Evolution of Genes and Genomes

1. Evolution of Genes and Genomes Chapter 19

2. The impact of molecular biology on evolutionary biology has been so profound that it is hard to imagine that evolutionary biology could experience further methodological and conceptual shifts of similar magnitude

3. Evolution of Genes and Proteins • Neutral theory of molecular evolution: • DNA sequences and gene evolution are usually considered to be evolving neutrally unless they display the signatures of adaptive evolution Adaptive Evolution and Neutrality The neutral theory states that the vast majority of evolutionary change in genes and chromosomes occurs via mutation followed by random drift, rather than via mutation followed by selection More evidence of adaptive molecular evolution is being found Ex. A recent study suggested that 45% of all amino acid substitutions in Drosophila simulans and Drosophila yakuba have been fixed by natural selection Still the neutral theory is the starting point in any analysis of DNA sequence evolution

4. Evolution of Genes and Proteins • The neutral theory considers polymorphisms within species to be a transient state, one in which a new allele that has arisen by mutation is on its way to either fixation or loss by drift • It also predicts that most change in DNA sequences and proteins will take place in regions that would not affect organismal fitness drastically if modified by mutations • The rate of evolution k of a gene, or a site within a gene, can be expressed as: • k=f0v • where v is the total rate of mutation and f0 is the fraction of mutations that are neutral

5. Evolution of Genes and Proteins Proteins may interact with other proteins, which may be diagrammed as protein interaction networks, in which lines connect pairs of proteins that are known to physically interact with each other • Analysis of these networks have provided evidence that: • There is a negative correlation between the value of k and for a given protein and the number of other proteins with which it interacts • Proteins in the same interaction cluster evolve at more similar rates than expected by chance

6. Evolution of Genes and Proteins Sequence Evolution under Purifying and Positive Selection Purifying Selection Occurs when sequence variants are selected against causing f0<1 and k<v Under strong purifying selection, most nonsynonymous mutations are selected against, but synonymous mutations can still accumulate One index of purifying selection in a protein-coding gene, therefore, is a low ratio of nonsynonymous to synonymous substitutions Positive Selection Positive selection accelerates the accumulation of nonsynonimous mutations over and above the mutation rate If the number of advantageous substitutions in a gene exceeds the number of neutral substitutions, positive Darwinian selection has acted on the gene Rapid evolution at nonsynonimous sites has been documented in a variety of genes including those involved in disease resistance, immune evasion by parasites, and reproduction

7. Evolution of Genes and Proteins Adaptive Molecular Evolution in Primates Adaptive convergent evolution of the enzyme lysozyme which breaks down cell walls Ruminants and colobine monkeys have evolved a modified foregut, in which bacteria digest cellulose. Lysozyme in the rumen enables the animal to digest cell contents Langur’s lysozyme has five amino acid substitutions (compared to other primates) that are also found in the lysozyme of cows. That is, the langur lysozyme is more similar to the lysozyme of the cow, not other primates, at specific amino acid positions

8. Evolution of Genes and Proteins The langurlysozyme underwent an episode of accelerated non synonymous substitution in the ancestral lineage leading to colobines, associated with the evolutionary change in diet from fruit to foliage A similar amino acid substitution in the lysozyme of a leaf-eating bird, the hoatzin, which also has high levels of cellulose-digesting bacteria

9. Evolution of Genes and Proteins Adaptive Evolution across the Genome As the genomes of more and more organisms are completely sequenced, it becomes possible to move beyond description of the evolutionary dynamics of single genes or gene families, and to examine the distribution of selective histories and evolutionary rates across the entire genome There is evidence of adaptive evolution in 873 genes along the human lineage. Several adaptively evolving human genes play key roles in early development, pregnancy, and hearing. It is particularly interesting that many of the adaptively evolving genes are known to cause genetic diseases when mutated

10. Genome Diversity and Evolution Diversity of Genome Structure The structure of genomes across the major branches of life differ widely. VIRAL AND BACTERIAL GENOMES Are models of efficiency, maximizing the speed of genome replication and minimizing unnecessary genes EUKARYOTIC GENOMES Are by comparison large and lumbering, harboring vast regions of noncoding and repeated DNA sequences with unknown functions Although much of this noncoding DNA is unlikely to be “junk” (as was postulated in the early 70s), a typical mammalian genome is by any measure extravagant in its excesses and complexity compared to a bacterial genome

11. Genome Diversity and Evolution Whereas many eukaryotic genes are interrupted by introns, the genomes of Bacteria and Archea have few introns, and these are spliced out by a different mechanism than that used by eukaryotes Introns Early Hypothesis Introns have been present since the common ancestor of all extant life and have simply been lost in those genes and genomes that do not possess them today Supported by some similarity between prokaryotic and eukaryotic introns Introns Late Hypothesis Introns are structures that appeared in large numbers in the eukaryotic genome only recently, long after the prokaryotic-eukaryotic split Supported by the lack of introns in many basal eukaryotes. Also most introns are restricted to specific clades of plants and animals, and can therefore be inferred to have entered eukaryotic genomes relatively recently

