Evolution at the Molecular Level Outline Evolution of genomes Review of various types and effects of mutations How larger genomes evolve through duplication and divergence Molecular archeology based on gene duplication, diversification, and selection 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 original replicator may have been RNA Ribozymes? More complex cells and multicellular organisms appeared > 2 billion years after cellular evolution Earliest cells evolved into three kingdoms of living organisms Archaea and bacteria now contain no introns 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 6 mya – humans diverged from chimpanzees Fig. 21.5 Evolution of Humans Human and chimpanzee genomes 99% similar Karyotypes almost same No significant difference in gene function Divergence may be due to a few thousand isolated genetic changes not yet identified Probably regulatory sequences DNA alterations form the basis of genomic evolution Mutations arise in several ways Replacement of individual nucleotides Deletions / Insertions: 1bp to several Mb Single base substitutions Missense mutations: replace one amino acid codon with another Nonsense mutations: replace amino acid codon with stop codon Splice site mutations: create or remove exon-intron boundaries Frameshift mutations: alter the ORF due to base substitutions Dynamic mutations: changes in the length of tandem repeat elements Effect of mutations on population Neutral mutations are unaffected by agents of selection Deleterious mutations will disappear from a population by selection against the allele Rare mutations increase fitness Genomes grow in size through repeated duplications Some duplications result from transposition Other duplications arise from unequal crossing over Genetic drift and mutations can turn duplications into pseudogenes 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 Fig. 21.10 Basic structure of a gene Fig. 21.11 Genes may elongate by duplication of exons to generate tandem exons that determine tandem functional domains e.g., antibody molecule Fig. 21.12a Exon shuffling may give rise to new genes e.g., tissue plasminogen activator (TPA) Fig. 21.12b Duplications of entire gene can create multigene families Fig. 21.13a Unequal crossing over can expand and contract gene numbers in multigene families Fig. 21.13b Fig. 21.14a Intergenic gene conversion can increase variation among members of a multigene family One gene is changed, the other is not Concerted evolution can lead to gene homogeneity Fig. 21.15 Unequal crossing over Gene conversion Evolution of gene superfamilies 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 Arise by duplication and divergence Evolution of globin superfamily Fig. 21.16 Organisation of globin genes Fig. 21.16 Developmental variation in gene expression a-like chains - z & a b-like chains - e, g, d, b Fig. 21.16 Adult human made of a2b2 – 97%; a2d2 - ~2%; a2g2-~1% (fetal persistence) Gene expression controlled by location Fig. 21.16 e – embryonic yolk sac g – yolk sac & fetal liver b & d – adult bone marrow Evolution of mouse globin superfamily Fig. 21.16 Evolution of mouse globin superfamily Fig. 21.16 The Haemoglobinopathies Thalassemias -Anaemias associated with impaired synthesis of Hb subunits Thalassaemias can arise from different mutations causing a disease of varying severity. a0/b0 thalassaemias – globin chain absent a+/b+ thalassaemias – normal globin chain in reduced amounts a- thalassemias a- thalassemias 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. GENOTYPE a+ a+ a+a+ a+a a+a+ PHENOTYPE Normal Silent carrier a+ a a-thalassaemia trait minor anaemic conditions HbH Hydrops foetalis mild – moderate anaemia foetus survives until around birth a+a a+a+ a a a+a aa aa aa asymptomatic condition. a-thalassaemia – 2 b- thalassemias b- thalassemias 5’ Mutations in b globin cluster are of different types gene deletion transcriptional mutation RNA processing mutations RNA cleavage signal mutations Nonsense & frameshift mutations 3’ Non coding regulatory regions Exons Introns (InterVening Sequences) 3’ cleavage mutant deletion RNA splicing mutant transcription mutant nonsense mutation frameshift insertion frameshift deletion b- thalassemias main genetic mechanisms that contribute to the phenotypic diversity of the b-thalassaemias.