Evolution at the Molecular Level

Outline Evolution of genomes Evolution of genomes Review of various types and effects of mutations Review of various types and effects of mutations How larger genomes evolve through duplication and divergence How larger genomes evolve through duplication and divergence Molecular archeology based on gene duplication, diversification, and selection Molecular archeology based on gene duplication, diversification, and selection globin gene family: an example of molecular evolution globin gene family: an example of molecular evolution

Speculations on how the first cell arose The first step to life must have been a replicator molecule The first step to life must have been a replicator molecule The original replicator may have been RNA The original replicator may have been RNA Ribozymes? Ribozymes? More complex cells and multicellular organisms appeared > 2 billion years after cellular evolution More complex cells and multicellular organisms appeared > 2 billion years after cellular evolution

Earliest cells evolved into three kingdoms of living organisms Earliest cells evolved into three kingdoms of living organisms Archaea and bacteria now contain no introns Archaea and bacteria now contain no introns Introns late evolutionary elaboration Introns late evolutionary elaboration Fig. 21.3

Basic body plans of some Burgess shale organisms Many species resulting from metazoan explosion have disappeared Fig. 21.4

Evolution of humans 35 mya – primates 35 mya – primates 6 mya – humans diverged from chimpanzees 6 mya – humans diverged from chimpanzees Fig. 21.5

Evolution of Humans Human and chimpanzee genomes 99% similar Human and chimpanzee genomes 99% similar Karyotypes almost same Karyotypes almost same No significant difference in gene function No significant difference in gene function Divergence may be due to a few thousand isolated genetic changes not yet identified Divergence may be due to a few thousand isolated genetic changes not yet identified Probably regulatory sequences Probably regulatory sequences

DNA alterations form the basis of genomic evolution Mutations arise in several ways Mutations arise in several ways Replacement of individual nucleotides Replacement of individual nucleotides Deletions / Insertions: 1bp to several Mb Deletions / Insertions: 1bp to several Mb Single base substitutions Single base substitutions Missense mutations: replace one amino acid codon with another Missense mutations: replace one amino acid codon with another Nonsense mutations: replace amino acid codon with stop codon Nonsense mutations: replace amino acid codon with stop codon Splice site mutations: create or remove exon-intron boundaries Splice site mutations: create or remove exon-intron boundaries Frameshift mutations: alter the ORF due to base substitutions Frameshift mutations: alter the ORF due to base substitutions Dynamic mutations: changes in the length of tandem repeat elements Dynamic mutations: changes in the length of tandem repeat elements

Effect of mutations on population Neutral mutations are unaffected by agents of selection Neutral mutations are unaffected by agents of selection Deleterious mutations will disappear from a population by selection against the allele Deleterious mutations will disappear from a population by selection against the allele Rare mutations increase fitness Rare mutations increase fitness

Genomes grow in size through repeated duplications Some duplications result from transposition Some duplications result from transposition Other duplications arise from unequal crossing over Other duplications arise from unequal crossing over

Genetic drift and mutations can turn duplications into pseudogenes Genetic drift and mutations can turn duplications into pseudogenes Diversification of a duplicated gene followed by selection can produce a new gene Diversification of a duplicated gene followed by selection can produce a new gene

Genome size increases through duplication of exons, genes, gene families and entire genomes Genome size increases through duplication of exons, genes, gene families and entire genomes Fig

Basic structure of a gene Fig

Genes may elongate by duplication of exons to generate tandem exons that determine tandem functional domains e.g., antibody molecule Fig a

Exon shuffling may give rise to new genes e.g., tissue plasminogen activator (TPA) Fig b

Duplications of entire gene can create multigene families Fig a

Unequal crossing over can expand and contract gene numbers in multigene families Fig b

Intergenic gene conversion can increase variation among members of a multigene family Intergenic gene conversion can increase variation among members of a multigene family One gene is changed, the other is not One gene is changed, the other is not Fig a

Concerted evolution can lead to gene homogeneity Unequal crossing over Gene conversion Fig

Evolution of gene superfamilies Large set of genes divisible into smaller sets, or families Large set of genes divisible into smaller sets, or families Genes in each family more closely rated to each other than to other members of the family Genes in each family more closely rated to each other than to other members of the family Arise by duplication and divergence Arise by duplication and divergence

Evolution of globin superfamily Fig

Organisation of globin genes Fig

Developmental variation in gene expression Fig  -like chains -   -like chains -  Adult human made of     – 97%;     - ~2%;     -~1% (fetal persistence)

Gene expression controlled by location Fig  – embryonic yolk sac  – yolk sac & fetal liver   – adult bone marrow

Evolution of mouse globin superfamily Fig

Evolution of mouse globin superfamily Fig

The Haemoglobinopathies Thalassemias -Anaemias associated with impaired synthesis of Hb subunits Thalassaemias can arise from different mutations causing a disease of varying severity. a 0 /b 0 thalassaemias – globin chain absent a + /b + thalassaemias – normal globin chain in reduced amounts

 thalassemias

GENOTYPEPHENOTYPE a+ a+ a+a+Normal a+a a+a+Silent carrierasymptomatic condition. a-thalassaemia – 2 a+ a a+aa-thalassaemia trait minor anaemic conditions a+a+ a a a+a a aHbHmild – moderate anaemia a a a a Hydrops foetalisfoetus survives until around birth deletion of one or both a globins in an a gene cluster Severity depends on whether the individual has 1,2,3, or 4 missing a globin genes.

 thalassemias

Non coding regulatory regions Exons Introns (InterVening Sequences) 3’ cleavage mutant deletion RNA splicing mutant transcription mutant nonsense mutation frameshift insertion frameshift deletion Mutations in  globin cluster are of different types gene deletion transcriptional mutation RNA processing mutations RNA cleavage signal mutations Nonsense & frameshift mutations

 thalassemias

main genetic mechanisms that contribute to the phenotypic diversity of the  -thalassaemias.