Group activities: Making animal model of human behaviors e.g. Wine preference model in mice

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1 Lecture schedule 3/30 Natural selection of genes and behaviors 4/01 Mouse genetic approaches to behavior 4/06 Gene-knockout and Transgenic technology 4/08 Experimental methods for measuring behaviors 4/13 Chapter 9: The evolution of communication 4/15 Chapter 9: The evolution of communication 4/20 Chapter 10: The evolution of reproductive behaviors 4/22 self study 4/27 self study 4/29 Chapter 10: The evolution of reproductive behaviors 5/04 Chapter 13: The evolution of social behaviors 5/06 Chapter 13: The evolution of social behaviors 5/11 Making animal models for human behaviors-i 5/13 Making animal models for human behaviors-ii

2 Group activities: Making animal model of human behaviors e.g. Wine preference model in mice By using inbred mice, you can get wine preference gene

3 Group activities: Making animal model of human behaviors The Laughing model (Science Apr 1;308(5718):62-3) 1) Mimicking some human behavior: Induction of laughing by tickling rat s trunk 2)What is scientific relevance? On the origin or evolution of 'Ha-Ha

4 Natural selection of genes and behaviors Do genes really evolve? How do you know? Comparison of genes among species

5 Nature Oct 21;431(7011): Finishing the euchromatic sequence of the human genome. International Human Genome Sequencing Consortium. Total human gene: Observer 11 Feb Revealed: the secrete of human behaviour Environment, not genes, key to our acts March 4, 2001 Lives; Quantifiably Normal By THOMAS HAYDEN Scientists were surprised to discover how few genes are encoded by the new sequence -- about 30,000 rather than the expected 80,000 or so

6 Genetics and Behaviors Twin studies (Galton) Ape studies (Gudall) Mouse studies (Tonegawa)

7 Correlation between genetic and behavioral poly morphism Negative selection no selection Positive selection Monkeys Human

8 K A /K S ( dn/ds) compares sequence changes under selection with the background rate a measure of selection pressure averaged across the entire gene KA (dn) the number of nonsynonymous substitution KS (ds) the number of synonymous substitution conserving Negative selection, constraint Diversifying Positive selection K A /K S << 1 purifying selection K A /K S = 1 neutral evolution K A /K S > 1 positive diversifying selection Ka/KS

9 Using the genetic code table, calculate Ka/Ks for the following alignment: ( ( abacus.gene.ucl.ac.uk/software/paml.html) D. melanogaster TTT TCT CAT D. simulans TTC TCC CGT

10 SEMG2 Evolution SEMENOGELIN II Gene involved in sperm motility Potential role in competition among males in promiscuous primate societies Male Females Polyandrous Monoandrous

11 Lineage-specific Ka/Ks values of SEMG2 in primates

12 Rate of molecular evolution of the seminal protein gene SEMG2 correlates with levels of female promiscuity

13 dn/ds

14 Sliding window analysis SEMG2

15 Genetic factor and Brain size

16 Evolution of Nervous System Genes Evolution of Nervous System Genes and Housekeeping Genes in Primates and Rodents(A) Evolutionary rates in primates and rodents.(b) Percentage of genes that evolved with higher Ka/Ks in one or the other mammalian order.the p values indicate the statistical significance of primaterodent d

17 Ka/Ks Distributions of Nervous System Genes The Ka/Ks Distributions of Nervous System Genes and Housekeeping Genes in Primates and Rodents(A) Nervous system-related genes.(b) Housekeeping genes.the p values indicate the statistical significance of primaterodent disparities.

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20 Nervous system genes showing faster evolution in primates

21 Microcephalin and ASPM (abnormal spindle-like, microcephaly associated gene)

22 Evolution of the human brain - divergence Studies show two genes linked to brain size are rapidly evolving in humans Growth of brain size and complexity is likely still going on Accelerated evolution in humans among numerous genes, including microcephalin and ASPM (abnormal spindle-like microcephaly-associated). Both of these genes regulate brain size and were good candidates to look for signatures of selection

23 Evolution of the human brain - polymorphism Variations of microcephalin and ASPM within modern humans For microcephalin, the new variant class emerged about 37,000 years ago and now shows up in about 70 percent of present-day humans. For ASPM, the new variant class arose about 5,800 years ago and now shows up in approximately 30 percent of today s humans Very intense selection pressure that drove up their frequencies in a very brief period of time

24 Fast evolution coincides with modern human historical events Microcephalin variant appears along with the emergence of such traits as art and music, religious practices and sophisticated tool-making techniques, which date back to about 50,000 years ago. The ASPM variant coincides with the oldestknown civilization, Mesopotamia, which dates back to 7000 BC.

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26 The ASPM, asp (abnormal spindle)-like, microcephaly associated gene Isoleucine-Glutamine repeats HUMAN 74 REPEATS MOUSE 61 FLY 24 WORM 2

27 ASPM determine brain size Isoleucine-Glutamine repeats HUMAN 74 REPEATS MOUSE 61 FLY 24 WORM 2

28 Microcephalin and ASPM polymorphism Variation frequency of the two genes, the researchers surveyed more than 1,000 individuals, representing 59 ethnic populations worldwide. For each gene, the scientists identified a large number of haplotypes, or variant copies. They found that one class of haplotypes, called haplogroup D, shows two distinct characteristics. First, they are very young. Second, despite recent emergence they have spread rapidly.

29 Investigate whether positive selection has continued to operate on ASPM since the emergence of anatomically modern humans

30 Implications - IQ? A series of studies suggest that there is some correlation between brain size and intelligence, but with some exceptions. Although, on average, a man s brain is 3 to 4 percent larger than a woman s, both sexes score similarly on IQ tests.

31 Ongoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiens Homozygous null mutations of ASPM cause primary microcephaly Phylogenetic analysis of ASPM has revealed strong positive selection in the primate lineage leading to Homo sapiens, especially in the past 6 million years of hominid evolution in which ASPM acquired about one advantageous amino acid change every 350,000 years.

32 Fast evolution of a speech gene - polymorphism in FoxP2 Forkhead box P2 Researchers in London discovered that around half of the family members - fifteen individuals across three generations - suffered from severe speech and language deficits. Remarkably, the transmission of the disorder from one generation to the next was consistent with autosomal dominant inheritance i.e. mutation of only a single gene on an autosome (non-sex chromosome) acting in a dominant fashion. This is one of the few known examples of Mendelian (monogenic) inheritance for a disorder affecting speech and language skills, which typically have a complex basis involving multiple genetic risk factors.

33 Fast evolution of a speech gene - divergence in FoxP2 Silent and replacement nucleotide substitutions mapped on a phylogeny of primates. Bars represent nucleotide changes. Grey bars indicate amino-acid changes In 75 million years since the divergence of mouse and chimpanzee lineages only one nonsynonymous change has occurred in FOXP2. But in only six million years since the divergence of man and chimpanzee lineages two nonsynonymous changes have occurred in the human lineage

34 Fast evolution of a speech gene - polymorphism in FoxP2 By looking at silent polymorphisms in the gene, Enard et al estimate that the mutations in the FOXP2 in the human lineage occurred between 10,000 and 100,000 years ago. Strong evidence of a selective sweep that was caused by one or both of the mutations in humans, and then they go on to speculate that this change has been critical in the evolution of human speech, perhaps by enabling fine orofacial movements essential to speech

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36 Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene

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