12. Genome Diversity and Evolution Eukaryotic genomes contain far more noncoding DNA than prokaryotic genomes do Only 1.5% of the human genome is composed of protein encoding sequences Up to 95% of a typical human gene consists of introns. Moreover there are vast regions of non-coding DNA, much of which may be “selfish DNA” that merely replicates itself and accumulates within genomes However, more than 10% of non-coding DNA is highly conserved between long-diverged species, such as humans and mice, suggesting a function maintained by purifying selection Moreover, many non-coding regions, including introns, are transcribed into RNA sequences such as “microRNAs”. These diverse sequences some represented by as many as 50,000 copies per genome, perform important functions in gene regulation Finally, many eukaryotic genes, unlike prokaryotic genes, are subject to alternative splicing (AS), wherein many (rather than just one) mRNAs are encoded by a single gene

13. Genome Diversity and Evolution Viral and Microbial Genomes: The smallest Genomes • According to life history theory, rapid growth and early reproduction are advantageous in organisms that frequently experience rapid population growth • Thus in organisms such as viruses and bacteria, small genomes are advantageous because they can be copied faster • Indeed, many viruses and bacteria have streamlined their genomes by doing away with many genes. Some of them by exploiting the genomes of their hosts, make do with extremely small and focused genomes • Many viral genomes encode proteins for only 3 functions: • Replication of their genome • Construction of their outer core • Integration of their host genome

14. Genome Diversity and Evolution Ex The RNA genome of HIV is only 9.8Kb, encoding 9 open reading frames

15. Genome Diversity and Evolution The C-value Paradox It was expected that physiologically and behaviorally complex organisms, such as mammals, would have more complex and, and therefore larger, genomes than simpler organisms On a very broad scale this holds true. The smallest genome size in each major group seems to correspond to our impression of complexity Within major groups, such as vertebrates and flowering plants, there seems to be little relationship between genome size and organismal complexity: 0.5 Gbpufferfish, 3Gb human and mouse, 5Gb some salamaders.

16. Genome Diversity and Evolution The C-value is a comparative measure of single-copy DNA content, which contains the majority of functional genes, versus total DNA content, which usually contains a substantial amount of repetitive sequences The lack of correspondence between genome size and phenotypic complexity in eukaryotes was called the C-value paradox, as researchers discovered that not all DNA in a genome carries information that is used during the development and functioning of an organism Genomes contain a great deal of non-informative, highly repetitive, DNA that varies greatly in amount among species

17. Genome Diversity and Evolution Repetitive Sequences and Transposable Elements A substantial fraction of the genome consists of repeated DNA sequences (or satellite DNA) A major source of repeated DNA in human and other mammalian genomes is transposable elements. The genes of most TEs do not contribute to development or function of the host organism; rather, they encode only proteins essential for replication and transposition of the retroelement itself (they are examples of selfish genes) TEs underwent an ancient proliferation 40-50 Mya , and have since then slowed down in their rate of transposition Percentage substitution can be used as a rough proxy for time

18. Genome Diversity and Evolution The effect of a new transposition event on the fitness of the individual bearing it depends largely on where the transposition occurs TEs tend to occur in regions between genes and in introns, probably because those that occur within coding regions often cause deleterious mutations and are eliminated by purifying selection • Transposition can have at least two kinds of genetic effects: • They can cause mutations • The repeated copies of transposable elements in different parts of the genome can provide templates for illegitimate recombination

19. Genome Diversity and Evolution Transposition can lead to adaptive evolution Origin of the invertebrate immune system Each of the huge number of possible antibody proteins is produced by a composite gene consisting of three sequences V, D, J Each V, D, and J segments is flanked by recombination signal sequences (RSS) that direct the joining of the different elements into a single functioning gene

20. The Origin of New Genes The 30,000 different functional genes in mammalian genomes must have evolved from a lower number in the earliest ancestor of living organisms . Presumably, all genes in the human genome ultimately descend from a single gene or set of genes that provided the first programs for life on earth How do such genes arise, and what processes lead to the origin of novel genes?

