This hypothesis tries to account both for the lack of
conservation of several central components of modern
replication systems and for the presence of some other
conserved components, such as the sliding clamp, clamploader ATPase, and RNAse H, as well as enzymes of DNA
precursor biosynthesis, and the basal transcription and
translation machineries;
¾ This LUCA itself was not modern but rather a transitional form
on the path from the ancient RNA world to the DNA world.
¾ LUCA must have had at least several hundred protein-coding
genes and 30 or so genes for structural RNAs.
A proposed retrovirus-like genome of LUCA
¾ RNA segments of LUCA's genome were of an operon size, i.e.
a typical segment carried three to five genes;
¾ Some operons coding for ribosomal proteins are universally
conserved and must have been inherited from LUCA;
¾ Such a set of genomic segments hardly could segregate with
high accuracy into the daughter protocells during division,
although multiploidy could have increased the likelihood that
each received the complement of essential genes.
¾ Therefore, what we call LUCA inevitably must have been a
collection of protocells with similar but not identical sets of
genome segments.
A brief history of early life
¾ A hypothetical sequence of major events in the evolution of life
from self-replicating RNA to the emergence of modern-type
DNA replication.
Positive
selection
Modern organisms
3.5 billion years
purifying
selection
The transition from prokaryotes to eukaryotes
¾ Even the simplest eukaryotic cell is more complex the most
advanced prokaryotic cell;
¾ The transition from prokaryotes to eukaryotes is one of the
greatest mysteries of life's history.
¾ The endosymbiosis hypothesis: eukaryotes were the result of
uptake of prokaryotes by the protoeukaryote---”you are what
you eat”:
--- mitochondrion is derived from an ancient α-proteobacterium
--- chloroplast is derived from an ancient cyanobacterium
--- cytoskeleton is derived from some ancient bacterium
Actin is likely derived from bacterial cell division proteins
MreB and FtsA; tublin is highly likely derived from FtsB
The transition from prokaryotes to eukaryotes
¾ The eukaryotic proteome is a mix of proteins of apparent
archaeal descent, those that seem to originate from bacteria,
and eukaryote-specific ones.
The origins of the nematode proteins
The transition from prokaryotes to eukaryotes
¾ The genes of archaeal origin code for information processing
system components;
¾ Metabolic enzymes and transporters seem to be largely of
bacterial origin;
¾ At least three distinct scenarios of bacterial gene integration into
the protoeukaryotic genome:
1. Displacement of ancestral, archaeo-eukaryotic genes by
bacterial counterparts (xenologous gene displacement: an
ortholog from a distant lineage (xenolog) displaces the “native”
gene in a given genome );
2. Acquisition of bacterial genes without elimination of the ancestral
archaeo-eukaryotic counterparts so that eukaryotes end up with
both versions of a particular protein;
3. Evolution of new functions by utilization of bacterial proteins
(exaptation).
Conclusions and Outlook
1. Comparative genomics shows that genomes are much more
dynamic, even volatile (on the evolutionary scale) systems than
previously thought;
2. Comparative genomics reaffirms, through numerous illustrations
that evolution is largely a tinker who achieves the best feasible
result by combining, sometimes in haphazard ways, whatever
materials are at hand.
3. Comparative genomics not only vastly complicates the picture of
life's evolution but also provides the information necessary to
resolve the principles and details of this picture.
4. The methods and concrete studies that take us in this direction
are starting to appear but much more remains to be done.