21. The Origin of New Genes Evolutionary biologists have described several mechanisms by which the genes in a species’ genome have originated, either from pre-existing genes in the same genome or in the genome of a different species: Lateral (Horizontal) Gene Transfer Refers to any process in which an organism incorporates genetic material from another organism without being the offspring of that organism It is now thought that genetic material was often transferred across quite different lineages early in the history of life It has also occurred more recently Ex The eukaryote protist Entamoeba histolytica, which causes over 50 million cases of human dysentery annually, can live anaerobically in the human colon and in tissue abcesses due to fermentation enzymes that most other eukaryotes lack. Some of these fermentation genes were obtained by lateral transfer from a Archaea

22. The Origin of New Genes Exon Shuffling There is a often a close correspondence between the division of a gene into exons and the division of the protein into domains A protein domain is a small segment that can fold into a specific three-dimensional structure independently of other domains. Protein domains frequently have specific functions, although usually they cannot perform these functions completely in the absence of other domains that would together make up a mature protein Many genes evolve by domain accretion, whereby new genes are produced by the addition of the domains to the beginning or ends of ancestral genes The approximate correspondence between gene exons and protein domains in some proteins has lead to the hypothesis of exon shuffling, which states that much of the diversity of genes has evolved as new combinations of exons have been produced by illegitimate (nonhomologous) recombination that occurs in the intervening introns

23. The Origin of New Genes Gene Chimerism and Processed Pseudogenes A chimeric gene is one that consist of pieces derived from two or more different ancestral genes Chimeric genes may arise by exon shuffling and by retrotransposition The first discovered example of this process was the jingwei gene in Drosophila Two copies of Yellow emperor (Ymp) arose by gene duplication An ancestral Adh gene retrotransposed into intron 3 of one of these copies of Ymp After the retroposition event, the exons downstream of the novel Adhexon of Ymp degenerated because the Adh transcript provided a new stop codon

24. The Origin of New Genes Pseudogene Any non-functional DNA sequence that has been derived form a functional gene Processed PseudogenePseudogene that has arisen via retrotransposition of mRNA into cDNA Processed pseudogenes are common in the human and other eukaryotic genomes. In humans there are at least 8000 processed pseudogenes

25. The Origin of New Genes Motif Multiplication and Exon Loss The multiplication of specific motifs can give rise to new genes with new functions The notothenioid fishes of the Southern Ocean are famous for their ability to thrive at ocean temperatures at which most vertebrates’ blood would freeze These fishes have evolved a variety of antifreeze glycoprotein (AFGP) genes encoding short polypeptides that serve to break up ice crystals The evidence suggests that the single triplet amino acid motif in exon 2 of an ancestor of the trypsinogen gene expanded to produce exon 2 of the AFGP gene At some point during or after this event, exons 3-5 of the ancestral trypsinogen gene were lost

26. The Origin of New Genes Gene Duplication and Gene Families One of the most common ways in which new genes originate is by gene duplication, in which new genes arise as copies of pre-existing genes Many genes are member of larger groups of genes, called gene families, that are related to one another by clear common ancestry, and which often have diverse functions that nonetheless have a common theme • The relationship among members of a gene family can be analyzed phylogenetically, both among species and within species • Orthologous Genes • Are found in different species organisms and have diverged from a common ancestral gene by phylogenetic splitting at the organismal level • Paralogous Genes • Originate from a common ancestral gene by gene duplication

27. The Origin of New Genes Many genes get duplicated as part of large chromosomal blocks or large whole genomes Many duplicated genes seem to have diverged at the same time based on comparisons of DNA sequences

28. The Origin of New Genes • Two hypotheses for how the genome was duplicated • Big bang: a major peak in the frequency distribution at 500 mya • Continuous mode: continuous distribution of divergence times

29. The Origin of New Genes Gene families vary greatly in size, from just two members to as many as 800 The size of gene families often coincides with specific adaptations. For example mammals have hundreds of genes that encode olfactory receptor proteins, each of which binds one or a few odorant chemicals

30. Phylogenetic and Adaptive Diversification in Gene Families • Gene Conversion • Duplicate genes may undergo gene conversion, which occurs when sequence information from one locus is transferred unidirectionally to other members of the gene family • The consequence of gene conversion is concerted evolution of the gene family • It results in production of the same gene product from multiple loci, which can be adaptive if large quantities of the product are needed.

31. Phylogenetic and Adaptive Diversification in Gene Families • Selective Fates of Recently Duplicated Genes • Paralogous genes are initially redundant: when gene duplication occurs, two identical copies of a gene suddenly exist within the genome. This oppens the possibility for functional diversification which may occur according to two models: • Neofunctionalization • One of the duplicates retains its original function and the other acquires a new function due to fixation of certain new mutations • Evidence of this process is the rapid accumulation of nonsynonymous substitutions in only one of the recently duplicated copies • Neofunctionalization will occur only if advantageous new mutations occur before one of the duplicates loses function due to fixation of disabling mutations, thus becoming a pseudogene

32. Phylogenetic and Adaptive Diversification in Gene Families • Selective Fates of Recently Duplicated Genes • Subfunctionalization • Each gene duplicate becomes specialized for a subset of the functions originally performed by the ancestral single-copy gene • An ancestral gene had two or more functions and in each paralog complementary mutations are fixed that reduce or eliminate a different function • The paralogs are no longer redundant, so both are preserved by natural selection and may later undergo further functional specialization and evolutionary change

33. Phylogenetic and Adaptive Diversification in Gene Families Selective Fates of Recently Duplicated Genes